Synthesis of mono and Bis[60]fullerene-based dicationic peptoids

Increasing numbers of biological applications of fullerenyl amino acids and their derivatives encouraged us to synthesise [60]fullerenyldihydropyrrole peptides, prepared from the coupling of mono- and bis[60]fullerenyldihydropyrrolecarboxylic acids 4, 5 and 41 with presynthesised peptides 13, 16, 24, 28, 29 and 46. The resulting hydrophobic scaffolded di- and tetra-cationic derivatives were tested against Staphylococcus aureus NCTC 6571 and Escherichia coli NCTC 10418. The synthesis, characterisation and biological results are discussed in this paper

Binaphthyl-1,2,3-triazole peptidomimetics with activity against Clostridium difficile and other pathogenic bacteria

Clostridium difficile (C. difficile) is a problematic Gram positive bacterial pathogen causing moderate to severe gastrointestinal infections. Based on a lead binaphthyl-tripeptide dicationic antimicrobial, novel mono-, di- and tri-peptidomimetic analogues targeting C. difficile were designed and synthesized incorporating one, two or three d-configured cationic amino acid residues, with a common 1,2,3-triazole ester isostere at the C-terminus. Copper- and ruthenium-click chemistry facilitated the generation of a 46 compound library for in vitro bioactivity assays, with structure-activity trends over the largest compound subset revealing a clear advantage to triazole-substitution with a linear or branched hydrophobic group. The most active compounds were dicationic-dipeptides where the triazole was substituted with a 4- or 5-cyclohexylmethyl or 4,5-diphenyl moiety, providing MICs of 4 μg mL-1 against three human isolates of C. difficile. Further biological screening revealed significant antimicrobial activity for several compounds against other common bacterial pathogens, both Gram positive and negative, including S. aureus (MICs ≥2 μg mL-1), S. pneumoniae (MICs ≥1 μg mL-1), E. coli (MICs ≥4 μg mL-1), A. baumannii (MICs ≥4 μg mL-1) and vancomycin-resistant E. faecalis (MICs ≥4 μg mL-1)

Parathyroid scintigraphy findings in chronic kidney disease patients with recurrent hyperparathyroidism

Background Parathyroidectomy (PTX), either subtotal or total with forearm autografting, is a well-established treatment for refractory renal hyperparathyroidism (RHPT). However, 20–30% of patients develop persistent or recurrent disease. Obtaining accurate localization before reoperation is difficult. Patients and methods The study group comprised 21 consecutive adult patients (18 undergoing haemodialysis and 3 with a renal graft) imaged using 99mTc-sestamibi/123I subtraction scintigraphy. Of the 21 patients, 12 had undergone one previous PTX and the other 9 between two and four parathyroid operations. All patients had symptoms and signs of severe RHPT. The mean serum PTH level was 1,142 pg/ml. 99mTc-Sestamibi and 123I images were recorded simultaneously. Imaging views comprised a planar view of the neck and mediastinum, followed by a magnified pinhole view over the thyroid bed area. If parathyroid ectopy was detected, SPECT or SPECT-CT was performed. The forearm was imaged in case of autograft. Results Parathyroid scintigraphy was negative in one patient and positive in the other 20 (sensitivity 95.2%). One patient had uptake corresponding to two unresected parathyroid glands. Recurrence at the site of the partially resected gland or autograft was seen in 11 patients. However, six of them had a second 99mTc-sestamibi focus corresponding to a supernumerary parathyroid gland. Seven other patients had a supernumerary parathyroid gland as the sole cause of relapse. Three of the supernumerary glands showed major ectopy (intrathyroidal, low mediastinal, undescended within the vagus nerve). One patient had parathyromatosis with multiple parathyroid nodules scattered over the left side of the neck. Reoperation was possible in 13 patients, with no false-positive findings. Conclusion Many patients referred with the hypothesis of hyperplasia of a subtotally resected parathyroid gland or autograft were found to harbour a supernumerary parathyroid gland missed at the initial surgery

Transition to an Insulating Phase Induced by Attractive Interactions in the Disordered Three-Dimensional Hubbard Model

We study numerically the interplay of disorder and attractive interactions for spin-1/2 fermions in the three-dimensional Hubbard model. The results obtained by projector quantum Monte Carlo simulations show that at moderate disorder, increasing the attractive interaction leads to a transition from delocalized superconducting states to the insulating phase of localized pairs. This transition takes place well within the metallic phase of the single-particle Anderson model.Comment: revtex, 4 pages, 3 figure

A Mathematical Model of Liver Cell Aggregation In Vitro

The behavior of mammalian cells within three-dimensional structures is an area of intense biological research and underpins the efforts of tissue engineers to regenerate human tissues for clinical applications. In the particular case of hepatocytes (liver cells), the formation of spheroidal multicellular aggregates has been shown to improve cell viability and functionality compared to traditional monolayer culture techniques. We propose a simple mathematical model for the early stages of this aggregation process, when cell clusters form on the surface of the extracellular matrix (ECM) layer on which they are seeded. We focus on interactions between the cells and the viscoelastic ECM substrate. Governing equations for the cells, culture medium, and ECM are derived using the principles of mass and momentum balance. The model is then reduced to a system of four partial differential equations, which are investigated analytically and numerically. The model predicts that provided cells are seeded at a suitable density, aggregates with clearly defined boundaries and a spatially uniform cell density on the interior will form. While the mechanical properties of the ECM do not appear to have a significant effect, strong cell-ECM interactions can inhibit, or possibly prevent, the formation of aggregates. The paper concludes with a discussion of our key findings and suggestions for future work

Antiferromagnetic Domains and Superconductivity in UPt3

We explore the response of an unconventional superconductor to spatially inhomogeneous antiferromagnetism (SIAFM). Symmetry allows the superconducting order parameter in the E-representation models for UPt3 to couple directly to the AFM order parameter. The Ginzburg-Landau equations for coupled superconductivity and SIAFM are solved numerically for two possible SIAFM configurations: (I) abutting antiferromagnetic domains of uniform size, and (II) quenched random disorder of `nanodomains' in a uniform AFM background. We discuss the contributions to the free energy, specific heat, and order parameter for these models. Neither model provides a satisfactory account of experiment, but results from the two models differ significantly. Our results demonstrate that the response of an E_{2u} superconductor to SIAFM is strongly dependent on the spatial dependence of AFM order; no conclusion can be drawn regarding the compatibility of E_{2u} superconductivity with UPt3 that is independent of assumptions on the spatial dependence of AFMComment: 12 pages, 13 figures, to appear in Phys. Rev.

DMSP synthesis and exudation in phytoplankton:a modeling approach

In the marine environment, phytoplankton are the fundamental producers of dimethylsulfoniopropionate (DMSP), the precursor of the climatically active gas dimethylsulfide (DMS). DMSP is released by exudation, cell autolysis, and zooplankton grazing during phytoplankton blooms. In this study, we developed a model of phytoplankton DMSP and DMS production allowing quantification of the exudation rates of these compounds during different growth phases. The model was tested on published data from axenic cultures of Prorocentrum minimum and Phaeocystis sp.; DMSP exudation rates vary considerably between the 2 species. Model results show that P. minimum exudes around 1% d(-1) of its DMSP quota during the latent, exponential and senescent phases. This is comparable to the average exudation rate estimated from previous laboratory experiments. However, Phaeocystis sp. exudes from 3 to 11% d(-1) of its DMSP quota. For this species, DMSP exudation rates apparently show an inverse relationship with the population growth rate. The maximum DMSP exudation rate in Phaeocystis sp. is 10 times higher than previously reported DMSP or DMS exudation rates. Our results suggest that exudation may be as important as cell autolysis in the release of DMSP during Phaeocystis sp. blooms. We conclude that exudation should be incorporated in models of DMS cycling in the marine environment. Moreover, our results for Phaeocystis sp. suggest that a low and constant exudation rate, as sometimes used in models, is not suitable for all conditions

Physics of rotation in stellar models

In these lecture notes, we present the equations presently used in stellar interior models in order to compute the effects of axial rotation. We discuss the hypotheses made. We suggest that the effects of rotation might play a key role at low metallicity.Comment: 32 pages, 7 figures, lectures, CNRS school, will be published by Springe

Come back Marshall, all is forgiven? : Complexity, evolution, mathematics and Marshallian exceptionalism

Marshall was the great synthesiser of neoclassical economics. Yet with his qualified assumption of self-interest, his emphasis on variation in economic evolution and his cautious attitude to the use of mathematics, Marshall differs fundamentally from other leading neoclassical contemporaries. Metaphors inspire more specific analogies and ontological assumptions, and Marshall used the guiding metaphor of Spencerian evolution. But unfortunately, the further development of a Marshallian evolutionary approach was undermined in part by theoretical problems within Spencer's theory. Yet some things can be salvaged from the Marshallian evolutionary vision. They may even be placed in a more viable Darwinian framework.Peer reviewedFinal Accepted Versio