31 research outputs found
The Effect of Nitrogen Fixation and Plant Species on Ammonium and Amino Acids Soil Contents
Grass and legume intercropping systems, particularly ryegrass-clover mixed cultures, increase grasslands productivity, due to the clover nitrogen (N) fixation and to the transfer of part it to the companion grass. The objective of this experiment was to determine if N fixation and plant species could modify ammonium and amino acids soil contents
Effect of trace elements on the interface reactions between two lead-free solders and copper or nickel substrates
Traditional Sn-Pb solder alloys are being replaced, because of environmental and health concerns
about lead toxicity. Among some alternative alloy systems, the Sn-Zn and Sn-Cu base alloy systems
have been studied and reveal promising properties. The reliability of a solder joint is affected by the
solder/substrate interaction and the nature of the layers formed at the interface.
The solder/substrate reactions, for Sn-Zn and Sn-Cu base solder alloys, were evaluated in what
concerns the morphology and chemical composition of the interface layers. The effect of the addition
of P, at low levels, on the chemical composition of the layers present at the interface was studied. The
phases formed at the interface between the Cu or Ni substrate and a molten lead-free solder at
250Âș C, were studied for different stage times and alloy compositions. The melting temperatures, of
the studied alloys, were determined by Differential Scanning Calorimetry (DSC).
Identification of equilibrium phases formed at the interface layer, and the evaluation of their
chemical composition were performed by Scanning Electron Microscopy (SEM/EDS). Different
interface characteristics were obtained, namely for the alloys containing Zn. The obtained IML layer
thickness was compared, for both types of alloy systems.FCT - Fundação para a CiĂȘncia e Tecnologi
Logarithmic Corrections for Spin Glasses, Percolation and Lee-Yang Singularities in Six Dimensions
We study analytically the logarithmic corrections to the critical exponents
of the critical behavior of correlation length, susceptibility and specific
heat for the temperature and the finite-size scaling behavior, for a generic
theory at its upper critical dimension (six). We have also computed
the leading correction to scaling as a function of the lattice size. We
distinguish the obtained formulas to the following special cases: percolation,
Lee-Yang (LY) singularities and -component spin glasses. We have compared
our results for the Ising spin glass case with numerical simulations finding a
very good agreement. Finally, and using the results obtained for the Lee-Yang
singularities in six dimensions, we have computed the logarithmic corrections
to the singular part of the free energy for lattice animals in eight
dimensions.Comment: 18 pages. We have extended the computation to lattice animals in
eight dimensions. To be published in Journal of Physics
The novel anti-cancer fluoropyrimidine NUC-3373 is a potent inhibitor of thymidylate synthase and an effective DNA-damaging agent
Funding: GMZ and CMC are funded by research grant from NuCana plc. PT is funded by IBioIC, CMC is funded by the Wellcome trust (217078/Z/19/Z).Introduction Fluoropyrimidines, principally 5-fluorouracil (5-FU), remain a key component of chemotherapy regimens for multiple cancer types, in particular colorectal and other gastrointestinal malignancies. To overcome key limitations and pharmacologic challenges that hinder the clinical utility of 5-FU, NUC-3373, a phosphoramidate transformation of 5-fluorodeoxyuridine, was designed to improve the efficacy and safety profile as well as the administration challenges associated with 5-FU. Methods Human colorectal cancer cell lines HCT116 and SW480 were treated with sub-IC50 doses of NUC-3373 or 5-FU. Intracellular activation was measured by LCâMS. Western blot was performed to determine binding of the active anti-cancer metabolite FdUMP to thymidylate synthase (TS) and DNA damage. Results We demonstrated that NUC-3373 generates more FdUMP than 5-FU, resulting in a more potent inhibition of TS, DNA misincorporation and subsequent cell cycle arrest and DNA damage in vitro. Unlike 5-FU, the thymineless death induced by NUC-3373 was rescued by the concurrent addition of exogenous thymidine. 5-FU cytotoxicity, however, was only reversed by supplementation with uridine, a treatment used to reduce 5-FU-induced toxicities in the clinic. This is in line with our findings that 5-FU generates FUTP which is incorporated into RNA, a mechanism known to underlie the myelosuppression and gastrointestinal inflammation associated with 5-FU. Conclusion Taken together, these results highlight key differences between NUC-3373 and 5-FU that are driven by the anti-cancer metabolites generated. NUC-3373 is a potent inhibitor of TS that also causes DNA-directed damage. These data support the preliminary clinical evidence that suggest NUC-3373 has a favorable safety profile in patients.Publisher PDFPeer reviewe
Genome-scale CRISPR/Cas9 screen determines factors modulating sensitivity to ProTide NUC-1031
A.S. is the recipient of a Medical Research Scotland PhD Studentship awarded to P.A.R. Edinburgh Genomics is partly supported through core grants from Natural Environment Research Council (R8/H10/56), Medical Research Council (MR/K001744/1) and Biotechnological and Biological Research Council (BB/J004243/1). Publication of this article was funded in part by the University of St Andrews Open Access Publishing Fund.Gemcitabine is a fluoropyrimidine analogue that is used as a mainstay of chemotherapy treatment for pancreatic and ovarian cancers, amongst others. Despite its widespread use, gemcitabine achieves responses in less than 10% of patients with metastatic pancreatic cancer and has a very limited impact on overall survival due to intrinsic and acquired resistance. NUC-1031 (Acelarin), a phosphoramidate transformation of gemcitabine, was the first anti-cancer ProTide to enter the clinic. We find it displays important in vitro cytotoxicity differences to gemcitabine, and a genome-wide CRISPR/Cas9 genetic screening approach identified only the pyrimidine metabolism pathway as modifying cancer cell sensitivity to NUC-1031. Low deoxycytidine kinase expression in tumour biopsies from patients treated with gemcitabine, assessed by immunostaining and image analysis, correlates with a poor prognosis, but there is no such correlation in tumour biopsies from a Phase I cohort treated with NUC-1031.Publisher PDFPeer reviewe
Effect of trace elements on the interface reactions between two lead-free solders and copper or nickel substrates
Traditional Sn-Pb solder alloys are being replaced, because of environmental and health concerns about lead toxicity. Among some alternative alloy systems, the Sn-Zn and Sn-Cu base alloy systems have been studied and reveal promising properties. The reliability of a solder joint is affected by the solder/substrate interaction and the nature of the layers formed at the interface. The solder/substrate reactions, for Sn-Zn and Sn-Cu base solder alloys, were evaluated in what concerns the morphology and chemical composition of the interface layers. The effect of the addition of P, at low levels, on the chemical composition of the layers present at the interface was studied. The phases formed at the interface between the Cu or Ni substrate and a molten lead-free solder at 250ÂșC, were studied for different stage times and alloy compositions. The melting temperatures, of the studied alloys, were determined by Differential Scanning Calorimetry (DSC). Identification of equilibrium phases formed at the interface layer, and the evaluation of their chemical composition were performed by Scanning Electron Microscopy (SEM/EDS). Different interface characteristics were obtained, namely for the alloys containing Zn. The obtained IML layer thickness was compared, for both types of alloy systems
Structural Characterization by Tandem Mass Spectrometry of the Posttranslational Polyglycylation of Tubulin
Paramecium tetraurelia: The Renaissance of an Early Unicellular Model
International audienc
Paramecium tetraurelia: The Renaissance of an Early Unicellular Model
International audienc