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Background: A bioanalytical team dedicated to in vivo pharmacology was set up to accelerate the selection and characterization of compounds to be evaluated in animal models in oncology. Results: A DBS-based serial microsampling procedure was optimized from sample collection to extraction to obtain a generic procedure. UHPLC–high-resolution mass spectrometer configuration allowed for fast quantitative and qualitative analysis. Using an optimized lead compound, we show how bioanalysis supported in vivo pharmacology by generating blood and tumor exposure, drug monitoring and PK/PD data. Conclusion: This process provided unique opportunities for the characterization of drug properties, selection and assessment of compounds in animal models and to support and expedite proof-of-concept studies in oncology.

International audience; Variations of the lattice parameter can significantly change the properties of a material, and, in particular, its electronic behaviour. In the case of graphene, however, variations of the lattice constant with respect to graphite have been limited to less than 2.5% due to its well-established high in-plane stiffness. Here, through systematic electronic and lattice structure studies, we report regions where the lattice constant of graphene monolayers grown on copper by chemical vapour deposition increases up to ~7.5% of its relaxed value. Density functional theory calculations confirm that this expanded phase is energetically metastable and driven by the enhanced interaction between the substrate and the graphene adlayer. We also prove that this phase possesses distinctive chemical and electronic properties. The inherent phase complexity of graphene grown on copper foils revealed in this study may inspire the investigation of possible metastable phases in other seemingly simple heterostructure systems.

A problem of electromagnetic wave scattering from cylindrical posts of arbitrary cross section located in waveguide junction is presented. The method of analysis is based on the direct field matching technique. Multimode scattering matrices of every section of waveguide junction are calculated and cascading procedure is utilized to investigate the whole structure. The results are verified by comparing them with those obtained from the mode matching method analysis as well as commercial software calculations.

van der Waals heterostructures, vertical stacks of layered materials, offer new opportunities for novel quantum phenomena which are absent in their constituent components. Here we report the emergence of polaron quasiparticles at the interface of graphene/hexagonal boron nitride (h-BN) heterostructures. Using nanospot angle-resolved photoemission spectroscopy, we observe zone-corner replicas of h-BN valence band maxima, with energy spacing coincident with the highest phonon energy of the heterostructure, an indication of Fröhlich polaron formation due to forward-scattering electron-phonon coupling. Parabolic fitting of the h-BN bands yields an effective mass enhancement of ∼2.3, suggesting an intermediate coupling strength. Our theoretical simulations based on Migdal-Eliashberg theory corroborate the experimental results, allowing the extraction of microscopic physical parameters. Moreover, renormalization of graphene π-band is observed due to the hybridization with the h-BN band. Our work generalizes the polaron study from transition metal oxides to van der Waals heterostructures with higher material flexibility, highlighting interlayer coupling as an extra degree of freedom to explore emergent phenomena.

Bilayer graphene is a highly tunable material: not only can one tune the Fermi energy using standard gates, as in single-layer graphene, but the band structure can also be modified by external perturbations such as transverse electric fields or strain. We review the theoretical basics of the band structure of bilayer graphene and study the evolution of the band structure under the influence of these two external parameters. We highlight their key role concerning the ease to experimentally probe the presence of a Lifshitz transition, which consists in a change of Fermi contour topology as a function of energy close to the edges of the conduction and valence bands. Using a device geometry that allows the application of exceptionally high displacement fields, we then illustrate in detail the way to probe the topology changes experimentally using quantum Hall effect measurements in a gapped bilayer graphene system., Comment: To be published in Synthetic Metals, special issue "Advances in Graphene"

Van der Waals heterostructures of graphene and hexagonal boron nitride feature a moire superlattice for graphene's Dirac electrons. Here, we review the effects generated by this superlattice, including a specific miniband structure featuring gaps and secondary Dirac points, and a fractal spectrum of magnetic minibands known as Hofstadter's butterfly.

The band structures of bulk transition metal dichalcogenides ReS2 and ReSe2 are presented, showing the complicated nature of interband transitions inthese materials, with several close-lying band gaps. Three-dimensional plotsof constant energy surfaces in the Brillouin zone at energies near the bandextrema are used to show that the valence band maximum and conductionband minimum may not be located at special high symmetry points. We findthat both materials are indirect gap materials and that one must be careful toconsider the whole Brillouin zone volume in addressing this question.

(−)-Cryptopleurine 1 is one of the most potent anti-proliferative member of the phenanthroquinolizidine class of alkaloids. We report here the synthesis of (−)-6-O-desmethylcryptopleurine (−)-2 and (−)-6-O-desmethyl-(15R)-hydroxycryptopleurine (−)-4 in their enantiomerically enriched form through a convergent synthetic route, where the chirality is introduced by the use of commercially available (R)-methyl piperidine-2-carboxylate hydrochloride 17. Anti-proliferative activities of these compounds were evaluated on a panel of four cancer cell lines, revealing that compounds (−)-2 and (−)-4 are potent cytotoxic compared to cryptopleurine.

Using the continuum model, we investigate theoretically contribution of the low-energy electronic excitations to the Raman spectrum of superconducting monolayer graphene. We consider superconducting phases characterised by an isotropic order parameter in a single valley and find a Raman peak at a shift set by the size of the superconducting gap. The height of this peak is proportional to the square root of the gap and the third power of the Fermi level, and we estimate its quantum efficiency as $I\sim10^{-14}$., 7 pages, 2 figures

In this paper a machine learning algorithm was applied to analyze the integrated data responses of magnetic multi-sensor matrix transducer. In order to proceed the algorithm, a large database was prepared considering measurement as well as simulation results. A finite element method was utilized to conduct a numerical calculation and provide transducers response signals for the various configurations of defects. The deep artificial neural network was used for implementation of machine learning algorithm and then the model was verified.

Nearly aligned graphene on hexagonal boron nitride (G/BN) can be accurately modeled by a Dirac Hamiltonian perturbed by smoothly varying moir\'e pattern pseudospin fields. Here, we present the moir\'e-band model of G/BN for arbitrary small twist angles under a framework that combines symmetry considerations with input from ab-initio calculations. Our analysis of the band gaps at the primary and secondary Dirac points highlights the role of inversion symmetry breaking contributions of the moir\'e patterns, leading to primary Dirac point gaps when the moir\'e strains give rise to a finite average mass, and to secondary gaps when the moir\'e pseudospin components are mixed appropriately. The pseudomagnetic strain fields which can reach values of up to $\sim$40 Tesla near symmetry points in the moir\'e cell stem almost entirely from virtual hopping and dominate over the contributions arising from bond length distortions due to the moir\'e strains., Comment: 14 pages, 8 figures, 3 tables

Leitbilder 'guter Kindheit' und ungleiches Kinderleben

Leitbilder 'guter Kindheit' und ungleiches Kinderleben

We investigate theoretically the interplay between the effects of a perpendicular electric field and incommensurability at the interface on the electronic properties of a heterostructure of bilayer graphene and a semiconducting substrate with a unit cell almost three times larger than that of graphene. It is known that the former introduces an asymmetry in the distribution of the electronic wave function between the layers and opens a band gap in the electronic spectrum. The latter generates a long wavelength periodic moir\'e perturbation of graphene electrons which couples states in inequivalent graphene Brillouin zone corners and leads to the formation of minibands. We show that, depending on the details of the moir\'e perturbation, the miniband structure can be tuned from that with a single band gap at the neutrality point and overlapping minibands on the conduction/valence band side to a situation where a single narrow miniband is separated by gaps from the rest of the spectrum.

We investigate the magnetic minibands of a heterostructure consisting of bilayer graphene (BLG) and hexagonal boron nitride (hBN) by numerically diagonalizing a two-band Hamiltonian that describes electrons in BLG in the presence of a moire potential. Due to inversion-symmetry breaking characteristic for the moire potential, the valley symmetry of the spectrum is broken, but despite this, the zero-energy Landau level in BLG survives, albeit with reduced degeneracy. In addition, we derive effective models for the low-energy features in the magnetic minibands and demonstrate the appearance of secondary Dirac points in the valence band, which we confirm by numerical simulations. Then, we analyze how single-particle gaps in the fractal energy spectrum produce a sequence of incompressible states observable under a variation of carrier density and magnetic field., Comment: 8 pages, 4 figures

Olivier LaRochelle 1* , Sarah Bertoli 2* , Francois Vergez 1,3* , Jean-Emmanuel Sarry 3 , Veronique Mansat-De Mas 1,3,4 , Sophie Dobbelstein 1 , Nicole Dastugue 1 , Anne-Claire Strzelecki 1 , Cindy Cavelier 1 , Laurent Creancier 5 , Arnaud Pillon 5 , Anna Kruczynski 5 , Cecile Demur 1,3 , Audrey Sarry 2 , Francoise Huguet 2 , Anne Huynh 2 , Christian Recher 2,3,4* and Eric Delabesse 1,3,4* 1 Laboratoire d’Hematologie, CHU de Toulouse, Hopital Purpan 2 Service d’Hematologie, CHU de Toulouse, Hopital Purpan, 31059 Toulouse, France 3 INSERM UMR1037-Cancer Research Center of Toulouse, CNRS ERL 5294, Pavillon Lefebvre BP3028, CHU Purpan, 31024 Toulouse, France 4 Universite Toulouse III Paul Sabatier, Toulouse, France 5 Centre de Recherche et Developpement Pierre Fabre, 3 avenue Hubert Curien, BP 13562, 31035 Toulouse Cedex 1, France * These authors contributed equally to the work Received: November 1, 2011; Accepted: November 1, 2011; Published: November 9, 2011; Keywords: DNMT3A, acute leukemia, idarubicin, NOD/SCID, xenograft Correspondence: Eric Delabesse, email: // // Abstract Mutations in DNMT3A encoding DNA methyltransferase 3A were recently described in patients with acute myeloid leukemia. To assess their prognostic significance, we determined the mutational status of DNMT3A exon 23 in 288 patients with AML excluding acute promyelocytic leukemia, aged from 18 to 65 years and treated in Toulouse University Hospital. A mutation was detected in 39 patients (13.5%). All DNMT3A exon 23+ patients had intermediate-risk cytogenetics. Mutations significantly correlated with a higher WBC count (p

We review the effect of uniaxial strain on the low-energy electronic dispersion and Landau level structure of bilayer graphene. Based on the tight-binding approach, we derive a strain-induced term in the low-energy Hamiltonian and show how strain affects the low-energy electronic band structure. Depending on the magnitude and direction of applied strain, we identify three regimes of qualitatively different electronic dispersions. We also show that in a weak magnetic field, sufficient strain results in the filling factor ff=+-4 being the most stable in the quantum Hall effect measurement, instead of ff=+-8 in unperturbed bilayer at a weak magnetic field. To mention, in one of the strain regimes, the activation gap at ff=+-4 is, down to very low fields, weakly dependent on the strength of the magnetic field., Comment: 14 single-column pages, 5 figures, more details on material presented in arXiv:1104.5029

F14512 exploiting the polyamine transport system (PTS) for tumour cell delivery has been described as a potent antitumour agent. The optimal use of this compound will require a probe to identify tumour cells expressing a highly active PTS that might be more sensitive to the treatment. The aim of this study was to design and characterize a scintigraphic probe to evaluate its uptake in cancer cells expressing the PTS.Three polyamines coupled to a hydrazinonicotinamide (HYNIC) moiety were synthesized and labelled with 99mTc. Their radiochemical purity was determined by HPLC. The plasma stability of the 99mTc-HYNIC-spermine probe and its capacity to accumulate into PTS-active cells were also evaluated. In vitro internalization was tested using murine melanoma B16/F10 cells and human lung carcinoma A549 cells. Biodistribution was determined in healthy mice and tumour uptake was studied in B16/F10 tumour-bearing mice. A HL-60-Luc human leukaemia model was used to confront single photon emission computed tomography (SPECT) images obtained with the 99mTc-labelled probe with those obtained by bioluminescence.The 99mTc-HYNIC-spermine probe was selected for its capacity to accumulate into PTS-active cells and its stability in plasma. In vitro studies demonstrated that the probe was internalized in the cells via the PTS. In vivo measurements indicated a tumour to muscle scintigraphic ratio of 7.9±2.8. The combined bioluminescence and scintigraphic analyses with the leukaemia model demonstrated that the spermine conjugate accumulates into the tumour cells.The 99mTc-HYNIC-spermine scintigraphic probe is potentially useful to characterize the PTS activity of tumours. Additional work is needed to determine if this novel conjugate may be useful to analyse the PTS status of patients with solid tumours.

Continuous microwave saturation of EPR spectra of melanin complexes at different temperatures Paramagnetic centers in DOPA-melanin and complexes of DOPA-melanin with netilmicin and Cu(II) were studied by the use of an X-band (9.3 GHz) electron paramagnetic resonance (EPR) spectroscopy. Measurements of continuous microwave saturation of EPR spectra at temperatures: 125 K, 175 K, 225 K, 275 K, were performed. Homogeneous broadening of all the examined EPR spectra was observed. EPR spectra of DOPA-melanin-Cu(II) complexes saturated at higher microwave powers than the others tested melanin samples. Fast spin-lattice relaxation exists in DOPA-melanin-Cu(II) complexes. Slow spin-lattice relaxation processes exist in melanin's paramagnetic centers of DOPA-melanin and its complexes with netilmicin, and its complexes with both netilimicin and Cu(II). EPR spectra of all the tested samples saturated at higher microwave powers with increasing of the measuring temperature. Faster spin-lattice relaxation processes occurs in DOPA-melanin and its complexes with netilmicin and Cu(II) at higher temperature.

The authors unanimously wish to retract this Article due to their concerns about the interpretation of the low-energy electron microscopy (LEEM) and diffraction (LEED) patterns reported in the manuscript. In this study, the authors used spatial and angle-resolved photoemission spectroscopy (ARPES) to characterize graphene monolayers grown on copper foils, and observed regions of graphene adlayers with enhanced graphene/Cu interaction, higher Dirac cone doping level, moire mini Dirac cones and large lattice expansion. All these properties have been clearly verified and reproduced by photoemission spectroscopy as well as explained by density functional theory. LEEM and LEED characterization were also carried out to confirm the existence of a moire superlattice and lattice expansion, and the results were included in the main manuscript and Supplementary Information. On further analysis of the LEEM/LEED data, it seems that while the existence of a moire superlattice can be corroborated, the conclusion of graphene lattice expansion (7%) based on spatially resolved ARPES determinations cannot be confirmed by the LEEM/LEED measurements. The authors realized that these measurements were collected from statistically non-representative areas of the sample. Moreover, the fact that the raw microLEED images bear an asymmetry factor of as much as 5% due to the instrumental aberration makes it impossible to estimate any compression or expansion of the same order. Consequently, their conclusion on the graphene lattice expansion can only be supported by the photoemission data. In view that more complete and reliable structural determinations should be conducted, all authors wish to retract this Article.

Polo like kinase-1 is a key effector of cell division and its overexpression in several cancers is often linked with negative prognostic. We recently described that Plk1 is overexpressed in acute myeloid leukemia, and that its inhibition selectively reduces the proliferation of leukemic cells. Here, we report that Plk1 inhibition or depletion using pharmacological and siRNA approaches decreased the phosphorylation of two mTOR substrates in AML cells. In HCT116 cells, inducible expression of a constitutively active form of Plk1 leads to activation of mTOR, as shown by increased phosphorylation of its 4E-BP1 and RPS6 down-stream targets. In addition, cells overexpressing the active form of Plk1 were characterized by abnormal growth that could be reversed by rapamycin, a specific inhibitor of the TORC1 complex. Altogether these data suggest the existence of a molecular and functional link between the Plk1 mitotic kinase and the mTOR pathway. Given the different established functions of Plk1 and mTOR during the cell cycle, we will discuss the possible meaning of this functional relationship.

We present a self-consistent calculation of the interlayer asymmetry in bilayer graphene caused by an applied electric field in magnetic fields. We show how this asymmetry influences the Landau level spectrum in bilayer graphene and the observable inter-Landau level transitions when they are studied as a function of high magnetic field at fixed filling factor as measured experimentally in [E.A. Henriksen, Z. Jiang, L.-C. Tung, M.E. Schwartz, M. Takita, Y.-J. Wang, P. Kim, and H.L. Stormer, Phys. Rev. Lett. 100 (2008), 087403]. We also analyse the magneto–optical spectra of bilayer flakes in the photon-energy range corresponding to transitions between degenerate and split bands of bilayers.