Experimental Quantification of the Variability of the Raindrop Size Distribution at Small Scales

Reliable quantitative precipitation estimation is crucial to better understand and eventually prevent water-related natural hazards (floods, landslides, avalanches, ...). Because rainfall is highly variable in time and space, precipitation monitoring and forecasting is a complex task. In addition, the variability of rainfall at small scales (for instance within the radar pixel) is still poorly understood. Knowledge of the rain drop size distribution (DSD) is of primary concern for precipitation estimation and in particular weather radar. To better understand the variability of the DSD at small scales, a network of optical disdrometers (Parsivel) has been designed and set up. The instruments are fully autonomous in term of power supply and data transmission. The network of 16 disdrometers has been deployed over a typical operational weather radar pixel (1 × 1 km2) in Lausanne, Switzerland, for 16months collecting DSD data at a high temporal resolution (30 s). The sampling uncertainty associated with Parsivel measurements has been quantified for different quantities related to the DSD, using a 15-month data set collected by two collocated disdrometers. Using a geostatistical approach, and in particular variograms, the spatial structure of quantities related to the DSD has been quantified. The analyses have been conducted on 36 rainfall events that have been grouped according to three types of rainfall (i.e., convective, transitional and frontal). It shows a significant variability, i.e., larger than the one induced by the sampling process, of the different quantities of interest. The observed spatial structure is significant for temporal resolution below 30 min from which it is difficult to distinguish between the natural variability and the one induced by the sampling process. The impact of the observed variability of the DSD on radar rainfall estimators is investigated focusing on two different radar power laws (the classical Z-R law for conventional radar and the R-Kdp law for polarimetric radar). The parameters of the power laws are estimated at different spatial scales: at the single station scale, at the aggregate of stations scale (aggregate of point measurements) and at the pixel area scale (average over all the stations). First, it shows clear distinct groups of power law parameters according to the type of rainfall. Moreover, the observed variability of these parameters is significantly larger than the variability induced by the sampling process of the instruments. The observed variability in power law parameters can be responsible for deviation in terms of rain amounts at the single station scale ranging from -5 to +15% the one estimated at the pixel (average) scale. The original contributions in this work are: (1) the design and deployment of an innovative network of autonomous disdrometers Parsivel over a typical operational weather radar pixel (1 km2), (2) the quantification of the sampling uncertainty associated with Parsivel measurements, (3) the quantification of the spatial variability of different quantities related to the DSD within this typical radar pixel and (4) the quantification of the influence of this spatial variability of the DSD on radar rainfall estimation (for conventional and polarimetric radar). For illustration, the results are important: (i) to illustrate the added value of the network of disdrometer that has been designed and the interest for various environmental fields (meteorology, hydrology, risks of water-related natural hazards, ...), (ii) for a better knowledge of the spatial variability of the DSD at different scales which should helps improving radar rainfall estimation, (iii) for the quantification of the errors associated with the extension of relationships derived at a specific location to larger domains (e.g., pixel) and (iv) for the ground validation of numerical weather model

A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor mediating the toxicity and tumor-promoting properties of dioxin. AHR has been reported to be overexpressed and constitutively active in a variety of solid tumors, but few data are currently available concerning its role in thyroid cancer. In this study we quantitatively explored a series of 51 paired-normal and papillary thyroid carcinoma (PTC) tissues for AHR-related genes. We identified an increased AHR expression/activity in PTC, independently from its nuclear dimerization partner and repressor but strictly related to a constitutive active MAPK/ERK pathway. The AHR up-regulation followed by an increased expression of AHR target genes was confirmed by a meta-analysis of published microarray data, suggesting a ligand-independent active AHR pathway in PTC. In-vitro studies using a PTC-derived cell line (BCPAP) and HEK293 cells showed that BRAF(V600E) may directly modulate AHR localization, induce AHR expression and activity in an exogenous ligand-independent manner. The AHR pathway might represent a potential novel therapeutic target for PTC in the clinical practice

Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas.

CONTEXT: Limited screening suggests that three germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are not involved in sporadic pituitary tumorigenesis. Multiple novel mutations of this gene have since been identified in familial isolated pituitary adenoma cohorts. OBJECTIVE: The objective of the study was to undertake full AIP coding sequence screening to assess for the presence of germline and somatic mutations in European Union subjects with sporadic pituitary tumors. DESIGN: The study design was the analysis of DNA from peripheral blood lymphocytes and analysis of exons 1-6 and paraexonic intron sequences of AIP. Multiplex ligation-dependent probe amplification was used to screen separate sporadic pituitary tumor tissue samples for discrete and extensive deletions or mutations of the AIP gene. Setting: The study was conducted in university tertiary referral Clinical Genetics, Molecular Biology, and Endocrinology Departments. RESULTS: In 107 patients [prolactinomas (n =49), nonfunctioning tumors (n = 29), somatotropinomas (n = 26), ACTH-secreting tumors (n = 2), TSH-secreting tumors (n = 1)], no germline mutations of AIP were demonstrated. Among a group of 41 tumor samples from other subjects, a novel AIP mutation (R22X) was found in one sample in which the corresponding allele was deleted; follow-up screening of the patient demonstrated a germline R22X AIP mutation. CONCLUSIONS: AIP mutations do not appear to play a prominent role in sporadic pituitary tumorigenesis in this population of European subjects

Using the raindrop size distribution to quantify the soil detachment rate at the laboratory scale

Rainfall simulators are beneficial tools for studying soil erosion processes and sediment transport for different circumstances and scales. They are useful to better understand soil erosion mechanisms and, therefore, to develop and validate process-based erosion models. Simulators permit experimental replicates for both simple and complex configurations. The 2 m × 6 m EPFL erosion flume is equipped with a hydraulic slope control and a sprinkling system located on oscillating bars 3 m above the surface. It provides a near-uniform spatial rainfall distribution. The intensity of the precipitation can be adjusted by changing the oscillation interval. The flume is filled to a depth of 0.32 m with an agricultural loamy soil. Raindrop detachment is an important process in interrill erosion, the latter varying with the soil properties as well as the raindrop size distribution and drop velocity. Since the soil detachment varies with the kinetic energy of raindrops, an accurate characterization of drop size distribution (DSD, measured, e.g., using a laser disdrometer) can potentially support erosion calculations. Here, a laser disdrometer was used at different rainfall intensities in the EPFL flume to quantify the rainfall event in terms of number of drops, diameter and velocity. At the same time, soil particle motion was measured locally using splash cups. These cups measured the detached material rates into upslope and downslope compartments. In contrast to previously reported splash cup experiments, the cups used in this study were equipped at the top with upside-down funnels, the upper part having the same diameter as the soil sampled at the bottom. This ensured that the soil detached and captured by the device was not re-exposed to rainfall. The experimental data were used to quantify the relationship between the raindrop distribution and the splash-driven sediment transport

Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease

<div><p>Background</p><p>In humans, acromegaly due to a pituitary somatotrophic adenoma is a recognized cause of increased left ventricular (LV) mass. Acromegalic cardiomyopathy is incompletely understood, and represents a major cause of morbidity and mortality. We describe the clinical, echocardiographic and histopathologic features of naturally occurring feline acromegalic cardiomyopathy, an emerging disease among domestic cats.</p><p>Methods</p><p>Cats with confirmed hypersomatotropism (IGF-1>1000ng/ml and pituitary mass; n = 67) were prospectively recruited, as were two control groups: diabetics (IGF-1<800ng/ml; n = 24) and healthy cats without known endocrinopathy or cardiovascular disease (n = 16). Echocardiography was performed in all cases, including after hypersomatotropism treatment where applicable. Additionally, tissue samples from deceased cats with hypersomatotropism, hypertrophic cardiomyopathy and age-matched controls (n = 21 each) were collected and systematically histopathologically reviewed and compared.</p><p>Results</p><p>By echocardiography, cats with hypersomatotropism had a greater maximum LV wall thickness (6.5mm, 4.1–10.1mm) than diabetic (5.9mm, 4.2–9.1mm; Mann Whitney, p<0.001) or control cats (5.2mm, 4.1–6.5mm; Mann Whitney, p<0.001). Left atrial diameter was also greater in cats with hypersomatotropism (16.6mm, 13.0–29.5mm) than in diabetic (15.4mm, 11.2–20.3mm; Mann Whitney, p<0.001) and control cats (14.0mm, 12.6–17.4mm; Mann Whitney, p<0.001). After hypophysectomy and normalization of IGF-1 concentration (n = 20), echocardiographic changes proved mostly reversible. As in humans, histopathology of the feline acromegalic heart was dominated by myocyte hypertrophy with interstitial fibrosis and minimal myofiber disarray.</p><p>Conclusions</p><p>These results demonstrate cats could be considered a naturally occurring model of acromegalic cardiomyopathy, and as such help elucidate mechanisms driving cardiovascular remodeling in this disease.</p></div

Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications.

peer reviewedaudience: researcher, professionalGermline mutations of the aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated PA. To provide further insights into the possible role of AIP in pituitary tumour pathogenesis, the expression of AIP and AHR was determined by real-time RT-PCR and/or immunohistochemistry (IHC) in a large series of PA (n=103), including 17 with AIP mutations (AIP(mut)). Variable levels of AIP and AHR transcripts were detected in all PA, with a low AHR expression (P<0.0001 versus AIP). Cytoplasmic AIP and AHR were detected by IHC in 84.0 and 38.6% of PA respectively, and significantly correlated with each other (P=0.006). Nuclear AHR was detected in a minority of PA (19.7%). The highest AIP expression was observed in somatotrophinomas and non-secreting (NS) PA, and multivariate analysis in somatotrophinomas showed a significantly lower AIP immunostaining in invasive versus non-invasive cases (P=0.019). AIP expression was commonly low in other secreting PA. AIP immunostaining was abolished in a minority of AIP(mut) PA, with a frequent loss of cytoplasmic AHR and no evidence of nuclear AHR. In contrast, AIP overexpression in a subset of NS PA could be accompanied by nuclear AHR immunopositivity. We conclude that down-regulation of AIP and AHR may be involved in the aggressiveness of somatotrophinomas. Overall, IHC is a poorly sensitive tool for the screening of AIP mutations. Data obtained on AHR expression suggest that AHR signalling may be differentially affected according to PA phenotype

Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications.

Germline mutations of the aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated PA. To provide further insights into the possible role of AIP in pituitary tumour pathogenesis, the expression of AIP and AHR was determined by real-time RT-PCR and/or immunohistochemistry (IHC) in a large series of PA (n=103), including 17 with AIP mutations (AIP(mut)). Variable levels of AIP and AHR transcripts were detected in all PA, with a low AHR expression (P<0.0001 versus AIP). Cytoplasmic AIP and AHR were detected by IHC in 84.0 and 38.6% of PA respectively, and significantly correlated with each other (P=0.006). Nuclear AHR was detected in a minority of PA (19.7%). The highest AIP expression was observed in somatotrophinomas and non-secreting (NS) PA, and multivariate analysis in somatotrophinomas showed a significantly lower AIP immunostaining in invasive versus non-invasive cases (P=0.019). AIP expression was commonly low in other secreting PA. AIP immunostaining was abolished in a minority of AIP(mut) PA, with a frequent loss of cytoplasmic AHR and no evidence of nuclear AHR. In contrast, AIP overexpression in a subset of NS PA could be accompanied by nuclear AHR immunopositivity. We conclude that down-regulation of AIP and AHR may be involved in the aggressiveness of somatotrophinomas. Overall, IHC is a poorly sensitive tool for the screening of AIP mutations. Data obtained on AHR expression suggest that AHR signalling may be differentially affected according to PA phenotype

Characterization of Aryl Hydrocarbon Receptor Interacting Protein (AIP) Mutations in Familial Isolated Pituitary Adenoma Families

Familial isolated pituitary adenoma (FIPA) is an autosomal dominant condition with variable genetic background and incomplete penetrance. Germline mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene have been reported in 15-40% of FIPA patients. Limited data are available on the functional consequences of the mutations or regarding the regulation of the AIP gene. We describe a large cohort of FIPA families and characterize missense and silent mutations using minigene constructs, luciferase and beta-galactosidase assays, as well as in silico predictions. Patients with AIP mutations had a lower mean age at diagnosis (23.6+/-11.2 years) than AIP mutation-negative patients (40.4+/-14.5 years). A promoter mutation showed reduced in vitro activity corresponding to lower mRNA expression in patient samples. Stimulation of the protein kinase A-pathway positively regulates the AIP promoter. Silent mutations led to abnormal splicing resulting in truncated protein or reduced AIP expression. A two-hybrid assay of protein-protein interaction of all missense variants showed variable disruption of AIP-phosphodiesterase-4A5 binding. In summary, exonic, promoter, splice-site, and large deletion mutations in AIP are implicated in 31% of families in our FIPA cohort. Functional characterization of AIP changes is important to identify the functional impact of gene sequence variants