Synthesis, biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidal–antiplasmodial activity.

YesDual submicromolar trypanocidal–antiplasmodial compounds have been identified by screening and chemical synthesis of 4-aminoquinoline-based heterodimeric compounds of three different structural classes. In Trypanosoma brucei, inhibition of the enzyme trypanothione reductase seems to be involved in the potent trypanocidal activity of these heterodimers, although it is probably not the main biological target. Regarding antiplasmodial activity, the heterodimers seem to share the mode of action of the antimalarial drug chloroquine, which involves inhibition of the haem detoxification process. Interestingly, all of these heterodimers display good brain permeabilities, thereby being potentially useful for late stage human African trypanosomiasis. Future optimization of these compounds should focus mainly on decreasing cytotoxicity and acetylcholinesterase inhibitory activity

Proton Elastic and Inelastic Scattering at Intermediate Energies from Isotopes of Oxygen and 9-Be as Part of a Unified Study of These Nuclei

This work was supported by National Science Foundation Grants PHY 76-84033A01, PHY 78-22774, and Indiana Universit

Proton Elastic and Inelastic Scattering at Intermediate Energies from Isotopes of Oxygen and 9-Be as Part of a Unified Study of these Nuclei

This work was supported by the National Science Foundation Grants NSF PHY 78-22774 A03, NSF PHY 81-14339, and by Indiana Universit

Proton Elastic and Inelastic Scattering at Intermediate Energies from Isotopes of Oxygen and 9-Be as Part of a Unified Study of These Nuclei

This work was supported by the National Science Foundation Grant NSF PHY 78-22774 A02 & A03 and by Indiana Universit

Meson exchange currents in electromagnetic one-nucleon emission

The role of meson exchange currents (MEC) in electron- and photon-induced one-nucleon emission processes is studied in a nonrelativistic model including correlations and final state interactions. The nuclear current is the sum of a one-body and of a two-body part. The two-body current includes pion seagull, pion-in-flight and the isobar current contributions. Numerical results are presented for the exclusive 16O(e,e'p)15N and 16O(\gamma,p)15N reactions. MEC effects are in general rather small in (e,e'p), while in (\gamma,p) they are always large and important to obtain a consistent description of (e,e'p) and (\gamma,p) data, with the same spectroscopic factors. The calculated (\gamma,p) cross sections are sensitive to short-range correlations at high values of the recoil momentum, where MEC effects are larger and overwhelm the contribution of correlations.Comment: 9 pages, 6 figure

Proton Elastic and Inelastic Scattering at Intermediate Energies from Isotopes of Oxygen and 9-Be as Part of a Unified Study of These Nuclei

Supported by the National Science Foundation and Indiana Universit

Quark Imaging in the Proton Via Quantum Phase-Space Distributions

We develop the concept of quantum phase-space (Wigner) distributions for quarks and gluons in the proton. To appreciate their physical content, we analyze the contraints from special relativity on the interpretation of elastic form factors, and examine the physics of the Feynman parton distributions in the proton's rest frame. We relate the quark Wigner functions to the transverse-momentum dependent parton distributions and generalized parton distributions, emphasizing the physical role of the skewness parameter. We show that the Wigner functions allow to visualize quantum quarks and gluons using the language of the classical phase space. We present two examples of the quark Wigner distributions and point out some model-independent features.Comment: 20 pages with 3 fiture

Relativistic corrections in (gamma,N) knockout reactions

We develop a fully relativistic DWIA model for photonuclear reactions using the relativistic mean field theory for the bound state and the Pauli reduction of the scattering state which is calculated from a relativistic optical potential. Results for the 12C(gamma,p) and 16O(gamma,p) differential cross sections and photon asymmetries are displayed in a photon energy range between 60 and 257 MeV, and compared with nonrelativistic DWIA calculations. The effects of the spinor distortion and of the effective momentum approximation for the scattering state are discussed. The sensitivity of the model to different prescriptions for the one-body current operator is investigated. The off-shell ambiguities are large in (gamma,p) calculations, and even larger in (gamma,n) knockout.Comment: LaTeX2e, 18 pages, and 6 figure

Spallation reactions. A successful interplay between modeling and applications

The spallation reactions are a type of nuclear reaction which occur in space by interaction of the cosmic rays with interstellar bodies. The first spallation reactions induced with an accelerator took place in 1947 at the Berkeley cyclotron (University of California) with 200 MeV deuterons and 400 MeV alpha beams. They highlighted the multiple emission of neutrons and charged particles and the production of a large number of residual nuclei far different from the target nuclei. The same year R. Serber describes the reaction in two steps: a first and fast one with high-energy particle emission leading to an excited remnant nucleus, and a second one, much slower, the de-excitation of the remnant. In 2010 IAEA organized a worskhop to present the results of the most widely used spallation codes within a benchmark of spallation models. If one of the goals was to understand the deficiencies, if any, in each code, one remarkable outcome points out the overall high-quality level of some models and so the great improvements achieved since Serber. Particle transport codes can then rely on such spallation models to treat the reactions between a light particle and an atomic nucleus with energies spanning from few tens of MeV up to some GeV. An overview of the spallation reactions modeling is presented in order to point out the incomparable contribution of models based on basic physics to numerous applications where such reactions occur. Validations or benchmarks, which are necessary steps in the improvement process, are also addressed, as well as the potential future domains of development. Spallation reactions modeling is a representative case of continuous studies aiming at understanding a reaction mechanism and which end up in a powerful tool.Comment: 59 pages, 54 figures, Revie

ARMED to ESCAPE COVID-19 : the impact of COVID-19 on a mixed methods feasibility study of a weight management, education and physical function programme for patients with knee osteoarthritis at the primary/secondary care interface

OBJECTIVES: This study was designed to test the feasibility of running a trial to compare the effectiveness of a combined weight management and physical function programme for patients with knee osteoarthritis ARMED (Arthritis Rehabilitation through the Management of Exercise and Diet) with usual care ESCAPE pain (Enabling Self-management and Coping with Arthritic Pain using Exercise). The COVID-19 pandemic interruption allowed additional measurement of the qualitative ‘lived in’ experiences of this patient group during the pandemic and also their appetite for virtual health. PARTICIPANTS: Thirty-two patients with knee osteoarthritis were recruited from a combined primary/secondary care waiting list and were allocated to either a six-week intervention group (ARMED) or to the six-week usual care ESCAPE pain group (Enabling Self-management and Coping with Arthritic Pain using Exercise) group. RESULTS: The intervention programme was interrupted after three weeks by COVID-19. Fifteen patients were reassessed after the first stage. The average attendance was 92% with 6 patients attending all sessions, 5 attending 5/6, 1 attending 4/6 and 2 attending 3/6. One subject dropped out and 15/16 patients completed all outcome measurements. All patients completed the KOOS knee score and the Short Warwick-Edinburgh Mental Well Being Scale to evaluate anxiety and depression. There was a statistically significant improvement in pain, activities of daily living, quality of life and mental health and well-being scores from time one to time 2. The mean weight, BMI and waist measurements were reduced also from time one to time 2, but these failed to reach significance. The semi-structured interviews provided rich information on enablers and barriers to coping in lockdown, benefits of the ARMED programme to increasing physical activity and weight management and enablers and barriers to redesigning the programme for online delivery. CONCLUSIONS: Evaluation of preliminary data from this feasibility study supports the three-week intervention combining education, exercise and weight management in this patient group even during a pandemic. Based on the results of the qualitative interviews, we have now redesigned our programme to present it virtually. We hope to present the results of our virtual feasibility study later in 2021