224 research outputs found
Panels of chemically-modified heparin polysaccharides and natural heparan sulfate saccharides exhibit differences in binding to Slit and Robo, as well as variation between protein binding and cellular activity.
Heparin/ heparan sulfate (HS) glycosaminoglycans are required for Slit-Robo cellular responses. Evidence exists for interactions between each combination of Slit, Robo and heparin/HS and for formation of a ternary complex. Heparin/HS are complex mixtures displaying extensive structural diversity. The relevance of this diversity has been studied to a limited extent using a few select chemically-modified heparins as models of HS diversity. Here we extend these studies by parallel screening of structurally diverse panels of eight chemically-modified heparin polysaccharides and numerous natural HS oligosaccharide chromatographic fractions for binding to both Drosophila Slit and Robo N-terminal domains and for activation of a chick retina axon response to the Slit fragment. Both the polysaccharides and oligosaccharide fractions displayed variability in binding and cellular activity that could not be attributed solely to increasing sulfation, extending evidence for the importance of structural diversity to natural HS as well as model modified heparins. They also displayed differences in their interactions with Slit compared to Robo, with Robo preferring compounds with higher sulfation. Furthermore, the patterns of cellular activity across compounds were different to those for binding to each protein, suggesting that biological outcomes are selectively determined in a subtle manner that does not simply reflect the sum of the separate interactions of heparin/HS with Slit and Robo
Immunomodulation by imiquimod in patients with high-risk primary melanoma.
Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80-100% cure rate of lentigo maligna; however, studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma. After treatment of the primary melanoma biopsy site with placebo or imiquimod cream, we measured immune responses in the treated skin, sentinel lymph nodes (SLNs), and peripheral blood. Treatment of primary melanomas with 5% imiquimod cream was associated with an increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN. Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any increases in CD8+ T cells specifically recognizing HLA-A(*)0201-restricted melanoma epitopes in the peripheral blood. The findings from this small pilot study demonstrate that topical imiquimod treatment results in enhanced local and regional T-cell numbers in both the skin and SLN. Further research into TLR7 immunomodulating pathways as a basis for effective immunotherapy against melanoma in conjunction with surgery is warranted
Development of competences while solving real industrial interdisciplinary problems: a successful cooperation with industry
The development of projects in industrial context constitutes an exceptional opportunity for engineering students to develop competences expected by the labour market. Therefore, the adoption of this type of interaction within engineering curricula is highly recommended, not only at the end of the degree, but also in the previous years. The main purpose of this paper is to present and analyse a Project-Based Learning (PBL) semester in which six teams of Industrial Engineering and Management (IEM) students integrate different areas of knowledge, while solving real problems of five companies, emphasizing the technical solutions developed by the students and the feedback provided by the companies. Students' feedback will be also addressed. The main outcomes of this study reveal that most of the technical solutions lie in areas of Lean applications and ergonomic improvement of workplaces. Companies were very pleased with the results of this type of University-Business Cooperation (UBC).This work was funded by COMPETE-POCI-01-0145-FEDER-007043 and FCT-UID-CEC-00319-2013info:eu-repo/semantics/publishedVersio
Early Release Science of the Exoplanet WASP-39b with JWST NIRSpec G395H
Measuring the abundances of carbon and oxygen in exoplanet atmospheres is
considered a crucial avenue for unlocking the formation and evolution of
exoplanetary systems. Access to an exoplanet's chemical inventory requires
high-precision observations, often inferred from individual molecular
detections with low-resolution space-based and high-resolution ground-based
facilities. Here we report the medium-resolution (R600) transmission
spectrum of an exoplanet atmosphere between 3-5 m covering multiple
absorption features for the Saturn-mass exoplanet WASP-39b, obtained with JWST
NIRSpec G395H. Our observations achieve 1.46x photon precision, providing an
average transit depth uncertainty of 221 ppm per spectroscopic bin, and present
minimal impacts from systematic effects. We detect significant absorption from
CO (28.5) and HO (21.5), and identify SO as the
source of absorption at 4.1 m (4.8). Best-fit atmospheric models
range between 3 and 10x solar metallicity, with sub-solar to solar C/O ratios.
These results, including the detection of SO, underscore the importance of
characterising the chemistry in exoplanet atmospheres, and showcase NIRSpec
G395H as an excellent mode for time series observations over this critical
wavelength range.Comment: 44 pages, 11 figures, 3 tables. Resubmitted after revision to Natur
Early Release Science of the exoplanet WASP-39b with JWST NIRCam
Measuring the metallicity and carbon-to-oxygen (C/O) ratio in exoplanet
atmospheres is a fundamental step towards constraining the dominant chemical
processes at work and, if in equilibrium, revealing planet formation histories.
Transmission spectroscopy provides the necessary means by constraining the
abundances of oxygen- and carbon-bearing species; however, this requires broad
wavelength coverage, moderate spectral resolution, and high precision that,
together, are not achievable with previous observatories. Now that JWST has
commenced science operations, we are able to observe exoplanets at previously
uncharted wavelengths and spectral resolutions. Here we report time-series
observations of the transiting exoplanet WASP-39b using JWST's Near InfraRed
Camera (NIRCam). The long-wavelength spectroscopic and short-wavelength
photometric light curves span 2.0 - 4.0 m, exhibit minimal systematics,
and reveal well-defined molecular absorption features in the planet's spectrum.
Specifically, we detect gaseous HO in the atmosphere and place an upper
limit on the abundance of CH. The otherwise prominent CO feature at 2.8
m is largely masked by HO. The best-fit chemical equilibrium models
favour an atmospheric metallicity of 1-100 solar (i.e., an enrichment
of elements heavier than helium relative to the Sun) and a sub-stellar
carbon-to-oxygen (C/O) ratio. The inferred high metallicity and low C/O ratio
may indicate significant accretion of solid materials during planet formation
or disequilibrium processes in the upper atmosphere.Comment: 35 pages, 13 figures, 3 tables, Nature, accepte
Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab
Early Release Science of the exoplanet WASP-39b with JWST NIRISS
Transmission spectroscopy provides insight into the atmospheric properties
and consequently the formation history, physics, and chemistry of transiting
exoplanets. However, obtaining precise inferences of atmospheric properties
from transmission spectra requires simultaneously measuring the strength and
shape of multiple spectral absorption features from a wide range of chemical
species. This has been challenging given the precision and wavelength coverage
of previous observatories. Here, we present the transmission spectrum of the
Saturn-mass exoplanet WASP-39b obtained using the SOSS mode of the NIRISS
instrument on the JWST. This spectrum spans m in wavelength and
reveals multiple water absorption bands, the potassium resonance doublet, as
well as signatures of clouds. The precision and broad wavelength coverage of
NIRISS-SOSS allows us to break model degeneracies between cloud properties and
the atmospheric composition of WASP-39b, favoring a heavy element enhancement
("metallicity") of the solar value, a sub-solar
carbon-to-oxygen (C/O) ratio, and a solar-to-super-solar potassium-to-oxygen
(K/O) ratio. The observations are best explained by wavelength-dependent,
non-gray clouds with inhomogeneous coverage of the planet's terminator.Comment: 48 pages, 12 figures, 2 tables. Under review at Natur
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Nightside clouds and disequilibrium chemistry on the hot Jupiter WASP-43b
Hot Jupiters are among the best-studied exoplanets, but it is still poorly understood how their chemical composition and cloud properties vary with longitude. Theoretical models predict that clouds may condense on the nightside and that molecular abundances can be driven out of equilibrium by zonal winds. Here we report a phase-resolved emission spectrum of the hot Jupiter WASP-43b measured from 5 μm to 12 μm with the JWST’s Mid-Infrared Instrument. The spectra reveal a large day–night temperature contrast (with average brightness temperatures of 1,524 ± 35 K and 863 ± 23 K, respectively) and evidence for water absorption at all orbital phases. Comparisons with three-dimensional atmospheric models show that both the phase-curve shape and emission spectra strongly suggest the presence of nightside clouds that become optically thick to thermal emission at pressures greater than ~100 mbar. The dayside is consistent with a cloudless atmosphere above the mid-infrared photosphere. Contrary to expectations from equilibrium chemistry but consistent with disequilibrium kinetics models, methane is not detected on the nightside (2σ upper limit of 1–6 ppm, depending on model assumptions). Our results provide strong evidence that the atmosphere of WASP-43b is shaped by disequilibrium processes and provide new insights into the properties of the planet’s nightside clouds. However, the remaining discrepancies between our observations and our predictive atmospheric models emphasize the importance of further exploring the effects of clouds and disequilibrium chemistry in numerical models.Peer reviewe
Nightside clouds and disequilibrium chemistry on the hot Jupiter WASP-43b
Hot Jupiters are among the best-studied exoplanets, but it is still poorly understood how their chemical composition and cloud properties vary with longitude. Theoretical models predict that clouds may condense on the nightside and that molecular abundances can be driven out of equilibrium by zonal winds. Here we report a phase-resolved emission spectrum of the hot Jupiter WASP-43b measured from 5-12 μm with JWST's Mid-Infrared Instrument (MIRI). The spectra reveal a large day-night temperature contrast (with average brightness temperatures of 1524±35 and 863±23 Kelvin, respectively) and evidence for water absorption at all orbital phases. Comparisons with three-dimensional atmospheric models show that both the phase curve shape and emission spectra strongly suggest the presence of nightside clouds which become optically thick to thermal emission at pressures greater than ~100 mbar. The dayside is consistent with a cloudless atmosphere above the mid-infrared photosphere. Contrary to expectations from equilibrium chemistry but consistent with disequilibrium kinetics models, methane is not detected on the nightside (2σ upper limit of 1-6 parts per million, depending on model assumptions)
Photochemically-produced SO in the atmosphere of WASP-39b
Photochemistry is a fundamental process of planetary atmospheres that
regulates the atmospheric composition and stability. However, no unambiguous
photochemical products have been detected in exoplanet atmospheres to date.
Recent observations from the JWST Transiting Exoplanet Early Release Science
Program found a spectral absorption feature at 4.05 m arising from SO
in the atmosphere of WASP-39b. WASP-39b is a 1.27-Jupiter-radii, Saturn-mass
(0.28 M) gas giant exoplanet orbiting a Sun-like star with an equilibrium
temperature of 1100 K. The most plausible way of generating SO in
such an atmosphere is through photochemical processes. Here we show that the
SO distribution computed by a suite of photochemical models robustly
explains the 4.05 m spectral feature identified by JWST transmission
observations with NIRSpec PRISM (2.7) and G395H (4.5). SO
is produced by successive oxidation of sulphur radicals freed when hydrogen
sulphide (HS) is destroyed. The sensitivity of the SO feature to the
enrichment of the atmosphere by heavy elements (metallicity) suggests that it
can be used as a tracer of atmospheric properties, with WASP-39b exhibiting an
inferred metallicity of 10 solar. We further point out that
SO also shows observable features at ultraviolet and thermal infrared
wavelengths not available from the existing observations.Comment: 39 pages, 14 figures, accepted to be published in Natur
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