5,987 research outputs found
Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers
Financial support for this project was provided by Cancer Research UK (Grant No. C21383/A6950)The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.Publisher PDFPeer reviewe
Expression profiling of snoRNAs in normal hematopoiesis and AML
Key Points
A subset of snoRNAs is expressed in a developmental- and lineage-specific manner during human hematopoiesis. Neither host gene expression nor alternative splicing accounted for the observed differential expression of snoRNAs in a subset of AML.</jats:p
TPL-2 restricts Ccl24-dependent immunity to Heligmosomoides polygyrus
Funding: This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001220), the UK Medical Research Council (FC001220), and the Wellcome Trust (FC001200). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We are indebted to The Francis Crick Institute Flow Cytometry facility, and in particular Bhavik Patel, Graham Preece, Wayne Turnbull and Phil Hobson. We would also like to thank The Francis Crick Institute Procedural Service Section for production of GA lines and Biological Services, especially Trisha Norton, Keith Williams and Adebambo Adekoya for animal husbandry and technical support; to Riccardo Guidi for constructive discussions and technical assistance. We would like to thank Gitta Stockinger and AhR Immunity Laboratory for providing technical support and reagents throughout this study. We also thank Richard Rance and the Wellcome Trust Sanger Instituteâs 454 pyrosequencing team for generating 16S rRNA gene data.Peer reviewedPublisher PD
The reaction 2H(p,pp)n in three kinematical configurations at E_p = 16 MeV
We measured the cross sections of the H(p,pp)n breakup reaction at
E=16 MeV in three kinematical configurations: the np final-state
interaction (FSI), the co-planar star (CST), and an intermediate-star (IST)
geometry. The cross sections are compared with theoretical predictions based on
the CD Bonn potential alone and combined with the updated 2-exchange
Tucson-Melbourne three-nucleon force (TM99'), calculated without inclusion of
the Coulomb interaction. The resulting excellent agreement between data and
pure CD Bonn predictions in the FSI testifies to the smallness of three-nucleon
force (3NF) effects as well as the insignificance of the Coulomb force for this
particular configuration and energy. The CST also agrees well whereas the IST
results show small deviations between measurements and theory seen before in
the pd breakup space-star geometries which point to possible Coulomb effects.
An additional comparison with EFT predictions (without 3NF) up to order NLO
shows excellent agreement in the FSI case and a rather similar agreement as for
CD Bonn in the CST and IST situations.Comment: 20 pages, 11 figure
Generalized Morse Potential: Symmetry and Satellite Potentials
We study in detail the bound state spectrum of the generalized Morse
potential~(GMP), which was proposed by Deng and Fan as a potential function for
diatomic molecules. By connecting the corresponding Schr\"odinger equation with
the Laplace equation on the hyperboloid and the Schr\"odinger equation for the
P\"oschl-Teller potential, we explain the exact solvability of the problem by
an symmetry algebra, and obtain an explicit realization of the latter
as . We prove that some of the generators
connect among themselves wave functions belonging to different GMP's (called
satellite potentials). The conserved quantity is some combination of the
potential parameters instead of the level energy, as for potential algebras.
Hence, belongs to a new class of symmetry algebras. We also stress
the usefulness of our algebraic results for simplifying the calculation of
Frank-Condon factors for electromagnetic transitions between rovibrational
levels based on different electronic states.Comment: 23 pages, LaTeX, 2 figures (on request). one LaTeX problem settle
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Insulin adsorption to catheter materials used for intensive insulin therapy in critically ill patients: Polyethylene versus polyurethane - possible cause of variation in glucose control?
Introduction: Restoring and maintaining normoglycemia by intensified insulin therapy in critically ill patients is a matter of ongoing debate since the risk of hypoglycemia may outweigh positive effects on morbidity and mortality. In this context, adsorption of insulin to different catheter materials may contribute to instability of glucose control. We studied the adsorption of insulin to different tubing materials in vitro and the effects on glycemic control in vivo. Materials and Methods: In vitro experiments: A syringe pump was filled with 50 IU insulin diluted to 50 ml saline. A flow of 2 ml/h was perfused through polyethylene (PET) or polyurethane (PUR) tubing. Insulin concentrations were measured at the end of the tube for 24 hours using Bradford's protein assay. In vivo study: In a randomized double-blinded cross-over design, 10 intensive care patients received insulin via PET and PUR tubes for 24 hours each, targeting blood glucose levels of 80-150 mg/dl. We measured blood glucose levels, the insulin dose required to maintain target levels, and serum insulin and C-peptide levels. Results: In vitro experiments: After the start of the insulin infusion, only 20% (median, IQR 20-27) (PET) and 22% (IQR 16-27) (PUR) of the prepared insulin concentration were measured at the end of the 2 meter tubing. Using PET, after one hour infusion the concentration increased to 34% (IQR 29-36) and did not increase significantly during the next 24 hours (39% (IQR 39-40)). Using PUR, higher concentrations were detected than for PET at every measurement from 1 hour (82% (IQR 70-86)) to 24 hours (79% (IQR 64-87)). In vivo study: Glycemic control was effective and not different between groups. Significantly higher volumes of insulin solution had to be infused with PET compared to PUR (median PET 70.0 (IQR 56-82) ml vs. PUR 42 (IQR 31-63) ml; p=0.0015). Serum insulin concentrations did not decrease significantly one hour after changing to PET or PUR tubing. Conclusion: Polyurethane tubing systems allow application of insulin with significantly lower adsorption rates than polyethylene tubing systems. As a consequence, less insulin solution has to be infused to patients for effective blood glucose control. Tubing material of the insulin infusion may be crucial for safe and effective glycemic control in critically ill patients
A general approach for detecting expressed mutations in AML cells using single cell RNA-sequencing
Connection Between Type A and E Factorizations and Construction of Satellite Algebras
Recently, we introduced a new class of symmetry algebras, called satellite
algebras, which connect with one another wavefunctions belonging to different
potentials of a given family, and corresponding to different energy
eigenvalues. Here the role of the factorization method in the construction of
such algebras is investigated. A general procedure for determining an so(2,2)
or so(2,1) satellite algebra for all the Hamiltonians that admit a type E
factorization is proposed. Such a procedure is based on the known relationship
between type A and E factorizations, combined with an algebraization similar to
that used in the construction of potential algebras. It is illustrated with the
examples of the generalized Morse potential, the Rosen-Morse potential, the
Kepler problem in a space of constant negative curvature, and, in each case,
the conserved quantity is identified. It should be stressed that the method
proposed is fairly general since the other factorization types may be
considered as limiting cases of type A or E factorizations.Comment: 20 pages, LaTeX, no figure, to be published in J. Phys.
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