Anomalous surface waves from Lop Nor nuclear explosions: Observations and numerical modeling

Surface waves from the Chinese test site of Lop Nor are analyzed using long-period and broadband stations located at regional and teleseismic distances and at different azimuths. For most azimuths, strong Love waves between 0.02 and 0.045 Hz are observed with an amplitude of up to 10 times that of the Rayleigh waves. In addition, an anomalous early Rayleigh wave train is observed at some stations in western Europe. Due to a particularly favorable station and source configuration, it is possible to isolate the areas where the anomalies are created. The high-amplitude Love waves must be attributed to either source effects or path effects immediately north of Lop Nor. The early wave train is shown to be due to a partial energy conversion between Love and Rayleigh waves, probably at the Tornquist Zone. To estimate the possible contribution from surface wave conversions to the observed anomalies, numerical simulations are carried out with the indirect boundary element method. The simulations show that a relatively small variation of crustal thickness can induce Rayleigh to Love wave conversions between 0.02 and 0.1 Hz frequency. The calculated amplitudes of the Love waves are significant (up to 35% of the amplitude of the incoming Rayleigh waves), but they are too small to fit the observed amplitude anomaly. The observed converted waves and the numerical results nevertheless indicate that surface wave conversions can be significant across strong lateral crustal heterogeneities. In particular, the conversions due to changes in crustal thickness are located in the period interval which is routinely used for estimation of Ms

Influence of the seismic noise characteristics on noise correlations in the Baltic shield

International audienceIt has recently been shown that correlations of seismic noise can contain significant information about the Green's function along the station profile. Using an array of 38 temporary broad-band stations located in Finland between 1998 September and 1999 March, we study the resulting 703 noise correlations to understand how they are influenced by the directivity of the noise field. The latter information is obtained through f-k analysis of data from two permanent seismic arrays in Germany and Norway and from a subset of stations of the array in Finland. Both types of analysis confirm that the characteristics of the seismic noise is strongly frequency-dependent. At low frequencies (0.02–0.04 Hz), we observe diffuse noise and/or randomly distributed sources. In contrast, the noise is strongly direction-dependent and not fully diffuse in the intermediate period ranges (0.04–0.25 Hz) which correspond to the first and second microseismic peak, created at the Irish and Scottish coast and the western coast of Norway. In this frequency interval the noise is sufficiently close to a plane wave to introduce systematic errors in group velocities for station pairs which are not parallel to the direction of the dominant incident noise. Phase velocities calculated by slant stack over many traces are however correct, independently of profile direction. In the high-frequency band (0.25–1.0 Hz), the situation is a mix between the low-frequency and the intermediate frequency cases. Average phase velocities and individual group velocities from well-oriented profiles are in excellent agreement with results from Rayleigh wave studies of the area

Crustal structure below Popocat\'epetl Volcano (Mexico) from analysis of Rayleigh waves

An array of ten broadband stations was installed on the Popocat\'epetl volcano (Mexico) for five months between October 2002 and February 2003. 26 regional and teleseismic earthquakes were selected and filtered in the frequency time domain to extract the fundamental mode of the Rayleigh wave. The average dispersion curve was obtained in two steps. Firstly, phase velocities were measured in the period range [2-50] s from the phase difference between pairs of stations, using Wiener filtering. Secondly, the average dispersion curve was calculated by combining observations from all events in order to reduce diffraction effects. The inversion of the mean phase velocity yielded a crustal model for the volcano which is consistent with previous models of the Mexican Volcanic Belt. The overall crustal structure beneath Popocat\'epetl is therefore not different from the surrounding area, and the velocities in the lower crust are confirmed to be relatively low. Lateral variations of the structure were also investigated by dividing the network into four parts and by applying the same procedure to each sub-array. No well-defined anomalies appeared for the two sub-arrays for which it was possible to measure a dispersion curve. However, dispersion curves associated with individual events reveal important diffraction for 6 s to 12 s periods which could correspond to strong lateral variations at 5 to 10 km depth

An intercomparison of models used to simulate the short range atmospheric dispersion and deposition of agricultural ammonia emissions

Ammonia (NH3) emitted into the atmosphere from agricultural sources can have an impact on nearby sensitive ecosystems either through elevated ambient concentrations or dry/wet deposition to vegetation and soil surfaces. Environmental impact assessments are often carried out using short-range atmospheric dispersion models to estimate mean annual atmospheric concentrations and total annual deposition of NH3 at the ecosystem location. A range of different atmospheric dispersion models are used for these assessments depending on the location and experience of the assessors and have not, until now, been compared for these types of assessments. This poster compares and validates concentration predictions of four commonly used models (ADMS v4.11, AERMOD v070262, LADD3 and OPS-st4,5) for dispersion from agricultural sources using hypothetical and real case studie

Biased signaling of lipids and allosteric actions of synthetic molecules for GPR119

AbstractGPR119 is a Gαs-coupled lipid-sensor in the gut, where it mediates release of incretin hormones from the enteroendocrine cells and in pancreatic α-cells, where it releases insulin. Naturally occurring lipids such as monoacylglycerols (MAGs) and N-acylethanolamines (NAEs), like oleoylethanolamide (OEA), activate GPR119, and multiple synthetic ligands have been described. Here, we extend the GPR119 signaling profile to Gαq and Gαi in addition to β-arrestin recruitment and the downstream transcription factors CRE (cAMP response element), SRE (serum response element) and NFAT (nuclear factor of activated T cells). The endogenous OEA and the synthetic AR231453 were full agonists in all pathways except for NFAT, where no ligand-modulation was observed. The potency of AR231453 varied <16-fold (EC50 from 6 to 95nM) across the different signaling pathways, whereas that of OEA varied >175-fold (from 85nM to 15μM) indicating a biased signaling for OEA. The degree of constitutive activity was 1–10%, 10–30% and 30–70% of OEA-induced Emax in Gαi, Gαq and Gαs-driven pathways, respectively. This coincided with the lowest and highest OEA potency observed in Gαi and Gαs-driven pathways, respectively. Incubation for 2h with the 2-MAG-lipase inhibitor JZL84 doubled the constitutive activity, indicating that endogenous lipids contribute to the apparent constitutive activity. Finally, besides being an agonist, AR231453 acted as a positive allosteric modulator of OEA and increased its potency by 54-fold at 100nM AR231453. Our studies uncovering broad and biased signaling, masked constitutive activity by endogenous MAGs, and ago-allosteric properties of synthetic ligands may explain why many GPR119 drug-discovery programs have failed so far

Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer : A Randomized, Double-blind, Placebo-Controlled, Phase II Study

Purpose Cachexia is a multifactorial syndrome, associated with poor survival in patients with cancer, and is influenced by the gut microbiota. We investigated the effects of fecal microbiota transplantation (FMT) on cachexia and treatment response in patients with advanced gastroesophageal cancer. Experimental Design: In a double-blind randomized placebo-controlled trial performed in the Amsterdam University Medical Center, we assigned 24 cachectic patients with metastatic HER2-negative gastroesophageal cancer to either allogenic FMT (healthy obese donor) or autologous FMT, prior to palliative chemotherapy (capecitabine and oxaliplatin). Primary objective was to assess the effect of allogenic FMT on satiety. Secondary outcomes were other features of cachexia, along with disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity. Finally, exploratory analyses were performed on the effect of FMT on gut microbiota composition (metagenomic sequencing) and metabolites (untargeted metabolomics). Results: Allogenic FMT did not improve any of the cachexia outcomes. Patients in the allogenic group (n = 12) had a higher DCR at 12 weeks (P = 0.035) compared with the autologous group (n = 12), longer median OS of 365 versus 227 days [ HR = 0.38; 95% confidence interval (CI), 0.14-1.05; P = 0.057] and PFS of 204 versus 93 days (HR = 0.50; 95% CI, 0.21-1.20; P = 0.092). Patients in the allogenic group showed a significant shift in fecal microbiota composition after FMT (P = 0.010) indicating proper engraftment of the donor microbiota. Conclusions: FMT from a healthy obese donor prior to first-line chemotherapy did not affect cachexia, but may have improved response and survival in patients with metastatic gastroesophageal cancer. These results provide a rational for larger FMT trials.Peer reviewe

Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals

The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17β-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17β-Estradiol, 17α-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds—tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p′-DDT, p,p′-DDE, endosulfan, chlomequat chloride, and ethanol—varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods

Effects of urodilatin on natriuresis in cirrhosis patients with sodium retention

BACKGROUND: Sodium retention and ascites are serious clinical problems in cirrhosis. Urodilatin (URO) is a peptide with paracrine effects in decreasing sodium reabsorption in the distal nephron. Our aim was to investigate the renal potency of synthetic URO on urine sodium excretion in cirrhosis patients with sodium retention and ascites. METHODS: Seven cirrhosis patients with diuretics-resistant sodium retention received a short-term (90 min) infusion of URO in a single-blind, placebo-controlled cross-over study. In the basal state after rehydration the patients had urine sodium excretion < 50 mmol/24 h. RESULTS: URO transiently increased urine sodium excretion from 22 ± 16 μmol/min (mean ± SD) to 78 ± 41 μmol/min (P < 0.05) and there was no effect of placebo (29 ± 14 to 44 ± 32). The increase of URO's second messenger after the receptor, cGMP, was normal. URO had no effect on urine flow or on blood pressure. Most of the patients had highly elevated plasma levels of renin, angiotensin II and aldosterone and URO did not change these. CONCLUSION: The short-term low-dose URO infusion increased the sodium excretion of the patients. The increase was small but systematic and potentially clinically important for such patients. The small response contrasts the preserved responsiveness of the URO receptors. The markedly activated systemic pressor hormones in cirrhosis evidently antagonized the local tubular effects of URO

Cutaneous nociception and neurogenic inflammation evoked by PACAP38 and VIP

Pituitary adenylate cyclase-activating peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) belong to the same secretin–glucagon superfamily and are present in nerve fibers in dura and skin. Using a model of acute cutaneous pain we explored differences in pain perception and vasomotor responses between PACAP38 and VIP in 16 healthy volunteers in a double-blind, placebo-controlled, crossover study. All participants received intradermal injections of 200 pmol PACAP38, 200 pmol VIP and placebo into the volar forearm. Measurements included pain intensity on a visual analog scale (VAS), blood flow by laser Doppler flowmetry, visual flare and wheal. Pain intensities after PACAP38 and VIP were mild and limited to a short time of about 100 s after injection. The area under the VAS-time curve was larger following PACAP38 (P = 0.004) and VIP (P = 0.01) compared to placebo. We found no statistical difference in pain perception between PACAP38 and VIP. Skin blood flow increase, flare and wheal were larger after both PACAP38 (P = 0.011) and VIP (P = 0.001) compared to placebo. VIP induced a considerably larger increase in skin blood flow, flare and wheal than PACAP38 (P = 0.002). In conclusion, we found that peripheral nociceptive cutaneous responses elicited by PACAP38 and VIP are similar in healthy volunteers. This suggests that acute pain and vasomotor responses following intradermal injections of PACAP38 and VIP are primarily mediated by VPAC receptors