Emerging Investigators Series: Pyrolysis Removes Common Microconstituents Triclocarban, Triclosan, and Nonylphenol from Biosolids

Reusing biosolids is vital for the sustainability of wastewater management. Pyrolysis is an anoxic thermal degradation process that can be used to convert biosolids into energy rich py-gas and py-oil, and a beneficial soil amendment, biochar. Batch biosolids pyrolysis (60 minutes) revealed that triclocarban and triclosan were removed (to below quantification limit) at 200 °C and 300 °C, respectively. Substantial removal (\u3e90%) of nonylphenol was achieved at 300 °C as well, but 600 °C was required to remove nonylphenol to below the quantification limit. At 500 °C, the pyrolysis reaction time to remove \u3e90% of microconstituents was less than 5 minutes. Fate studies revealed that microconstituents were both volatilized and thermochemically transformed during pyrolysis; microconstituents with higher vapor pressures were more likely to volatilize and leave the pyrolysis reactor before being transformed than compounds with lower vapor pressures. Reductive dehalogenation products of triclocarban and suspected dehalogenation products of triclosan were identified in py-gas. Application of biosolids-derived biochar to soil in place of biosolids has potential to minimize organic microconstituents discharged to the environment provided appropriate management of py-gas and py-oil

A cycling state that can lead to glassy dynamics in intracellular transport

Power-law dwell times have been observed for molecular motors in living cells, but the origins of these trapped states are not known. We introduce a minimal model of motors moving on a two-dimensional network of filaments, and simulations of its dynamics exhibit statistics comparable to those observed experimentally. Analysis of the model trajectories, as well as experimental particle tracking data, reveals a state in which motors cycle unproductively at junctions of three or more filaments. We formulate a master equation for these junction dynamics and show that the time required to escape from this vortex-like state can account for the power-law dwell times. We identify trends in the dynamics with the motor valency for further experimental validation. We demonstrate that these trends exist in individual trajectories of myosin II on an actin network. We discuss how cells could regulate intracellular transport and, in turn, biological function, by controlling their cytoskeletal network structures locally

Concept and Development of a Potent Topical Corticosteroid

In a rational approach to identify an ultrapotent compound for the treatment of therapy-resistant dermatoses, Weirich's modification of McKenzie's skin vasoconstriction assay (HVK test) has been used as the essential selection criteria. In a primary phase, a quantitative relationship between the HVK activity of 25 derivatives of corticosterone substituted in various positions of the skeleton, and their lipophilicity (log P) was established. The specific lipophilicity-independent interactions were accounted for by the inclusion of 'indicator variables' into the regression analysis. The highly significant results allowed to localize an optimal log P range and to identify the influence of various substituents. In a next phase, the evidence of the first HVK analysis was refined by considering 28 additional compounds. On the basis of the confirmed facts, six 21-chloro-6α-fluoro compounds were specifically synthesized and submitted to dermatopharmacological testing. Finally, CGP 14458 (= 2l-chloro-6α,9-difluoro-11β-hydroxy-16β-methyl-3,20-dioxopregna-1,4-dien-17α-yl propionate) which was predicted to be the most potent representative of these series, whose synthesis is described in detail, showed indeed to be the most effective compound. Clinical trials with this compound – halobetasol propionate/Ultravate® (ulobetasol/Miracorten®) – confirmed its unique efficacy, especially in the treatment of severe, chronic plaque psoriasis

Veno-occlusive disease of the liver in children treated for Wilms tumor

Hepatotoxicity consistent with the clinical diagnosis of veno-occlusive disease (VOD) of the liver has been suspected after conventional anti-cancer chemotherapy in children. To establish the incidence of hepatotoxicity and its relationship with VOD, we analyzed toxicity data obtained on 511 children affected by Wilms tumor and treated according to the SIOP-9 protocol. They all received pre- and postnephrectomy chemotherapy using dactinomycin (AD) and vincristine (VCR) +/- other drugs +/- radiotherapy according to surgical stage and histology. Sixty-four patients suffered at least one episode of hepatotoxicity and 41 satisfied the criteria for a clinical diagnosis of VOD. In this latter group, toxicity occurred during preoperative treatment in 15 patients and was confirmed histopathologically in 9 of the 16 liver biopsies obtained. There was a higher percentage of children aged less than 1 year at diagnosis in the VOD group than in the other patients (24% vs. 11.4%). The degree of liver damage in the younger patients seems important, as suggested by a higher increase in transaminases. VOD developed in 12% of the 68 irradiated children vs. 7% in the non-irradiated group. Statistical analysis showed an increased risk of VOD in younger patients (p < 0.001) and in those receiving radiotherapy (p < 0.001). All patients recovered after 6-180 days using supportive therapy only. (1) 8% of children treated according to the SIOP-9 protocol, developed hepatotoxicity consistent with VOD. Excluding patients who received radiotherapy, the incidence was 6%. These figures are much higher than in earlier reports, though different diagnostic criteria were used. (2) Chemotherapy with AD and VCR seems to be a major cause of VOD. (3) Risk factors are young age and concomitant radiotherapy. (4) VOD does not prejudice positive outcome for these patient

A Reflection on Types

The ability to perform type tests at runtime blurs the line between statically-typed and dynamically-checked languages. Recent developments in Haskell’s type system allow even programs that use reflection to themselves be statically typed, using a type-indexed runtime representation of types called \{}\textit{TypeRep}. As a result we can build dynamic types as an ordinary, statically-typed library, on top of \{}\textit{TypeRep} in an open-world context

Refining lunar impact chronology through high spatial resolution 40Ar/39Ar dating of impact melts

Quantitative constraints on the ages of melt-forming impact events on the Moon are based primarily on isotope geochronology of returned samples. However, interpreting the results of such studies can often be difficult because the provenance region of any sample returned from the lunar surface may have experienced multiple impact events over the course of billions of years of bombardment. We illustrate this problem with new laser microprobe 40Ar/39Ar data for two Apollo 17 impact melt breccias. Whereas one sample yields a straightforward result, indicating a single melt-forming event at ca. 3.83 Ga, data from the other sample document multiple impact melt–forming events between ca. 3.81 Ga and at least as young as ca. 3.27 Ga. Notably, published zircon U/Pb data indicate the existence of even older melt products in the same sample. The revelation of multiple impact events through 40Ar/39Ar geochronology is likely not to have been possible using standard incremental heating methods alone, demonstrating the complementarity of the laser microprobe technique. Evidence for 3.83 Ga to 3.81 Ga melt components in these samples reinforces emerging interpretations that Apollo 17 impact breccia samples include a significant component of ejecta from the Imbrium basin impact. Collectively, our results underscore the need to quantitatively resolve the ages of different melt generations from multiple samples to improve our current understanding of the lunar impact record, and to establish the absolute ages of important impact structures encountered during future exploration missions in the inner Solar System