A preliminary comparison of the sulfur geochemistry between two gas hydrate terranes

We compare the authigenic sulfide mineral geochemistry of two, different gas hydrate terranes: the accretionary wedge of the Cascadia continental margin (offshore Oregon) and the passive margin of the BlakeRidgeregion (offshore southeastern US). We expect diagenetic processes effecting sulfide mineral formation (elemental sulfur, iron monosulfides, and pyrite) within these sediments to respond to differing geologic conditions at each setting. In both settings, methane diffuses upward from gas hydrates to the methane-sulfate interface (SMI), where it is consumed by reaction with sulfate during anaerobic methane oxidation (AMO). This microbially-mediated, diagenetic process produces an interstitial environment conducive to authigenic sulfide mineral formation, so that sulfide minerals tend to be concentrated near the SMI and contain more heavy sulfur (34S). Sulfate reduction occurs simultaneously as sulfate is consumed by microbes utilizing sedimentary organic matter as a foodstuff. In this case, more sulfide mineralization occurs above the SMI, and so that sulfide minerals there should contain more 32S. These competing sulfate-depleting processes potentially produce different vertical distributions of the concentration and sulfur isotopic composition (d34S) of sulfide minerals preserved within the sedimentary record. Preliminary geochemical results from ODP Site 1244 (Cascadia) show a shallower SMI, large concentrations of dissolved sulfide, significant levels of dissolved iron only where dissolved sulfide is low to absent, larger amounts of sulfide sulfur in the sediments, and a similar d34S profile as compared to Blake Ridge sediments. Because methane is consumed by AMO in both settings, we hypothesize that sulfate reduction is responsible for most sulfide mineralization within Cascadia sediments

Tax evasion and exchange equity: a reference-dependent approach

The standard portfolio model of tax evasion with a public good produces the perverse conclusion that when taxpayers perceive the public good to be under-/overprovided, an increase in the tax rate increases/decreases evasion. The author treats taxpayers as thinking in terms of gains and losses relative to an endogenous reference level, which reflects perceived exchange equity between the value of taxes paid and the value of public goods supplied. With these alternative behavioral assumptions, the author overturns the aforementioned result in a direction consistent with the empirical evidence. The author also finds a role for relative income in determining individual responses to a change in the marginal rate of tax

Enhanced hydrogen storage in Ni/Ce composite oxides

The properties of dried (but not calcined) coprecipitated nickel ceria systems have been investigated in terms of their hydrogen emission characteristics following activation in hydrogen. XRD and BET data obtained on the powders show similarities to calcined ceria but it is likely that the majority of the material produced by the coprecipitation process is largely of an amorphous nature. XPS data indicate very little nickel is present on the outermost surface of the particles. Nevertheless, the thermal analytical techniques (TGA, DSC and TPD-MS) indicate that the hydrogen has access to the catalyst present and the nickel is able to generate hydrogen species capable of interacting with the support. Both unactivated and activated materials show two hydrogen emission features, viz. low temperature and high temperature emissions (LTE and HTE, respectively) over the temperature range 50 and 500 °C. A clear effect of hydrogen interaction with the material is that the activated sample not only emits much more hydrogen than the corresponding unactivated one but also at lower temperatures. H2 dissociation occurs on the reduced catalyst surface and the spillover mechanism transfers this active hydrogen into the ceria, possibly via the formation and migration of OH− species. The amount of hydrogen obtained (0.24 wt%) is 10× higher than those observed for calcined materials and would suggest that the amorphous phase plays a critical role in this process. The affiliated emissions of CO and CO2 with that of the HTE hydrogen (and consumption of water) strongly suggests a proportion of the hydrogen emission at this point arises from the water gas shift type reaction. It has not been possible from the present data to delineate between the various hydrogen storage mechanisms reported for ceria

Survival of patients with small cell lung cancer undergoing lung resection in England, 1998–2009

Introduction: Chemotherapy or chemoradiotherapy is the recommended treatment for small cell lung cancer (SCLC), except in stage I disease where clinical guidelines state there may be a role for surgery based on favourable outcomes in case series. Evidence supporting adjuvant chemotherapy in resected SCLC is limited but this is widely offered. Methods: Data on 359 873 patients who were diagnosed with a first primary lung cancer in England between 1998 and 2009 were grouped according to histology (SCLC or non-SCLC (NSCLC)) and whether they underwent a surgical resection. We explored their survival using Kaplan-Meier analysis and Cox regression, adjusting for age, sex, comorbidity and socioeconomic status. Results: The survival of 465 patients with resected SCLC was lower than patients with resected NSCLC (5-year survival 31% and 45%, respectively), but much higher than patients of either group who were not resected (3%). The difference between resected SCLC and NSCLC diminished with time after surgery. Survival was superior for the subgroup of 198 'elective' SCLC cases where the diagnosis was most likely known before resection than for the subgroup of 267 'incidental' cases where the SCLC diagnosis was likely to have been made after resection. Conclusions: These data serve as a natural experiment testing the survival after surgical management of SCLC according to NSCLC principles. Patients with SCLC treated surgically for early stage disease may have survival outcomes that approach those of NSCLC, supporting the emerging clinical practice of offering surgical resection to selected patients with SCLC

Receptor antagonism/agonism can be uncoupled from pharmacoperone activity

Pharmacoperones rescue misrouted mutants of the vasopressin receptor type 2 (V2R) and enable them to traffic to the correct biological locus where they function. Previously, a library of nearly 645,000 structures was interrogated with a high throughput screen; pharmacoperones were identified for V2R mutants with a view toward correcting the underlying mutational defects in nephrogenic diabetes insipidus. In the present study, an orthologous assay was used to evaluate hits from the earlier study. We found no consistent relation between antagonism or agonism and pharmacoperone activity. Active pharmacoperones were identified which had minimal antagonistic activity. This increases the therapeutic reach of these drugs, since virtually all pharmacoperone drugs reported to date were selected from peptidomimetic antagonists. Such mixed-activity drugs have a complex pharmacology limiting their therapeutic utility and requiring their removal prior to stimulation of the receptor with agonist

The Effect of Six Days of Dietary Nitrate Supplementation on Performance in Trained CrossFit Athletes

Background: While it is well established that dietary nitrate reduces the metabolic cost of exercise, recent evidence suggests this effect is maintained 24 h following the final nitrate dose when plasma nitrite levels have returned to baseline. In addition, acute dietary nitrate was recently reported to enhance peak power production. Our purpose was to examine whether chronic dietary nitrate supplementation enhanced peak power 24 h following the final dose and if this impacted performance in a heavily power-dependent sport. Methods: In a double-blind, randomized, crossover design, maximal aerobic capacity, body composition, strength, maximal power (30 s Wingate), endurance (2 km rowing time trial), and CrossFit performance (Grace protocol) were assessed before and after six days of supplementation with nitrate (NO) (8 mmol·potassium nitrate·d−1) or a noncaloric placebo (PL). A 10-day washout period divided treatment conditions. Paired t-tests were utilized to assess changes over time and to compare changes between treatments. Results: Peak Wingate power increased significantly over time with NO (889.17 ± 179.69 W to 948.08 ± 186.80 W; p = 0.01) but not PL (898.08 ± 183.24 W to 905.00 ± 157.23 W; p = 0.75). However, CrossFit performance was unchanged, and there were no changes in any other performance parameters. Conclusion: Consuming dietary nitrate in the potassium nitrate salt form improved peak power during a Wingate test, but did not improve elements of strength or endurance in male CrossFit athletes

Identification of Small-Molecule Inhibitors of Neutral Ceramidase (nCDase) via Target-Based High-Throughput Screening

There is interest in developing inhibitors of human neutral ceramidase (nCDase) because this enzyme plays a critical role in colon cancer. There are currently no potent or clinically effective inhibitors for nCDase reported to date, so we adapted a fluorescence-based enzyme activity method to a high-throughput screening format. We opted to use an assay whereby nCDase hydrolyzes the substrate RBM 14-16, and the addition of NaIO4 acts as an oxidant that releases umbelliferone, resulting in a fluorescent signal. As designed, test compounds that act as ceramidase inhibitors will prevent the hydrolysis of RBM 14-16, thereby decreasing fluorescence. This assay uses a 1536-well plate format with excitation in the blue spectrum of light energy, which could be a liability, so we incorporated a counterscreen that allows for rapid selection against fluorescence artifacts to minimize false-positive hits. The high-throughput screen of >650,000 small molecules found several lead series of hits. Multiple rounds of chemical optimization ensued with improved potency in terms of IC50 and selectivity over counterscreen assays. This study describes the first large-scale high-throughput optical screening assay for nCDase inhibitors that has resulted in leads that are now being pursued in crystal docking studies and in vitro drug metabolism and pharmacokinetics (DMPK).National Cancer Institute https://doi.org/10.13039/100000054Stony Brook Cancer CenterPeer Reviewe