324 research outputs found
Defining the value framework for prostate brachytherapy using patient-centered outcome metrics and time-driven activity-based costing
Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1
The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development
Simulation and background characterisation of the SABRE South experiment
SABRE (Sodium iodide with Active Background REjection) is a direct detection
dark matter experiment based on arrays of radio-pure NaI(Tl) crystals. The
experiment aims at achieving an ultra-low background rate and its primary goal
is to confirm or refute the results from the DAMA/LIBRA experiment. The SABRE
Proof-of-Principle phase was carried out in 2020-2021 at the Gran Sasso
National Laboratory (LNGS), in Italy. The next phase consists of two full-scale
experiments: SABRE South at the Stawell Underground Physics Laboratory, in
Australia, and SABRE North at LNGS. This paper focuses on SABRE South and
presents a detailed simulation of the detector, which is used to characterise
the background for dark matter searches including DAMA/LIBRA-like modulation.
We estimate an overall background of 0.72 cpd/kg/keV in the energy range
16 keV primarily due to radioactive contamination in the crystals.
Given this level of background and considering that the SABRE South has a
target mass of 50 kg, we expect to exclude (confirm) DAMA/LIBRA modulation at
within 2.5 years of data taking
Mediator Subunit 12 Is Required for Neutrophil Development in Zebrafish
Hematopoiesis requires the spatiotemporal organization of regulatory factors to successfully orchestrate diverse lineage specificity from stem and progenitor cells. Med12 is a regulatory component of the large Mediator complex that enables contact between the general RNA polymerase II transcriptional machinery and enhancer bound regulatory factors. We have identified a new zebrafish med12 allele, syr, with a single missense mutation causing a valine to aspartic acid change at position 1046. Syr shows defects in hematopoiesis, which predominantly affect the myeloid lineage. Syr has identified a hematopoietic cell-specific requirement for Med12, suggesting a new role for this transcriptional regulator
Subsurface interactions of actinide species and microorganisms: Implications for the bioremediation of actinide-organic mixtures
Nonlinear single-electron tunneling through individually coated colloid particles at room temperature
Determination of selenium in biological materials by stable isotope dilution gas chromatography-mass spectrometry
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