Efficacy of urban road salt reduction strategies on public supply well quality.

Long-term road salt application has increased chloride (Cl-) concentrations in public drinking water wells in many cold climate communities. A range of Best Management Practices (BMPs) have been adopted to mitigate the impact of road deicing compounds on groundwater quality. Chronic increases in chloride levels have been observed in several municipal well fields within the southern Ontario Regional Municipality of Waterloo (RMOW). In response, the RMOW and City of Kitchener implemented a plan to reduce salt application on roads by 25% within the local capture zones of one of the impacted well fields, the Greenbrook Well Field. Here the influence of salt reduction BMPs on subsurface water quality are examined by documenting changes in pore water Cl- concentrations and stored salt mass in vadose zone core samples collected at sites near the well field both before and after the implementation of the BMPs. The data indicate that ~6 years after salt reduction measures were initiated, average pore water Cl- concentration and average cumulative stored chloride mass in the vadose zone had decreased by approximately 60% and 40%, respectively. Groundwater samples collected from shallow monitoring wells installed at each field site showed similar post-BMP reductions in shallow groundwater Cl- concentration (~35%). Long-term (1973-2022) trends in raw water Cl- concentration data from the deeper public drinking water supply wells clearly demonstrate a slow, time-lagged response of the municipal supply wells to the salt reduction BMPs. The combined results suggest that controlled reductions in road salt applications within vulnerable, capture zone regions of public supply wells can reduce the impact of road salt deicing practices on municipal groundwater supplies over time.

Extended pilot test of a cross-injection in situ denitrification system for pre-emptive treatment of municipal well water.

Elevated groundwater nitrate concentrations have been linked to deleterious health and environmental effects. A significant source of the nitrate is nitrogen fertilizers applied to agricultural landscapes. Beneficial Management Practices (BMPs), including the optimization of fertilizer use and selective crop rotations, have proven to be effective in some cases. The city of Woodstock in southern Ontario relies on public wells for all of its municipal supply. Several of the wells have experienced chronic increases in nitrate concentrations exceeding the maximum allowable limit of 10 mg/L N-NO3-. While BMPs are established, an interim reduction plan based on enhanced in situ denitrification (Cross Injection System, CIS) in a 15 m thick zone of high nitrate mass flux within the aquifer zone was evaluated. Based in the results of preliminary acetate injection experiments, a C:N ratio of 2.35, (approximately 260 mg acetate/L), was selected to optimize the denitrification reaction. Injections were performed for six hours a day every day for a period of approximately two months. Dissolved oxygen (DO) and nitrate concentrations recorded over time indicated that reduction of both commenced within a few days of the beginning of the acetate injections and reduced levels were maintained for the remainder of the two-month injection period. Denitrification occurred throughout the profile although nitrate reduction was the highest in the lower groundwater velocity zones. An overall reduction of nitrate of 50% was achieved through the treated section of the aquifer. It is estimated that an upscaled treatment system utilizing a treatment width of only 70 m would be sufficient to reduce the nitrate concentrations to below the drinking water limit demonstrating the potential for the CIS method to functions as an interim groundwater nitrate reduction strategy.

Risk Factors, Hyaluronidase Expression, and Clinical Immunogenicity of Recombinant Human Hyaluronidase PH20, an Enzyme Enabling Subcutaneous Drug Administration.

Multiple FDA-approved and clinical-development stage therapeutics include recombinant human hyaluronidase PH20 (rHuPH20) to facilitate subcutaneous administration. As rHuPH20-reactive antibodies potentially interact with endogenous PH20, we investigated rHuPH20 immunogenicity risk through hyaluronidase tissue expression, predicted B cell epitopes, CD4+ T cell stimulation indices and related these to observed clinical immunogenicity profiles from 18 clinical studies. Endogenous hyaluronidase PH20 expression in humans/mice was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative RT-PCR, and deep RNA-Seq. rHuPH20 potential T cell epitopes were evaluated in silico and confirmed in vitro. Potential B cell epitopes were predicted for rHuPH20 sequence in silico, and binding of polyclonal antibodies from various species tested on a rHuPH20 peptide microarray. Clinical immunogenicity data were collected from 2643 subjects. From 57 human adult and fetal tissues previously screened by RT-PCR, 22 tissue types were analyzed by deep RNA-Seq. Hyaluronidase PH20 messenger RNA expression was detected in adult human testes. In silico analyses of the rHuPH20 sequence revealed nine T cell epitope clusters with immunogenic potential, one cluster was homologous to human leukocyte antigen. rHuPH20 induced T cell activation in 6-10% of peripheral blood mononuclear cell donors. Fifteen epitopes in the rHuPH20 sequence had the potential to cross-react with B cells. The cumulative treatment-induced incidence of anti-rHuPH20 antibodies across clinical studies was 8.8%. Hyaluronidase PH20 expression occurs primarily in adult testes. Low CD4+ T cell activation and B cell cross-reactivity by rHuPH20 suggest weak rHuPH20 immunogenicity potential. Restricted expression patterns of endogenous PH20 indicate low immunogenicity risk of subcutaneous rHuPH20.

Flow diversion in direct carotid-cavernous fistula refractory to multiple coil embolizations: case report and review of the literature.

OBJECTIVES: Direct carotid-cavernous fistulas are high-flow abnormal connections between the carotid artery and cavernous sinus, which are associated with significant morbidity and mortality if left untreated. In addition to endovascular coil embolization, there is an evolving role for alternative stand-alone or adjunctive treatment approaches. We describe a case of flow diversion as an adjunctive treatment approach in a treatment-resistant direct carotid-cavernous fistula and review the literature on the use of flow diversion in this clinical context. MATERIALS AND METHODS: We describe the clinical course, imaging findings, and outcome of a patient who developed a traumatic carotid-cavernous fistula requiring multiple interventions. We also performed an updated literature review of all published cases of flow diversion use in the treatment of direct CCFs. RESULTS: Our patient achieved angiographic cure and significant improvement in symptoms at 6-month follow-up. A total of 53 cases of flow diversion use in direct carotid-cavernous fistulas were identified from a literature search. In one third of cases, flow diversion was used as a stand-alone treatment modality. Angiographic resolution was achieved in 90% of cases at a median follow-up duration of 6 months. One half of reported cases had complete resolution of symptoms and a further third noted clinical improvement in at least some of their symptoms. CONCLUSIONS: There is an emerging role for flow diversion as a safe and effective stand-alone or adjunctive treatment option for direct carotid-cavernous fistulas. Our case further supports a role for flow diversion in treatment-resistant fistulas with high-risk features. As treatment approaches continue to evolve, prospective, randomized data will be needed to establish the role of flow divertors in the hierarchy of available treatments for carotid-cavernous fistulas.

On the adsorption and reactivity of element 114, flerovium.

Flerovium (Fl, element 114) is the heaviest element chemically studied so far. To date, its interaction with gold was investigated in two gas-solid chromatography experiments, which reported two different types of interaction, however, each based on the level of a few registered atoms only. Whereas noble-gas-like properties were suggested from the first experiment, the second one pointed at a volatile-metal-like character. Here, we present further experimental data on adsorption studies of Fl on silicon oxide and gold surfaces, accounting for the inhomogeneous nature of the surface, as it was used in the experiment and analyzed as part of the reported studies. We confirm that Fl is highly volatile and the least reactive member of group 14. Our experimental observations suggest that Fl exhibits lower reactivity towards Au than the volatile metal Hg, but higher reactivity than the noble gas Rn.

Disruption of Hyaluronic Acid in Skeletal Muscle Induces Decreased Voluntary Activity via Chemosensitive Muscle Afferent Sensitization in Male Mice.

PEGPH20, a human recombinant hyaluronidase, has been proposed as a coadjutant to pancreatic cancer chemotherapy. In early trials, patients reported increased widespread muscle pain as the main adverse reaction to PEGPH20. To understand how PEGPH20 caused musculoskeletal pain, we systemically administered PEGPH20 to male mice and measured voluntary wheel activity and pain-related behaviors. These were paired with ex vivo electrophysiology of primary sensory neurons, whole DRG real-time PCR, and immunohistochemistry of hindpaw muscle. PEGPH20 induced significantly lower wheel running, compared with vehicle-treated animals, and decreased mechanical withdrawal thresholds 5 d after PEGPH20 injections. Chemo-sensory muscle afferents showed increased responses to noxious chemical stimulation of their receptive fields (RFs) in the PEGPH20-treated group. This was correlated with upregulation of the NGF receptor TrkA, the transient receptor potential vanilloid type 1 (TRPV1) channel and ATP-sensitive channel P2X3 in the DRG. Immunohistochemistry of hindpaw muscles revealed damage to the muscle architecture and extensive infiltration of the tissue by cells of the myelomonocytic lineage 3 d after PEGPH20 injection. Peripheral macrophage ablation in macrophage Fas-induced apoptosis (MaFIA) mice, however, did not prevent the decreased voluntary activity and instead caused even lower levels of running. These results suggest that disruption of hyaluronic acid (HA) within the muscle extracellular matrix (ECM) sensitizes chemo-nociceptive muscle afferents possibly leading to altered pain-like behaviors. Ablation experiments suggest macrophages are necessary for adequate recovery of voluntary activity after HA disruption. These data support a role for HA and macrophages in tissue integrity and muscle pain development in patients taking PEGPH20.

First Study on Nihonium (Nh, Element 113) Chemistry at TASCA.

Nihonium (Nh, element 113) and flerovium (Fl, element 114) are the first superheavy elements in which the 7p shell is occupied. High volatility and inertness were predicted for Fl due to the strong relativistic stabilization of the closed 7p 1/2 sub-shell, which originates from a large spin-orbit splitting between the 7p 1/2 and 7p 3/2 orbitals. One unpaired electron in the outermost 7p 1/2 sub-shell in Nh is expected to give rise to a higher chemical reactivity. Theoretical predictions of Nh reactivity are discussed, along with results of the first experimental attempts to study Nh chemistry in the gas phase. The experimental observations verify a higher chemical reactivity of Nh atoms compared to its neighbor Fl and call for the development of advanced setups. First tests of a newly developed detection device miniCOMPACT with highly reactive Fr isotopes assure that effective chemical studies of Nh are within reach.

4D-imaging of drip-line radioactivity by detecting proton emission from 54mNi pictured with ACTAR TPC.

Proton radioactivity was discovered exactly 50 years ago. First, this nuclear decay mode sets the limit of existence on the nuclear landscape on the neutron-deficient side. Second, it comprises fundamental aspects of both quantum tunnelling as well as the coupling of (quasi)bound quantum states with the continuum in mesoscopic systems such as the atomic nucleus. Theoretical approaches can start either from bound-state nuclear shell-model theory or from resonance scattering. Thus, proton-radioactivity guides merging these types of theoretical approaches, which is of broader relevance for any few-body quantum system. Here, we report experimental measurements of proton-emission branches from an isomeric state in 54mNi, which were visualized in four dimensions in a newly developed detector. We show that these decays, which carry an unusually high angular momentum, ℓ = 5 and ℓ = 7, respectively, can be approximated theoretically with a potential model for the proton barrier penetration and a shell-model calculation for the overlap of the initial and final wave functions.

Spectroscopy along Flerovium Decay Chains: Discovery of

A nuclear spectroscopy experiment was conducted to study α-decay chains stemming from isotopes of flerovium (element Z=114). An upgraded TASISpec decay station was placed behind the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. The fusion-evaporation reactions ^{48}Ca+^{242}Pu and ^{48}Ca+^{244}Pu provided a total of 32 flerovium-candidate decay chains, of which two and eleven were firmly assigned to ^{286}Fl and ^{288}Fl, respectively. A prompt coincidence between a 9.60(1)-MeV α particle event and a 0.36(1)-MeV conversion electron marked the first observation of an excited state in an even-even isotope of the heaviest man-made elements, namely ^{282}Cn. Spectroscopy of ^{288}Fl decay chains fixed Q_{α}=10.06(1) MeV. In one case, a Q_{α}=9.46(1)-MeV decay from ^{284}Cn into ^{280}Ds was observed, with ^{280}Ds fissioning after only 518 µs. The impact of these findings, aggregated with existing data on decay chains of ^{286,288}Fl, on the size of an anticipated shell gap at proton number Z=114 is discussed in light of predictions from two beyond-mean-field calculations, which take into account triaxial deformation.

Identification of the New Isotope

In an experiment performed at Lawrence Berkeley National Laboratory's 88-inch cyclotron, the isotope ^{244}Md was produced in the ^{209}Bi(^{40}Ar,5n) reaction. Decay properties of ^{244}Md were measured at the focal plane of the Berkeley Gas-filled Separator, and the mass number assignment of A=244 was confirmed with the apparatus for the identification of nuclide A. The isotope ^{244}Md is reported to have one, possibly two, α-decaying states with α energies of 8.66(2) and 8.31(2) MeV and half-lives of 0.4_{-0.1}^{+0.4} and ∼6 s, respectively. Additionally, first evidence of the α decay of ^{236}Bk was observed and is reported.

Hyaluronidase inhibits reactive adipogenesis and inflammation of colon and skin.

In this study we evaluated the role of hyaluronan (HA) in reactive adipogenesis, a local expansion of preadipocytes that provides host defense by release of antimicrobial peptides. We observed that HA accumulated during maturation of adipocytes in vitro and was associated with increased expression of preadipocyte factor 1, zinc finger protein 423, and early B cell factor 1. Although HA is normally abundant in the extracellular matrix, a further increase in HA staining occurred in mice at sites of reactive adipogenesis following injury of colon by dextran sodium sulfate or injury of skin from infection with Staphylococcus aureus. HA also abundantly accumulated around adipocytes seen in the colons of patients with inflammatory bowel disease. This HA was necessary for adipocyte maturation because digestion of HA by administration of soluble hyaluronidase or transgenic expression of hyaluronidase 1 inhibited adipogenesis in vitro and in vivo. Furthermore, hyaluronidase also suppressed inflammation of both skin and colon and decreased antimicrobial peptide expression by developing preadipocytes. This resulted in increased bacterial transit across the epithelial barrier despite decreased tissue injury from inflammation. These observations suggest HA plays an important role in reactive adipogenesis and host defense after injury.

PH20 is not expressed in murine CNS and oligodendrocyte precursor cells.

OBJECTIVE: Expression of Spam1/PH20 and its modulation of high/low molecular weight hyaluronan substrate have been proposed to play an important role in murine oligodendrocyte precursor cell (OPC) maturation in vitro and in normal and demyelinated central nervous system (CNS). We reexamined this using highly purified PH20. METHODS: Steady-state expression of mRNA in OPCs was evaluated by quantitative polymerase chain reaction; the role of PH20 in bovine testicular hyaluronidase (BTH) inhibition of OPC differentiation was explored by comparing BTH to a purified recombinant human PH20 (rHuPH20). Contaminants in commercial BTH were identified and their impact on OPC differentiation characterized. Spam1/PH20 expression in normal and demyelinated mouse CNS tissue was investigated using deep RNA sequencing and immunohistological methods with two antibodies directed against recombinant murine PH20. RESULTS: BTH, but not rHuPH20, inhibited OPC differentiation in vitro. Basic fibroblast growth factor (bFGF) was identified as a significant contaminant in BTH, and bFGF immunodepletion reversed the inhibitory effects of BTH on OPC differentiation. Spam1 mRNA was undetected in OPCs in vitro and in vivo; PH20 immunolabeling was undetected in normal and demyelinated CNS. INTERPRETATION: We were unable to detect Spam1/PH20 expression in OPCs or in normal or demyelinated CNS using the most sensitive methods currently available. Further, "BTH" effects on OPC differentiation are not due to PH20, but may be attributable to contaminating bFGF. Our data suggest that caution be exercised when using some commercially available hyaluronidases, and reports of Spam1/PH20 morphogenic activity in the CNS may be due to contaminants in reagents.

Role of the Δ Resonance in the Population of a Four-Nucleon State in the

The ^{54}Fe nucleus was populated from a ^{56}Fe beam impinging on a Be target with an energy of E/A=500 MeV. The internal decay via γ-ray emission of the 10^{+} metastable state was observed. As the structure of this isomeric state has to involve at least four unpaired nucleons, it cannot be populated in a simple two-neutron removal reaction from the ^{56}Fe ground state. The isomeric state was produced in the low-momentum (-energy) tail of the parallel momentum (energy) distribution of ^{54}Fe, suggesting that it was populated via the decay of the Δ^{0} resonance into a proton. This process allows the population of four-nucleon states, such as the observed isomer. Therefore, it is concluded that the observation of this 10^{+} metastable state in ^{54}Fe is a consequence of the quark structure of the nucleons.

Use of an Artificial Sweetener to Identify Sources of Groundwater Nitrate Contamination.

The artificial sweetener acesulfame (ACE) is a potentially useful tracer of waste water contamination in groundwater. In this study, ACE concentrations were measured in waste water and impacted groundwater at 12 septic system sites in Ontario, Canada. All samples of septic tank effluent (n = 37) had ACE >6 µg/L, all samples of groundwater from the proximal plume zones (n = 93) had ACE >1 µg/L and, almost all samples from the distal plume zones had ACE >2 µg/L. Mean mass ratios of total inorganic nitrogen/ACE at the 12 sites ranged from 680 to 3500 for the tank and proximal plume samples. At five sites, decreasing ratio values in the distal zones indicated nitrogen attenuation. These ratios were applied to three aquifers in Canada that are nitrate-stressed and an urban stream where septic systems are present nearby to estimate the amount of waste water nitrate contamination. At the three aquifer locations that are agricultural, low ACE values (<0.02-0.15 µg/L) indicated that waste water contributed <15% of the nitrate in most samples. In groundwater discharging to the urban stream, much higher ACE values (0.2-11 µg/L) indicated that waste water was the likely source of >50% of the nitrate in most samples. This study confirms that ACE is a powerful tracer and demonstrates its use as a diagnostic tool for establishing whether waste water is a significant contributor to groundwater contamination or not.

Upscaling Point Velocity Measurements to Characterize a Glacial Outwash Aquifer.

Small-scale point velocity probe (PVP)-derived velocities were compared to conventional large-scale velocity estimates from Darcy calculations and tracer tests, and the possibility of upscaling PVP data to match the other velocity estimates was evaluated. Hydraulic conductivity was estimated from grain-size data derived from cores, and single-well response testing or slug tests of onsite wells. Horizontal hydraulic gradients were calculated using 3-point estimators from all of the wells within an extensive monitoring network, as well as by representing the water table as a single best fit plane through the entire network. Velocities determined from PVP testing were generally consistent in magnitude with those from depth specific data collected from multilevel monitoring locations in the tracer test, and similar in horizontal flow direction to the average hydraulic gradient. However, scaling up velocity estimates based on PVP measurements for comparison with site-wide Darcy-based velocities revealed issues that challenge the use of Darcy calculations as a generally applicable standard for comparison. The Darcy calculations were shown to underestimate the groundwater velocities determined both by the PVPs and large-scale tracer testing, in a depth-specific sense and as a site-wide average. Some of this discrepancy is attributable to the selective placement of the PVPs in the aquifer. Nevertheless, this result has important implications for the design of in situ treatment systems. It is concluded that Darcy estimations of velocity should be supplemented with independent assessments for these kinds of applications.

New Short-Lived Isotope

Two short-lived isotopes ^{221}U and ^{222}U were produced as evaporation residues in the fusion reaction ^{50}Ti+^{176}Yb at the gas-filled recoil separator TASCA. An α decay with an energy of E_{α}=9.31(5) MeV and half-life T_{1/2}=4.7(7) µs was attributed to ^{222}U. The new isotope ^{221}U was identified in α-decay chains starting with E_{α}=9.71(5) MeV and T_{1/2}=0.66(14) µs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.

Ultrafast Photodetection in the Quantum Wells of Single AlGaAs/GaAs-Based Nanowires.

We investigate the ultrafast optoelectronic properties of single Al0.3Ga0.7As/GaAs core-shell nanowires. The nanowires contain GaAs-based quantum wells. For a resonant excitation of the quantum wells, we find a picosecond photocurrent which is consistent with an ultrafast lateral expansion of the photogenerated charge carriers. This Dember-effect does not occur for an excitation of the GaAs-based core of the nanowires. Instead, the core exhibits an ultrafast displacement current and a photothermoelectric current at the metal Schottky contacts. Our results uncover the optoelectronic dynamics in semiconductor core-shell nanowires comprising quantum wells, and they demonstrate the possibility to use the low-dimensional quantum well states therein for ultrafast photoswitches and photodetectors.

Demonstration of Confined Electron Gas and Steep-Slope Behavior in Delta-Doped GaAs-AlGaAs Core-Shell Nanowire Transistors.

Strong surface and impurity scattering in III-V semiconductor-based nanowires (NW) degrade the performance of electronic devices, requiring refined concepts for controlling charge carrier conductivity. Here, we demonstrate remote Si delta (δ)-doping of radial GaAs-AlGaAs core-shell NWs that unambiguously exhibit a strongly confined electron gas with enhanced low-temperature field-effect mobilities up to 5 × 10(3) cm(2) V(-1) s(-1). The spatial separation between the high-mobility free electron gas at the NW core-shell interface and the Si dopants in the shell is directly verified by atom probe tomographic (APT) analysis, band-profile calculations, and transport characterization in advanced field-effect transistor (FET) geometries, demonstrating powerful control over the free electron gas density and conductivity. Multigated NW-FETs allow us to spatially resolve channel width- and crystal phase-dependent variations in electron gas density and mobility along single NW-FETs. Notably, dc output and transfer characteristics of these n-type depletion mode NW-FETs reveal excellent drain current saturation and record low subthreshold slopes of 70 mV/dec at on/off ratios >10(4)-10(5) at room temperature.

Stimulating in situ denitrification in an aerobic, highly permeable municipal drinking water aquifer.

A preliminary trial of a cross-injection system (CIS) was designed to stimulate in situ denitrification in an aquifer servicing an urban community in southern Ontario. It was hypothesized that this remedial strategy could be used to reduce groundwater nitrate in the aquifer such that it could remain in use as a municipal supply until the beneficial effects of local reduced nutrient loadings lead to long-term water quality improvement at the wellfield. The CIS application involved injecting a carbon source (acetate) into the subsurface using an injection-extraction well pair positioned perpendicular to the regional flow direction, up-gradient of the water supply wells, with the objective of stimulating native denitrifying bacteria. The pilot remedial strategy was targeted in a high nitrate flux zone within an aerobic and heterogeneous section of the glacial sand and gravel aquifer. Acetate injections were performed at intervals ranging from daily to bi-daily. The carbon additions led to general declines in dissolved oxygen concentrations; decreases in nitrate concentration were localized in aquifer layers where velocities were estimated to be less than 0.5m/day. NO3-(15)N and NO3-(18)O isotope data indicated the nitrate losses were due to denitrification. Relatively little nitrate was removed from groundwater in the more permeable strata, where velocities were estimated to be on the order of 18 m/day or greater. Overall, about 11 percent of the nitrate mass passing through the treatment zone was removed. This work demonstrates that stimulating in situ denitrification in an aerobic, highly conductive aquifer is challenging but achievable. Further work is needed to increase rates of denitrification in the most permeable units of the aquifer.