Relationships between gravity waves observed at Earth's surface and in the stratosphere over the central and eastern United States

Observations of tropospheric gravity waves (GWs) made by the new and extensive USArray Transportable Array (TA) barometric network located east of the Rockies, in the central and eastern United States and of stratospheric (30–40 km above sea level) GWs made by the Atmospheric Infrared Sounder (AIRS) are compared over a 5 year time span from 2010 through 2014. GW detections in the period band from 2 to 6 h made at the Earth's surface during the thunderstorm season from May through August each year exhibit the same broad spatial and temporal patterns as observed at stratospheric altitudes. At both levels, the occurrence frequency of GWs is higher at night than during the day and is highest to the west of the Great Lakes. Statistically significant correlations between the variance of the pressure at the TA, which is a proxy for GWs at ground level, with 8.1 μm brightness temperature measurements from AIRS and rain radar precipitation data, which are both proxies for convective activity, indicate that GWs observed at the TA are related to convective sources. There is little, if any, time lag between the two. Correlations between GWs in the stratosphere and at ground level are weaker, possibly due to the AIRS observational filter effect, but are still statistically significant at nighttime. We conclude that convective activity to the west of the Great Lakes is the dominant source of GWs both at ground level and within the stratosphere

El gallo de Léon

Electron energy-loss spectroscopy (EELS) in combination with scanning transmission electron microscopy ( STEM) reveals that the La enrichment at the surface of cerium-lanthanum solid solutions is an averaged effect and that segregation occurs in a mixed oxide phase. This separation occurs within a crystalline particle, where the dopant-rich phase is located at the surface of the dopant-deficient phase. The limiting structure appears to be a solid solution with a La fraction of x = 0.6 in the bulk and x = 0.75 at the surface. Up to a La fraction of 0.6, this phase will coexist with a lanthanum-type structure in different proportions depending on the dopant amount. STEM-EELS appears to be a powerful technique to clarify the existence of a multiphase system, and it shows that XRF, XPS, and XRD measure averaged results and do not show the phase complexity of the solids

The polo-like kinase 1 inhibitor volasertib synergistically increases radiation efficacy in glioma stem cells.

Background: Despite the availability of hundreds of cancer drugs, there is insufficient data on the efficacy of these drugs on the extremely heterogeneous tumor cell populations of glioblastoma (GBM). Results: The PKIS of 357 compounds was initially evaluated in 15 different GSC lines which then led to a more focused screening of the 21 most highly active compounds in 11 unique GSC lines using HTS screening for cell viability. We further validated the HTS result with the second-generation PLK1 inhibitor volasertib as a single agent and in combination with ionizing radiation (IR). Conclusions: Our results reinforce the potential therapeutic efficacy of volasertib in combination with radiation for the treatment of GBM. Methods: We used high-throughput screening (HTS) to identify drugs, out of 357 compounds in the published Protein Kinase Inhibitor Set, with the greatest efficacy against a panel of glioma stem cells (GSCs), which are representative of the classic cancer genome atlas (TCGA) molecular subtypes. Oncotarget 2018; 9(8):10497-10509

Signatures of technetium oxidation states: a new approach

A general strategy for the determination of Tc oxidation state by new approach involving X-ray absorption near edge spectroscopy (XANES) at the Tc L-3 edge is shown. A comprehensive series of Tc-99 compounds, ranging from oxidation states I to VII, was measured and subsequently simulated within the framework of crystal-field multiplet theory. The observable trends in the absorption edge energy shift in combination with the spectral shape allow for a deeper understanding of complicated Tc coordination chemistry. This approach can be extended to numerous studies of Tc systems as this method is one of the most sensitive methods for accurate Tc oxidation state and ligand characterization

Early flowering as a drought escape mechanism in plants: how can it aid wheat production?

Drought escape (DE) is a classical adaptive mechanism which involves rapid plant development to enable the completion of the full life-cycle prior to a coming drought event. This strategy is widely used in populations of native plants, and is also applicable to cereal crops such as wheat. Early flowering time and a shorter vegetative phase can be very important for wheat production in conditions of terminal drought since this can minimize exposure to dehydration during the sensitive flowering and post-anthesis grain filling periods. A gradual shift toward early flowering has been observed over the last century of wheat breeding in countries with a Mediterranean-type climate and frequent terminal drought. This trend is predicted to continue for wheat production in the coming years in response to global climate warming. The advantage of early flowering wheat is apparent under conditions of impending terminal drought, and modern varieties are significantly more productive due to minimization of the risk associated with drought stress. Under favorable conditions, a short vegetative phase can result in reduced plant biomass due to the reduction in time available for photosynthetic production and seed nutrient accumulation. However, high yield potential has been reported for the development of both shallow and deep roots, representing plasticity in response to drought in combination with the early flowering trait. Wheat productivity can be high both in well-watered and drought-affected field trials, where an efficient strategy of DE was associated with quick growth, yield potential and water use efficiency. Therefore, early flowering provides a promising strategy for the production of advanced drought-adapted wheat cultivars.Yuri Shavrukov, Akhylbek Kurishbayev, Satyvaldy Jatayev, Vladimir Shvidchenko, Lyudmila Zotova, Francois Koekemoer, Stephan de Groot, Kathleen Soole and Peter Langridg

Forskolin-induced Organoid Swelling is Associated with Long-term CF Disease Progression

RATIONALE: Cystic fibrosis (CF) is a monogenic life-shortening disease associated with highly variable individual disease progression which is difficult to predict. Here we assessed the association of forskolin-induced swelling (FIS) of patient-derived organoids (PDO) with long-term CF disease progression in multiple organs and compared FIS with the golden standard biomarker sweat chloride concentration (SCC). METHODS: We retrieved 9-year longitudinal clinical data from the Dutch CF Registry of 173 people with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Individual CFTR function was defined by FIS, measured as the relative size increase of intestinal organoids after stimulation with 0.8 µM forskolin, quantified as area under the curve (AUC). We used linear mixed effect models and multivariable logistic regression to estimate the association of FIS with long-term FEV1pp decline and development of pancreatic insufficiency, CF-related liver disease and diabetes. Within these models, FIS was compared with SCC. RESULTS: FIS was strongly associated with longitudinal changes of lung function, with an estimated difference in annual FEV1pp decline of 0.32% (95%CI: 0.11%-0.54%; p=0.004) per 1000-points change in AUC. Moreover, increasing FIS levels were associated with lower odds of developing pancreatic insufficiency (adjusted OR: 0.18, 95%CI: 0.07-0.46, p<0.001), CF-related liver disease (adjusted OR: 0.18, 95%CI: 0.06-0.54, p=0.002) and diabetes (adjusted OR: 0.34, 95%CI: 0.12-0.97, p=0.044). These associations were absent for SCC. CONCLUSION: This study exemplifies the prognostic value of a PDO-based biomarker within a clinical setting, which is especially important for people carrying rare CFTR mutations with unclear clinical consequences

Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients

Background: Monitoring of immunosuppressive drugs such as everolimus and sirolimus is important in allograft rejection prevention in transplant patients. Dried blood spots (DBS) sampling gives patients the opportunity to sample a drop of blood from a fingerprick at home, which can be sent to the laboratory by mail. Methods: A total of 39 sirolimus and 44 everolimus paired fingerprick DBS and whole blood (WB) samples were obtained from 60 adult transplant patients for method comparison using Passing-Bablok regression. Bias was assessed using Bland-Altman. Two validation limits were pre-defined: limits of analytical acceptance were set at >67% of all paired samples within 20% of the mean of both samples and limits of clinical relevance were set in a multidisciplinary team at >80% of all paired samples within 15% of the mean of both samples. Results: For both sirolimus and everolimus, Passing-Bablok regression showed no differences between WB and DBS with slopes of 0.86 (95% CI slope, 0.72-1.02) and 0.96 (95% CI 0.84-1.06), respectively. Only everolimus showed a significant constant bias of 4%. For both sirolimus and everolimus, limits of analytical acceptance were met (76.9% and 81.8%, respectively), but limits or clinical relevance were not met (77.3% and 61.5%, respectively). Conclusions: Because pre-defined limits of clinical relevance were not met, this DBS sampling method for sirolimus and everolimus cannot replace WB sampling in our center at this time. However, if the clinical setting is compatible with less strict limits for clinical relevance, this DBS method is suitable for clinical application

Evolution of Fe Species During the Synthesis of Over-Exchanged Fe/ZSM5 Obtained by Chemical Vapor Deposition of FeCl3

Abstract The evolution of iron in over-exchanged Fe/ZSM5 prepared via chemical vapor deposition of FeCl 3 was studied at each stage of the synthesis. Different characterization techniques (EXAFS, HR-XANES

PITX2 Modulates Atrial Membrane Potential and the Antiarrhythmic Effects of Sodium-Channel Blockers.

BACKGROUND: Antiarrhythmic drugs are widely used to treat patients with atrial fibrillation (AF), but the mechanisms conveying their variable effectiveness are not known. Recent data suggested that paired like homeodomain-2 transcription factor (PITX2) might play an important role in regulating gene expression and electrical function of the adult left atrium (LA). OBJECTIVES: After determining LA PITX2 expression in AF patients requiring rhythm control therapy, the authors assessed the effects of Pitx2c on LA electrophysiology and the effect of antiarrhythmic drugs. METHODS: LA PITX2 messenger ribonucleic acid (mRNA) levels were measured in 95 patients undergoing thoracoscopic AF ablation. The effects of flecainide, a sodium (Na(+))-channel blocker, and d,l-sotalol, a potassium channel blocker, were studied in littermate mice with normal and reduced Pitx2c mRNA by electrophysiological study, optical mapping, and patch clamp studies. PITX2-dependent mechanisms of antiarrhythmic drug action were studied in human embryonic kidney (HEK) cells expressing human Na channels and by modeling human action potentials. RESULTS: Flecainide 1 μmol/l was more effective in suppressing atrial arrhythmias in atria with reduced Pitx2c mRNA levels (Pitx2c(+/-)). Resting membrane potential was more depolarized in Pitx2c(+/-) atria, and TWIK-related acid-sensitive K(+) channel 2 (TASK-2) gene and protein expression were decreased. This resulted in enhanced post-repolarization refractoriness and more effective Na-channel inhibition. Defined holding potentials eliminated differences in flecainide's effects between wild-type and Pitx2c(+/-) atrial cardiomyocytes. More positive holding potentials replicated the increased effectiveness of flecainide in blocking human Nav1.5 channels in HEK293 cells. Computer modeling reproduced an enhanced effectiveness of Na-channel block when resting membrane potential was slightly depolarized. CONCLUSIONS: PITX2 mRNA modulates atrial resting membrane potential and thereby alters the effectiveness of Na-channel blockers. PITX2 and ion channels regulating the resting membrane potential may provide novel targets for antiarrhythmic drug development and companion therapeutics in AF