RV hypertrophy (RVH) is one of the triggers of RV failure in congenital heart disease (CHD). Therefore, improving our understanding of the cellular and molecular basis of this pathology will help in ...developing strategic therapeutic interventions to enhance patient benefit in the future. This review describes the potential mechanisms that underlie the transition from RVH to RV failure. In particular, it addresses structural and functional remodelling that encompass contractile dysfunction, metabolic changes, shifts in gene expression and extracellular matrix remodelling. Both ischaemic stress and reactive oxygen species production are implicated in triggering these changes and will be discussed. Finally, RV remodelling in response to various CHDs as well as the potential role of biomarkers will be addressed.
Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing nevus. The Hippo pathway, by way of YAP activation, rather than MAP ...kinase, has a role in the oncogenic capacity of GNAQ/11 mutations.
We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant nevus cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation.
For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the nevus cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi.
Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal nevus cells. We hypothesise that GNAQ/11 mutant-driven extracellular mitogenic signalling involving YAP activation leads to accumulation of wild-type nevus cells.
Abstract Objective To report the commencement of cochlear implantation (CI) in children in Northern Nigeria and review the challenges encountered with a view to establishing CI programme. Cases Two ...children with post-meningitic sensorineural hearing loss had standard pre-implantation assessment and cochlear implantation surgery in Nigeria in conjunction with surgeons from another developing country. Post-implantation meningitis was encountered and managed in one of the patients. Post-CI rehabilitation started in a foreign country and continued in our centre after training of our speech therapist. Both patients had improvement in their hearing. Conclusion These showcase successful CI in patients from Sub-Saharan Africa, the challenges included need for development of surgical and post-CI rehabilitation personnel and affordability of the cost of the implant. The support of all the stakeholders needed for commencement of a CI programme was noted.
Aircraft and satellite observations indicate the presence of ppt (ppt ≡ pmol/mol) levels of BrO in the free troposphere with important implications for the tropospheric budgets of ozone, OH, and ...mercury. We can reproduce these observations with the GEOS‐Chem global tropospheric chemistry model by including a broader consideration of multiphase halogen (Br‐Cl) chemistry than has been done in the past. Important reactions for regenerating BrO from its nonradical reservoirs include HOBr + Br−/Cl− in both aerosols and clouds, and oxidation of Br− by ClNO3 and ozone. Most tropospheric BrO in the model is in the free troposphere, consistent with observations and originates mainly from the photolysis and oxidation of ocean‐emitted CHBr3. Stratospheric input is also important in the upper troposphere. Including production of gas phase inorganic bromine from debromination of acidified sea salt aerosol increases free tropospheric Bry by about 30%. We find HOBr to be the dominant gas‐phase reservoir of inorganic bromine. Halogen (Br‐Cl) radical chemistry as implemented here in GEOS‐Chem drives 14% and 11% decreases in the global burdens of tropospheric ozone and OH, respectively, a 16% increase in the atmospheric lifetime of methane, and an atmospheric lifetime of 6 months for elemental mercury. The dominant mechanism for the Br‐Cl driven tropospheric ozone decrease is oxidation of NOx by formation and hydrolysis of BrNO3 and ClNO3.
Key Points
Recent BrO observations are interpreted using a new GEOS‐Chem coupled Br‐Cl simulation
Multiphase oxidation of Br‐ by ozone is critical for maintaining the high observed levels of BrO
Br and Cl lower the global burden of O3 by 14% by increasing NOx loss and shortening the O3 lifetime
Right ventricle (RV) remodelling occurs in neonatal patients born with ventricular septal defect (VSD). The presence of a defect between the two ventricles allows for shunting of blood from the left ...to right side. The resulting RV hypertrophy leads to molecular remodelling which has thus far been largely investigated using right atrial (RA) tissue. In this study we used proteomic and phosphoproteomic analysis in order to determine any difference between the proteomes for RA and RV. Samples were therefore taken from the RA and RV of five infants (0.34 ± 0.05 years, mean ± SEM) with VSD who were undergoing cardiac surgery to repair the defect. Significant differences in protein expression between RV and RA were seen. 150 protein accession numbers were identified which were significantly lower in the atria, whereas none were significantly higher in the atria compared to the ventricle. 19 phosphorylation sites (representing 19 phosphoproteins) were also lower in RA. This work has identified differences in the proteome between RA and RV which reflect differences in contractile activity and metabolism. As such, caution should be used when drawing conclusions based on analysis of the RA and extrapolating to the hypertrophied RV.
RV hypertrophy occurs in neonatal patients born with VSD. Very little is known about how the atria responds to RV hypertrophy, especially at the protein level. Access to tissue from age-matched groups of patients is very rare, and we are in the unique position of being able to get tissue from both the atria and ventricle during reparative surgery of these infants. Our findings will be beneficial to future research into heart chamber malformations in congenital heart defects.
Display omitted
•First proteomic report of right atrium and ventricle from infant VSD patients•Protein expression in the right ventricle tended to be higher than in right atrium.•The differences in protein expression were largely related to metabolism mechanisms.•Very few differences in phosphorylated protein expression
This paper examines the application of artificial neural network (ANN) and boosted regression tree (BRT) methods in air quality modelling. The methods were applied to developing air quality models ...for predicting roadside particle mass concentration (PM
10
, PM
2.5
) and particle number counts (PNC) based on air pollution, traffic and meteorological data from Marylebone Road in London. Elastic net, Lasso and principal components analysis were used as feature selection methods for the ANN models to reduce the number of predictor variables and improve their generalisation. The performance of the ANN with feature selection (ANN hybrid) and the BRT models was evaluated and compared using statistical performance metrics. The performance parameters include root mean square error (RMSE), fraction of prediction within a factor of two of the observation (FAC2), mean bias (MB), mean gross error (MGE), the coefficient of correlation (R) and coefficient of efficiency (CoE) values. The input variables selected by the elastic net produced the best performing ANN models. The ANN hybrid produced models performed only slightly better than the BRT models. The
R
values of the ANN elastic net and BRT models were 0.96 and 0.95 for PM
10
, 0.96 and 0.96 for PM
2.5
and 0.89 and 0.87 for PNC, respectively. Their corresponding CoE values were 0.72 and 0.70 for PM
10
, 0.74 and 0.76 for PM
2.5
and 0.81 and 0.71 for PNC respectively. About 80–99% of all the model predictions are within a factor of two of the observed particle concentrations. The BRT models offer more advantages regarding model interpretation and permit feature selection. Therefore, the study recommends the use of BRT over ANN where the model interpretation is a priority.
The pure-phase BiFeO
3
was obtained in one stage by solution combustion synthesis. The influence of the heat treatment process on the phase composition, magnetic, and optical properties was studied. ...The calcination of the powder led to a decrease in the fraction of the impurity phase from 7 to 1% and an increase in the crystallite size. X-ray diffraction revealed the formation of a pure phase upon heat treatment at 600 °C. The band gap of the samples increases from 1.91 to 2.06 eV with an increase in the crystallite size.
M–H
loops measured at room temperature showed a strong ferromagnetic character. For the initial powder,
M
s
was ~ 1.9 emu/g. The dependence of the magnetic properties on the crystallite size has been established.
TEMPO was selected in 2012 by NASA as the first Earth Venture Instrument, for launch between 2018 and 2021. It will measure atmospheric pollution for greater North America from space using ...ultraviolet and visible spectroscopy. TEMPO observes from Mexico City, Cuba, and the Bahamas to the Canadian oil sands, and from the Atlantic to the Pacific, hourly and at high spatial resolution (~2.1km N/S×4.4km E/W at 36.5°N, 100°W). TEMPO provides a tropospheric measurement suite that includes the key elements of tropospheric air pollution chemistry, as well as contributing to carbon cycle knowledge. Measurements are made hourly from geostationary (GEO) orbit, to capture the high variability present in the diurnal cycle of emissions and chemistry that are unobservable from current low-Earth orbit (LEO) satellites that measure once per day. The small product spatial footprint resolves pollution sources at sub-urban scale. Together, this temporal and spatial resolution improves emission inventories, monitors population exposure, and enables effective emission-control strategies.
TEMPO takes advantage of a commercial GEO host spacecraft to provide a modest cost mission that measures the spectra required to retrieve ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), formaldehyde (H2CO), glyoxal (C2H2O2), bromine monoxide (BrO), IO (iodine monoxide), water vapor, aerosols, cloud parameters, ultraviolet radiation, and foliage properties. TEMPO thus measures the major elements, directly or by proxy, in the tropospheric O3 chemistry cycle. Multi-spectral observations provide sensitivity to O3 in the lowermost troposphere, substantially reducing uncertainty in air quality predictions. TEMPO quantifies and tracks the evolution of aerosol loading. It provides these near-real-time air quality products that will be made publicly available. TEMPO will launch at a prime time to be the North American component of the global geostationary constellation of pollution monitoring together with the European Sentinel-4 (S4) and Korean Geostationary Environment Monitoring Spectrometer (GEMS) instruments.
•TEMPO is under development to collect geostationary air quality measurements.•TEMPO will measure every hour during daylight over greater North America.•TEMPO will have the spatial resolution to measure sub-urban variability.•The mission’s primary data products include tropospheric ozone and related species.•TEMPO’s time-resolved observations form a revolutionary data set for air quality.
Atmospheric pollution measurements from space have been evolving from low-earth-orbits (LEO) to geostationary orbits (GEO), to track the diurnal variation of atmospheric emissions. There are three ...GEO instruments in development. TEMPO is NASA's first Earth Venture Instrument, to be launched during 2018-2021. It will measure atmospheric pollution for greater North America using ultraviolet and visible spectroscopy. The European Sentinel-4 and the South Korean GEMS will measure atmospheric pollution for Europe and Southeast Asia, respectively. In this paper, we describe NASA's TEMPO instrument and we propose a similar instrument in GEO to provide hourly atmospheric pollution measurements for the Middle East at very high spatial resolution. The proposed Middle-East TEMPO instrument will cover Arab Countries, and parts of Asia and Europe. The measurement will include the spectra required to retrieve O3, NO2, SO2, H2CO, C2H2O2, H2O, aerosols, cloud parameters, and UVB radiation.
PDF
