A Strategy for Imidazotetrazine Prodrugs with Anti-cancer Activity Independent of MGMT and MMR

The imidazotetrazine ring is an acid-stable precursor and prodrug of highly-reactive alkyl diazonium ions. We have shown that this reactivity can be managed productively in an aqueous system for the generation of aziridinium ions with 96% efficiency. The new compounds are potent DNA alkylators and have antitumor activity independent of the O6-methylguanine-DNA methyltransferase and DNA mismatch repair constraints that limit the use of temozolomide

Exciton localization mechanisms in wurtzite/zinc-blende GaAs nanowires

We investigate the emission properties of excitons in GaAs nanowires containing quantum disks formed by structural alternation between the zinc-blende and wurtzite phases, by means of temperature-dependent photoluminescence. At 10 K the emission from an ensemble of disks is distributed in a band of full width at half maximum ∼30 meV, whereas the emission linewidth for a single disk is 700 μeV. While the disk ensemble emission exhibits an S-shaped temperature dependence, the emission from single quantum disks follows the temperature dependence of the band gap over the whole temperature range. This indicates that intradisk exciton localization on impurities is negligible and that increasing the temperature induces a transfer of excitons from narrow to thick disks along the length of the wires. Our observations of the emission linewidth for single crystal-phase quantum disks show a scattering rate of excitons with acoustic phonons eight times larger than the values usually reported for (Al,Ga)As/GaAs quantum wells. This large scattering rate demonstrates that the electron effective mass in wurtzite GaAs is much heavier than in zinc-blende GaAs and is evidence of coupling between the Γ7 and Γ8 conduction bands of wurtzite GaAs.We acknowledge financial support from the Poynton Cambridge Australia Scholarship and from the European Union Seventh Framework Program under grant agreement No. 265073. A.F.iM. and E.U. acknowledge funding through the Marie Curie Excellence grant SENFED. S.C.B. thanks S.N.F. for funding through the Marie-Heim Vögtlin scheme

From the artificial atom to the Kondo-Anderson model: Orientation-dependent magnetophotoluminescence of charged excitons in InAs quantum dots

We present a magnetophotoluminescence study on neutral and charged excitons confined to InAs/GaAs quantum dots. Our investigation relies on a confocal microscope that allows arbitrary tuning of the angle between the applied magnetic field and the sample growth axis. First, from experiments on neutral excitons and trions, we extract the in-plane and on-axis components of the Landé tensor for electrons and holes in the s shell. Then, based on the doubly negatively charged exciton magnetophotoluminescence, we show that the p-electron wave function spreads significantly into the GaAs barriers. We also demonstrate that the p-electron g factor depends on the presence of a hole in the s shell. The magnetic field dependence of triply negatively charged excitons photoluminescence exhibits several anticrossings, as a result of coupling between the quantum dot electronic states and the wetting layer. Finally, we discuss how the system evolves from a Kondo-Anderson exciton description to the artificial atom model when the orientation of the magnetic field goes from Faraday to Voigt geometry.We acknowledge funding from the EPSRC. B.V.H. also thanks the Hitachi Cambridge Laboratory for additional fund- ing. P.C. acknowledges financial support from the European Union Seventh Framework Programme under Grant agreement No. 265073

Perturbations of nuclear C*-algebras

Kadison and Kastler introduced a natural metric on the collection of all C*-subalgebras of the bounded operators on a separable Hilbert space. They conjectured that sufficiently close algebras are unitarily conjugate. We establish this conjecture when one algebra is separable and nuclear. We also consider one-sided versions of these notions, and we obtain embeddings from certain near inclusions involving separable nuclear C*-algebras. At the end of the paper we demonstrate how our methods lead to improved characterisations of some of the types of algebras that are of current interest in the classification programme.Comment: 45 page

Effect of crystalline disorder on quantum tunneling in the single-molecule magnet Mn12 benzoate

10 páginas, 9 figuras, 1 tabla.-- PACS number(s): 75.45.+j, 75.50.Xx, 75.60.Jk, 75.50.Kj.-- et al.We report a detailed study of the effects that crystalline disorder has on the magnetic relaxation and quantum tunneling of Mn12 benzoate clusters. Thanks to the absence of interstitial molecules in the crystal structure of this molecular compound, we have been able to isolate the influence of long-range crystalline disorder. For this, we compare results obtained under two extreme situations: a crystalline sample and a nearly amorphous material. The results show that crystalline disorder affects little the anisotropy, magnetic relaxation, and quantum tunneling of these materials. It follows that disorder is not a necessary ingredient for the existence of magnetic quantum tunneling. The results unveil, however, a subtle influence of crystallinity via the modification of the symmetry of dipole-dipole interactions. The faster tunneling rates measured for the amorphous material are accounted for by a narrower distribution of dipolar bias in this material, as compared with the crystalline sample.This work has been partly funded by Grants No. MAT2009-13977-C03, No. MAT2008-06542- C04, and No. CSD2007-00010 from the Spanish Ministerio de Ciencia e Innovación, and NABISUP from DGA. We acknowledge funding from Acción Integrada under Grant No. HA2006-0051 and the Network of Excellence MAGMANet. J.v.S and S.D. acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG) and the DAAD. Ch.C. and I.I. acknowledge the Spanish Ministerio de Ciencia e Innovación.Peer reviewe

Temperature-dependence of exciton radiative recombination in (Al,Ga)N/GaN quantum wells grown on a-plane GaN substrates

This article presents the dynamics of excitons in a-plane (Al,Ga)N/GaN single quantum wells of various thicknesses grown on bulk GaN substrates. For all quantum well samples, recombination is observed to be predominantly radiative in the low-temperature range. At higher temperatures, the escape of charge carriers from the quantum well to the (Al,Ga)N barriers is accompanied by a reduction in internal quantum efficiency. Based on the temperature-dependence of time-resolved photoluminescence experiments, we also show how the local disorder affects the exciton radiative lifetime at low temperature and the exciton non-radiative lifetime at high temperature.We acknowledge financial support from the Swiss National Science Foundation through Project No. 129715 and from the Polish National Science Center (Project DEC-2011/ 03/B/ST3/02647). The work was partially supported by the European Union within European Regional Development Fund through Innovative Economy Grant No. POIG.01.01.02-00-008/08. P.C. also acknowledges financing from the European Union Seventh Framework Program under grant agreement No. 265073

Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer

DC Bead is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40–45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC50 for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 lM compared to 28.1 and 19.2 lM for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 & 30 mg ml-1, like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 & 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3–6.6 mg were shown to be well tolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83–1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2–0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity

Reversals in nature and the nature of reversals

The asymmetric shape of reversals of the Earth's magnetic field indicates a possible connection with relaxation oscillations as they were early discussed by van der Pol. A simple mean-field dynamo model with a spherically symmetric $\alpha$ coefficient is analysed with view on this similarity, and a comparison of the time series and the phase space trajectories with those of paleomagnetic measurements is carried out. For highly supercritical dynamos a very good agreement with the data is achieved. Deviations of numerical reversal sequences from Poisson statistics are analysed and compared with paleomagnetic data. The role of the inner core is discussed in a spectral theoretical context and arguments and numerical evidence is compiled that the growth of the inner core might be important for the long term changes of the reversal rate and the occurrence of superchrons.Comment: 24 pages, 12 figure

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

Two-Particle-Self-Consistent Approach for the Hubbard Model

Even at weak to intermediate coupling, the Hubbard model poses a formidable challenge. In two dimensions in particular, standard methods such as the Random Phase Approximation are no longer valid since they predict a finite temperature antiferromagnetic phase transition prohibited by the Mermin-Wagner theorem. The Two-Particle-Self-Consistent (TPSC) approach satisfies that theorem as well as particle conservation, the Pauli principle, the local moment and local charge sum rules. The self-energy formula does not assume a Migdal theorem. There is consistency between one- and two-particle quantities. Internal accuracy checks allow one to test the limits of validity of TPSC. Here I present a pedagogical review of TPSC along with a short summary of existing results and two case studies: a) the opening of a pseudogap in two dimensions when the correlation length is larger than the thermal de Broglie wavelength, and b) the conditions for the appearance of d-wave superconductivity in the two-dimensional Hubbard model.Comment: Chapter in "Theoretical methods for Strongly Correlated Systems", Edited by A. Avella and F. Mancini, Springer Verlag, (2011) 55 pages. Misprint in Eq.(23) corrected (thanks D. Bergeron