Experimental study on the influence of preliminary desiccation on the swelling pressure and hydraulic conductivity of compacted bentonite

In deep geological repositories, compacted bentonites have been proposed for use as barrier materials for isolating nuclear waste. The prevailing thermo-hydro-mechanical boundary conditions in the repositories may affect the swelling capacity and permeability of the compacted bentonites. In this study, the effect of preliminary desiccation on the subsequent hydro-mechanical behaviour (swelling pressure and hydraulic conductivity) of compacted Calcigel bentonite was investigated experimentally at 22°C and 80°C. In the first stage of the test, the compacted specimens were subjected to suction-controlled desiccation at 22°C and 80°C using the vapour-equilibrium technique. After the water content reached equilibrium at a given suction, the axial, radial and volumetric shrinkage strains were measured. Afterwards, constant-volume swelling-pressure tests were performed on the desiccated specimens (second test stage) by saturating the dried specimens with deionized water at 22°C and 80°C. At the end of the swelling-pressure test, the hydraulic conductivities of four saturated specimens were measured at each temperature. The volumetric shrinkage strain of the compacted bentonite during desiccation is controlled by suction instead of temperature. In addition, the preliminary desiccation increases both the swelling pressure and hydraulic conductivity of compacted bentonite, particularly if compacted bentonite undergoes extreme desiccation at an applied suction of >700 MPa

Linkage between swelling pressure, total suction of saturated bentonites and suction of saturating aqueous solutions

In deep geological repositories, compacted bentonites have been proposed for use as barrier materials for isolating nuclear waste. The prevailing hydro-mechanical-chemical boundary conditions in the repositories can affect the swelling capacity of compacted bentonites. The present study examines the linkage between the swelling pressure of saturated bentonites, the total suction of saturated bentonites and the suction of hydrating fluids. An equation describing the linkage between these parameters was derived based on the thermodynamics of soil moisture. To validate the derived relationship, laboratory tests involving constant volume swelling pressure tests and total suction measurements after the swelling pressure tests were carried out on a selected Ca-Mg-rich bentonite. Seven bentonite samples with compaction dry density ranging from 1.20 to 1.83 Mg/m3 were hydrated with deionized water, whereas four samples with a dry density of 1.59 Mg/m3 were hydrated with 0.0001 to 2.0 M CaCl2 solutions. The total suctions of the saturated bentonite and the hydrating fluids were determined by using a chilled-mirror hygrometer. The total suction of the saturated bentonite was found to be affected by the compaction dry density and the suction of the hydrating fluids. The experimental results from the present study and from the literature demonstrated that the total suction of saturated bentonites minus the suction of the hydrating fluids used to saturate bentonites is approximately equal to the swelling pressure of saturated bentonites

The Relation of Environmental Conditions With Charge Structure in Central Argentina Thunderstorms

In this study we explored the environmental conditions hypothesized to induce a dominant charge structure in thunderstorms in the province of Cordoba, Argentina, during the RELAMPAGO-CACTI (Remote sensing of Electrification, Lightning, And Mesoscale/microscale Processes with Adaptive Ground Observations-Clouds, Aerosols, Complex Terrain Interactions) field campaigns. Hypothesized environmental conditions are thought to be related to small warm cloud residence time and warm rain growth suppression, which lead to high cloud liquid water contents in the mixed-phase zone, contributing to positive charging of graupel and anomalous charge structure storms. Data from radiosondes, a cloud condensation nuclei (CCN) ground-based instrument and reanalysis were used to characterize the proximity inflow air of storms with anomalous and normal charge structures. Consistent with the initial hypothesis, anomalous storms had small warm cloud depth caused by dry low-level humidity and low 0&deg;C height. Anomalous storms were associated with lower CCN concentrations than normal storms, an opposite result to the initial expectation. High CAPE is not an important condition for the development of anomalous storms in Argentina, as no clear pattern could be found among the different parameters calculated for updraft proxy that would be consistent with the initial hypothesis. &nbsp;</p

The acid ceramidase/ceramide axis controls parasitemia in Plasmodium yoelii-infected mice by regulating erythropoiesis

Acid ceramidase (Ac) is part of the sphingolipid metabolism and responsible for the degradation of ceramide. As bioactive molecule, ceramide is involved in the regulation of many cellular processes. However, the impact of cell-intrinsic Ac activity and ceramide on the course of Plasmodium infection remains elusive. Here, we use Ac-deficient mice with ubiquitously increased ceramide levels to elucidate the role of endogenous Ac activity in a murine malaria model. Interestingly, ablation of Ac leads to alleviated parasitemia associated with decreased T cell responses in the early phase of Plasmodium yoelii infection. Mechanistically, we identified dysregulated erythropoiesis with reduced numbers of reticulocytes, the preferred host cells of P. yoelii, in Ac-deficient mice. Furthermore, we demonstrate that administration of the Ac inhibitor carmofur to wildtype mice has similar effects on P. yoelii infection and erythropoiesis. Notably, therapeutic carmofur treatment after manifestation of P. yoelii infection is efficient in reducing parasitemia. Hence, our results provide evidence for the involvement of Ac and ceramide in controlling P. yoelii infection by regulating red blood cell development

Cortisol excess in patients with primary aldosteronism impacts on left ventricular hypertrophy

Context Primary aldosteronism (PA) represents the most frequent form of endocrine hypertension. Hyperaldosteronism and hypercortisolism both induce excessive left ventricular hypertrophy (LVH) compared to matched essential hypertensives. In recent studies frequent co-secretion of cortisol and aldosterone has been reported in PA patients. Objective Our aim was to investigate the impact of cortisol co-secretion on left ventricular hypertrophy in PA patients. We determined 24-h excretion of mineralocorticoids and glucocorticoids by gas chromatography-mass spectrometry and assessed cardiac remodeling using echocardiography initially and one year after initiation of treatment for PA. Patients We included 73 patients from the Munich center of the German Conn's registry; 45 with unilateral aldosterone-producing adenoma and 28 with bilateral adrenal hyperplasia. Results At the time of diagnosis, 85% of PA patients showed left ventricular hypertrophy according to left ventricular mass index (LVMI, median 62.4 g/m2.). LVMI correlated positively with total glucocorticoid excretion (r2=0.076, p=0.018) as well as with tetrahydroaldosterone excretion (r2=0.070, p=0.024). Adrenalectomy led to significantly reduced LVMI in aldosterone-producing adenoma (p<0.001) while mineralocorticoid receptor antagonist therapy in bilateral adrenal hyperplasia patients reduced LVMI to a lesser degree (p=0.024). In multivariate analysis, the decrease in LVMI was positively correlated with total glucocorticoid excretion and systolic 24-hour blood pressure, but not with tetrahydroaldosterone excretion. Conclusion Cortisol excess appears to have an additional impact on cardiac remodeling in patients with PA. Treatment of PA by either adrenalectomy or mineralocorticoid receptor antagonist improves LVMI. This effect was most pronounced in patients with high total glucocorticoid excretion

During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes

Tumor-draining lymph nodes (LNs) play a crucial role during cancer spread and in initiation of anti-cancer adaptive immunity. Neutrophils form a substantial population of cells in LNs with poorly understood functions. Here, we demonstrate that, during head and neck cancer (HNC) progression, tumor-associated neutrophils transmigrate to LNs and shape anti-tumor responses in a stage-dependent manner. In metastasis-free stages (N0), neutrophils develop an antigen-presenting phenotype (HLA-DR+CD80+CD86+ICAM1+PD-L1-) and stimulate T cells (CD27+Ki67highPD-1-). LN metastases release GM-CSF and via STAT3 trigger development of PD-L1+ immunosuppressive neutrophils, which repress T cell responses. The accumulation of neutrophils in T cell-rich zones of LNs in N0 constitutes a positive predictor for 5-year survival, while increased numbers of neutrophils in LNs of N1-3 stages predict poor prognosis in HNC. These results suggest a dual role of neutrophils as essential regulators of anti-cancer immunity in LNs and argue for approaches fostering immunostimulatory activity of these cells during cancer therapy

The RELAMPAGO Lightning Mapping Array: Preliminary Scientific Results and Application to GLM Calibration and Validation

During November 2018 through April 2019, an 11-station NASA lightning mapping array (LMA) was installed in the Cordoba region of Argentina, in support of GOES-16 Geostationary Lightning Mapper (GLM) calibration and validation, as well as the Remote sensing of Electrification, Lightning, And Mesoscale/microscale Processes with Adaptive Ground Observations (RELAMPAGO) field campaign. This region of Argentina is well known for frequent, intense thunderstorms and severe weather. The LMA was monitored remotely via the Internet throughout its deployment, but due to bandwidth limitations no real-time data were available. Custom GOES-16 imagery provided by NASA SPoRT assisted with monitoring of thunderstorm cases. Occasional site visits were done to obtain data disks, perform routine maintenance, and troubleshoot problems. During the deployment the network captured lightning in a variety of storm modes, including ordinary and severe multicells, supercells, and mesoscale convective systems. Many examples of normal-polarity thunderstorms, as well as a few examples of anomalously charged thunderstorms, were observed. Long (100+ km) horizontally stratified lightning flashes, as well as lightning in overshooting tops, also were frequently observed. Supporting research radar observations were available through January 2019, with operational radar coverage available after that time. Some cases featured supporting ABI meso scanning. This presentation will report on the LMA deployment in context with the RELAMPAGO field campaign, show results from some representative case studies, and will provide initial comparisons to GLM observations

Urine steroid metabolomics as a diagnostic tool in primary aldosteronism

Primary aldosteronism (PA) causes 5-10% of hypertension cases, but only a minority of patients are currently diagnosed and treated because of a complex, stepwise, and partly invasive workup. We tested the performance of urine steroid metabolomics, the computational analysis of 24-hour urine steroid metabolome data by machine learning, for the identification and subtyping of PA. Mass spectrometry-based multi-steroid profiling was used to quantify the excretion of 34 steroid metabolites in 24-hour urine samples from 158 adults with PA (88 with unilateral PA [UPA] due to aldosterone-producing adenomas [APAs]; 70 with bilateral PA [BPA]) and 65 sex- and age-matched healthy controls. All APAs were resected and underwent targeted gene sequencing to detect somatic mutations associated with UPA. Patients with PA had increased urinary metabolite excretion of mineralocorticoids, glucocorticoids, and glucocorticoid precursors. Urine steroid metabolomics identified patients with PA with high accuracy, both when applied to all 34 or only the three most discriminative steroid metabolites (average areas under the receiver-operating characteristics curve [AUCs-ROC] 0.95-0.97). Whilst machine learning was suboptimal in differentiating UPA from BPA (average AUCs-ROC 0.65-0.73), it readily identified APA cases harbouring somatic KCNJ5 mutations (average AUCs-ROC 0.79-85). These patients showed a distinctly increased urine excretion of the hybrid steroid 18-hydroxycortisol and its metabolite 18-oxo-tetrahydrocortisol, the latter identified by machine learning as by far the most discriminative steroid. In conclusion, urine steroid metabolomics is a non-invasive candidate test for the accurate identification of PA cases and KCNJ5-mutated APAs.</p