To reduce the release of pharmaceuticals and endocrine disruptors into the aquatic environment or to remove them from wastewater intended for direct or indirect reuse, the application of advanced ...wastewater treatment may be required. In the present study, municipal wastewater effluents were treated with ozone (O3) in a pilot-scale plant consisting of two bubble columns. The investigated effluents, which varied in suspended solids concentrations, comprised an effluent of conventional activated sludge treatment (CAS), the same effluent dosed with 15 mg of TSS L-1 of activated sludge (CAS + SS), and the effluent of a membrane bioreactor pilot plant (MBR). Selected classes of pharmaceuticals were spiked in the wastewater at realistic levels ranging from 0.5 to 5 μg L-1. Samples taken at the inlet and the outlet of the pilot plant were analyzed with liquid chromatography (LC)−electrospray tandem mass spectrometry (MS). Macrolide and sulfonamide antibiotics, estrogens, and the acidic pharmaceuticals diclofenac, naproxen, and indomethacin were oxidized by more than 90−99% for O3 doses ≥ 2 mg L-1 in all effluents. X-ray contrast media and a few acidic pharmaceuticals were only partly oxidized, but no significant differences were observed among the three effluents. These results show that many pharmaceuticals present in wastewater can be efficiently oxidized with O3 and that suspended solids have only a minor influence on the oxidation efficiency of nonsorbing micropollutants.
The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a ...full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5
σ
, for all
δ
CP
values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3
σ
(5
σ
) after an exposure of 5 (10) years, for 50% of all
δ
CP
values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to
sin
2
2
θ
13
to current reactor experiments.
The Deep Underground Neutrino Experiment (DUNE) will be a powerful tool for a variety of physics topics. The high-intensity proton beams provide a large neutrino flux, sampled by a near detector ...system consisting of a combination of capable precision detectors, and by the massive far detector system located deep underground. This configuration sets up DUNE as a machine for discovery, as it enables opportunities not only to perform precision neutrino measurements that may uncover deviations from the present three-flavor mixing paradigm, but also to discover new particles and unveil new interactions and symmetries beyond those predicted in the Standard Model (SM). Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNE’s sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, neutrino trident production, dark matter from both beam induced and cosmogenic sources, baryon number violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach.
► Direct UV photolysis of 3 pharmaceuticals in pure and waste water was investigated. ► Ketoprofen has higher photodegradion kinetics, followed by diclofenac and atenolol. ► MP/UV photodegradation ...products were identified for the 3 compounds. ► Photodegradation pathways were proposed to explain the obtained products. ► The persistent photoproducts were identified for each compound.
Pharmaceutical compounds such as ketoprofen, diclofenac and atenolol are frequently detected at relatively high concentrations in secondary effluents from wastewater treatment plants. Therefore, it is important to assess their transformation kinetics and intermediates in subsequent disinfection processes, such as direct ultraviolet (UV) irradiation. The photodegradation kinetics of these compounds using a medium pressure (MP) lamp was assessed in pure water, as well as in filtered and unfiltered treated wastewater. Ketoprofen had the highest time- and fluence-based rate constants in all experiments, whereas atenolol had the lowest values, which is consistent with the corresponding decadic molar absorption coefficient and quantum yield. The fluence-based rate constants of all compounds were evaluated in filtered and unfiltered wastewater matrices as well as in pure water. Furthermore, transformation products of ketoprofen, diclofenac and atenolol were identified and monitored throughout the irradiation experiments, and photodegradation pathways were proposed for each compound. This enabled the identification of persistent transformation products, which are potentially discharged from WWTP disinfection works employing UV photolysis.
Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing ...use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8
T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.
The Deep Underground Neutrino Experiment (DUNE), a 40-kton underground liquid argon time projection chamber experiment, will be sensitive to the electron-neutrino flavor component of the burst of ...neutrinos expected from the next Galactic core-collapse supernova. Such an observation will bring unique insight into the astrophysics of core collapse as well as into the properties of neutrinos. The general capabilities of DUNE for neutrino detection in the relevant few- to few-tens-of-MeV neutrino energy range will be described. As an example, DUNE’s ability to constrain the
ν
e
spectral parameters of the neutrino burst will be considered.
► Assessment of the validity of selected traces to properly investigate hyporheic zone processes. ► Infiltration velocities are calculated using Darcy’s law, temperature gradients and oscillations. ► ...Infiltration amounts are derived from stable isotopes, chloride, and pharmaceuticals.
Hydrodynamic exchange between surface-water and groundwater was studied at a river located within the Rhine Valley in Germany. Piezometric pressure heads and environmental tracers such as temperature, stable isotopes, chloride, X-ray contrast media, and artificial sweetener were investigated within the hyporheic zone and river water plume. Vertical profiles of environmental tracers were collected using multi-level wells within the neutral up-gradient zone, beneath the river bed, and within the horizontal proximal and distal down-gradient zone. Infiltration velocities were calculated from pressure heads, temperature fluctuations and gradients. The amount of river water within groundwater was estimated from vertical profiles of chloride, stable isotopes, and persistent pharmaceuticals. Profiles of stable isotopes and chloride reveal the existence of down-welling within the shallow hyporheic zone that is generated by river bed irregularities. Due to down-welling an above-average migration of river water into the hyporheic zone establishes even under upward hydraulic pressure gradients. The investigated environmental tracers could not distinctively display short-time-infiltration velocities representative for flood waves, while average infiltration velocities calculated over several months are uniform displayed. Based on vertical temperature profiles the down-gradient migration of the river water plume could be observed even after long periods of effluent conditions and over a distance of 200
m from the river bank. X-ray contrast media and artificial sweeteners were observed in high concentrations within the proximal zone, but were not detected at a distance of 200
m from the river bank. Using temperature as environmental tracer within the hyporheic zone may result in overestimating the migration of pollutants within the river water plume as the process of natural attenuation will be neglected. Furthermore, temperature was not able to display the effect of down-welling. Stable isotopes and chloride were found to be suitable environmental tracers to forecast the release and fate of organic contaminants within the hyporheic zone.
Kinetics and product formation of the anti-epileptic drug carbamazepine (CBZ) were investigated in lab-scale experiments during reactions with ozone and OH radicals. Ozone reacts rapidly with the ...double bond in CBZ, yielding several ozonation products containing quinazoline-based functional groups. The structures for three new oxidation products were elucidated using a combination of mass spectrometric and NMR techniques. The three products were determined to be 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one (BQM), 1-(2-benzaldehyde)-(1H,3H)-quinazoline-2,4-dione (BQD), and 1-(2-benzoic acid)-(1H,3H)-quinazoline-2,4-dione (BaQD). Additional kinetic studies of the ozonation products showed very slow subsequent oxidation kinetics with ozone (second-order rate constants, k O 3 = ∼7 M-1 s-1 and ∼1 M-1 s-1 at pH = 6 for BQM and BQD, respectively). Rate constants for reactions with OH radicals, k OH, were determined as ∼7 × 109 M-1 s-1 for BQM and ∼5 × 109 M-1 s-1 for BQD. Thus, mainly reactions with OH radicals lead to their further oxidation. A kinetic model including ozone and OH radical reactions allows a prediction of the time-dependent product distribution during ozonation of natural waters. In Rhine River water, CBZ spiked at 500 ng/L was completely oxidized by ozone with applied doses ≥0.3 mg/L. To confirm that the two major ozonation products BQM and BQD are produced as a result of the ozonation of a CBZ-containing natural water, Lake Zurich water samples were spiked with CBZ (1 μM, 236 μg/L). The oxidation products were identified via LC-UV. Concentrations of 0.48 and 0.15 μM for BQM and BQD, respectively, were measured for an ozone dose of 1.9 mg/L. BQM and BQD were also identified in ozonated water from a German waterworks containing CBZ in its raw water with 0.07−0.20 μg/L. Currently, there are no data available on the biological effects of the formed oxidation products.
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