E2 strengths and transition radii difference of one-phonon 2+ states of 92Zr from electron scattering at low momentum transfer

Background: Mixed-symmetry 2+ states in vibrational nuclei are characterized by a sign change between dominant proton and neutron valence-shell components with respect to the fully symmetric 2+ state. The sign can be measured by a decomposition of proton and neutron transition radii with a combination of inelastic electron and hadron scattering [C. Walz et al., Phys. Rev. Lett. 106, 062501 (2011)]. For the case of 92Zr, a difference could be experimentally established for the neutron components, while about equal proton transition radii were indicated by the data. Method: Differential cross sections for the excitation of one-phonon 2+ and 3- states in 92Zr have been measured with the (e,e') reaction at the S-DALINAC in a momentum transfer range q = 0.3-0.6 fm^(-1). Results: Transition strengths B(E2;2+_1 -> 0+_1) = 6.18(23), B(E2; 2+_2 -> 0+_1) = 3.31(10) and B(E3; 3-_1 -> 0+_1) = 18.4(11) Weisskopf units are determined from a comparison of the experimental cross sections to quasiparticle-phonon model (QPM) calculations. It is shown that a model-independent plane wave Born approximation (PWBA) analysis can fix the ratio of B(E2) transition strengths to the 2+_(1,2) states with a precision of about 1%. The method furthermore allows to extract their proton transition radii difference. With the present data -0.12(51) fm is obtained. Conclusions: Electron scattering at low momentum transfers can provide information on transition radii differences of one-phonon 2+ states even in heavy nuclei. Proton transition radii for the 2+_(1,2) states in 92Zr are found to be identical within uncertainties. The g.s. transition probability for the mixed-symmetry state can be determined with high precision limited only by the available experimental information on the B(E2; 2+_1 -> 0+_1) value.Comment: 14 pages, 5 figures, submitted to Phys. Rev. C, revised manuscrip

Anti-malarial ozonides OZ439 and OZ609 tested at clinically relevant compound exposure parameters in a novel ring-stage survival assay

BACKGROUND: Drug efficacy against kelch 13 mutant malaria parasites can be determined in vitro with the ring-stage survival assay (RSA). The conventional assay protocol reflects the exposure profile of dihydroartemisinin. METHODS: Taking into account that other anti-malarial peroxides, such as the synthetic ozonides OZ439 (artefenomel) and OZ609, have different pharmacokinetics, the RSA was adjusted to the concentration-time profile of these ozonides in humans and a novel, semi-automated readout was introduced. RESULTS: When tested at clinically relevant parameters, it was shown that OZ439 and OZ609 are active against the Plasmodium falciparum clinical isolate Cam3.I(R539T). CONCLUSION: If the in vitro RSA does indeed predict the potency of compounds against parasites with increased tolerance to artemisinin and its derivatives, then the herein presented data suggest that following drug-pulses of at least 48 h, OZ439 and OZ609 will be highly potent against kelch 13 mutant isolates, such as P. falciparum Cam3.I(R539T)

How do disease control measures impact spatial predictions of schistosomiasis and hookworm? The example of predicting school-based prevalence before and after preventive chemotherapy in Ghana

BACKGROUND: Schistosomiasis and soil-transmitted helminth infections are among the neglected tropical diseases (NTDs) affecting primarily marginalized communities in low- and middle-income countries. Surveillance data for NTDs are typically sparse, and hence, geospatial predictive modeling based on remotely sensed (RS) environmental data is widely used to characterize disease transmission and treatment needs. However, as large-scale preventive chemotherapy has become a widespread practice, resulting in reduced prevalence and intensity of infection, the validity and relevance of these models should be re-assessed. METHODOLOGY: We employed two nationally representative school-based prevalence surveys of Schistosoma haematobium and hookworm infections from Ghana conducted before (2008) and after (2015) the introduction of large-scale preventive chemotherapy. We derived environmental variables from fine-resolution RS data (Landsat 8) and examined a variable distance radius (1-5 km) for aggregating these variables around point-prevalence locations in a non-parametric random forest modeling approach. We used partial dependence and individual conditional expectation plots to improve interpretability. PRINCIPAL FINDINGS: The average school-level S. haematobium prevalence decreased from 23.8% to 3.6% and that of hookworm from 8.6% to 3.1% between 2008 and 2015. However, hotspots of high-prevalence locations persisted for both diseases. The models with environmental data extracted from a buffer radius of 2-3 km around the school location where prevalence was measured had the best performance. Model performance (according to the R2 value) was already low and declined further from approximately 0.4 in 2008 to 0.1 in 2015 for S. haematobium and from approximately 0.3 to 0.2 for hookworm. According to the 2008 models, land surface temperature (LST), modified normalized difference water index (MNDWI), elevation, slope, and streams variables were associated with S. haematobium prevalence. LST, slope, and improved water coverage were associated with hookworm prevalence. Associations with the environment in 2015 could not be evaluated due to low model performance. CONCLUSIONS/SIGNIFICANCE: Our study showed that in the era of preventive chemotherapy, associations between S. haematobium and hookworm infections and the environment weakened, and thus predictive power of environmental models declined. In light of these observations, it is timely to develop new cost-effective passive surveillance methods for NTDs as an alternative to costly surveys, and to focus on persisting hotspots of infection with additional interventions to reduce reinfection. We further question the broad application of RS-based modeling for environmental diseases for which large-scale pharmaceutical interventions are in place

High-energy photoemission on Fe3O4: Small polaron physics and the Verwey transition

We have studied the electronic structure and charge ordering (Verwey) transition of magnetite (Fe3O4) by soft x-ray photoemission. Due to the enhanced probing depth and the use of different surface preparations we are able to distinguish surface and volume effects in the spectra. The pseudogap behavior of the intrinsic spectra and its temperature dependence give evidence for the existence of strongly bound small polarons consistent with both dc and optical conductivity. Together with other recent structural and theoretical results our findings support a picture in which the Verwey transition contains elements of a cooperative Jahn-Teller effect, stabilized by local Coulomb interaction

Multi-objective constrained optimization for energy applications via tree ensembles

Energy systems optimization problems are complex due to strongly non-linear system behavior and multiple competing objectives, e.g. economic gain vs. environmental impact. Moreover, a large number of input variables and different variable types, e.g. continuous and categorical, are challenges commonly present in real-world applications. In some cases, proposed optimal solutions need to obey explicit input constraints related to physical properties or safety-critical operating conditions. This paper proposes a novel data-driven strategy using tree ensembles for constrained multi-objective optimization of black-box problems with heterogeneous variable spaces for which underlying system dynamics are either too complex to model or unknown. In an extensive case study comprised of synthetic benchmarks and relevant energy applications we demonstrate the competitive performance and sampling efficiency of the proposed algorithm compared to other state-of-the-art tools, making it a useful all-in-one solution for real-world applications with limited evaluation budgets

Time-Domain Measurement of Broadband Coherent Cherenkov Radiation

We report on further analysis of coherent microwave Cherenkov impulses emitted via the Askaryan mechanism from high-energy electromagnetic showers produced at the Stanford Linear Accelerator Center (SLAC). In this report, the time-domain based analysis of the measurements made with a broadband (nominally 1-18 GHz) log periodic dipole array antenna is described. The theory of a transmit-receive antenna system based on time-dependent effective height operator is summarized and applied to fully characterize the measurement antenna system and to reconstruct the electric field induced via the Askaryan process. The observed radiation intensity and phase as functions of frequency were found to agree with expectations from 0.75-11.5 GHz within experimental errors on the normalized electric field magnitude and the relative phase; 0.039 microV/MHz/TeV and 17 deg, respectively. This is the first time this agreement has been observed over such a broad bandwidth, and the first measurement of the relative phase variation of an Askaryan pulse. The importance of validation of the Askaryan mechanism is significant since it is viewed as the most promising way to detect cosmogenic neutrino fluxes at E > 10^15 eV.Comment: 10 pages, 9 figures, accepted by Phys. Rev.

Displacement field and elastic constants in non-ideal crystals

In this work a periodic crystal with point defects is described in the framework of linear response theory for broken symmetry states using correlation functions and Zwanzig-Mori equations. The main results are microscopic expressions for the elastic constants and for the coarse-grained density, point-defect density, and displacement field, which are valid in real crystals, where vacancies and interstitials are present. The coarse-grained density field differs from the small wave vector limit of the microscopic density. In the long wavelength limit, we recover the phenomenological description of elasticity theory including the defect density.Comment: Phys Rev. B, in print (2010

Design of the ILC RTML extraction lines

The ILC [1] Damping Ring to the Main Linac beamline (RTML) contains three extraction lines (EL). Each EL can be used both for an emergency abort dumping of the beam and tune-up continual train-by-train extraction. Two of the extraction lines are located downstream of the first and second stages of the RTML bunch compressor, and must accept both compressed and uncompressed beam with energy spreads of 2.5% and 0.15%, respectively. In this paper we report on an optics design that allowed minimizing the length of the extraction lines while offsetting the beam dumps from the main line by the distance required for acceptable radiation levels in the service tunnel. The proposed extraction lines can accommodate beams with different energy spreads while at the same time providing the beam size acceptable for the aluminum dump window

New in vitro interaction-parasite reduction ratio assay for early derisk in clinical development of antimalarial combinations

The development and spread of drug-resistant phenotypes substantially threaten malaria control efforts. Combination therapies have the potential to minimize the risk of resistance development but require intensive preclinical studies to determine optimal combination and dosing regimens. To support the selection of new combinations, we developed a novel in vitro-in silico combination approach to help identify the pharmacodynamic interactions of the two antimalarial drugs in a combination which can be plugged into a pharmacokinetic/pharmacodynamic model built with human monotherapy parasitological data to predict the parasitological endpoints of the combination. This makes it possible to optimally select drug combinations and doses for the clinical development of antimalarials. With this assay, we successfully predicted the endpoints of two phase 2 clinical trials in patients with the artefenomel-piperaquine and artefenomel-ferroquine drug combinations. In addition, the predictive performance of our novel in vitro model was equivalent to that of the humanized mouse model outcome. Last, our more informative in vitro combination assay provided additional insights into the pharmacodynamic drug interactions compared to the in vivo systems, e.g., a concentration-dependent change in the maximum killing effect (Emax) and the concentration producing 50% of the killing maximum effect (EC50) of piperaquine or artefenomel or a directional reduction of the EC50 of ferroquine by artefenomel and a directional reduction of Emax of ferroquine by artefenomel. Overall, this novel in vitro-in silico-based technology will significantly improve and streamline the economic development of new drug combinations for malaria and potentially also in other therapeutic areas