Nelarabine in the Treatment of Refractory T-Cell Malignancies

Nelarabine is a nucleoside analog indicated for the treatment of adult and pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL) that is refractory or has relapsed after treatment with at least two chemotherapy regimens. After being first synthesized in the late 1970s and receiving FDA approval in 2005, the appropriate use of nelarabine for refractory hematologic malignancies is still being elucidated. Nelarabine is the prodrug of 9-β-D-arabinofuranosylguanine (ara-G) which when phosphorylated intracellularly to ara-G triphosphate (ara-GTP), preferentially accumulates in cancerous T-cells. Dose-dependent toxicities, including neurotoxicity and myelosuppression, have been documented and may, in turn, limit the ability to appropriately treat the diagnosed malignancy. This article will summarize the pharmacologic properties of nelarabine and will address the current place in therapy nelarabine holds based upon the results of the available clinical trials to date

Electronic Structure of Calcium Hexaboride within the Weighted Density Approximation

We report calculations of the electronic structure of CaB$_6$ using the weighted density approximation (WDA) to density functional theory. We find a semiconducting band structure with a sizable gap, in contrast to local density approximation (LDA) results, but in accord with recent experimental data. In particular, we find an $X$-point band gap of 0.8 eV. The WDA correction of the LDA error in describing the electronic structure of CaB$_6$ is discussed in terms of the orbital character of the bands and the better cancelation of self-interactions within the WDA.Comment: 1 figur

Anomalous NMR Spin-Lattice Relaxation in SrB_{6} and Ca_{1-x}La_{x}B_{6}

We report the results of {11}B nuclear magnetic resonance (NMR) measurements of SrB_{6} and Ca_{0.995}La_{0.05}B_{6} below room temperature. Although the electrical resistivities of these two materials differ substantially, their {11}B-NMR responses exhibit some strikingly common features. Both materials exhibit ferromagnetic order, but their {11}B-NMR spectra reveal very small hyperfine fields at the Boron sites. The spin lattice relaxation T_{1}^{-1} varies considerably with external field but changes with temperature only below a few K. We discuss these unusual results by considering various different scenarios for the electronic structure of these materials.Comment: Accepted for publication in Phys. Rev. B Rapid communication, 4 pages, 3 figures. This manuscript replaces an earlier version and includes some minor changes in the text and in Fig.

Magnetism in systems with various dimensionality: A comparison between Fe and Co

A systematic ab initio study is performed for the spin and orbital moments and for the validity of the sum rules for x-ray magnetic circular dichroism for Fe systems with various dimensionality (bulk, Pt-supported monolayers and monatomic wires, free-standing monolayers and monatomic wires). Qualitatively, the results are similar to those for the respective Co systems, with the main difference that for the monatomic Fe wires the term in the spin sum rule is much larger than for the Co wires. The spin and orbital moments induced in the Pt substrate are also discussed.Comment: 4 page

Charge dynamics and "ferromagnetism" of A1-xLaxB6 (A=Ca and Sr)

Ferromagnetism has been reported recently in La-doped alkaline-earth hexaborides, A1-xLaxB6 (A=Ca, Sr, and Ba). We have performed the reflectivity, Hall resistivity, and magnetization measurements of A1-xLaxB6. The results indicate that A1-xLaxB6 can be regarded as a simple doped semimetal, with no signature of an excitonic state as suggested by several theories. It is also found that the surface of as-grown samples (10 micrometer in thickness) has a different electronic structure from a bulk one, and a fairly large number of paramagnetic moments are confined in this region. After eliminating these paramagnetic moments at the surface, we could not find any evidence of an intrinsic ferromagnetic moment in our samples, implying the possibility that the ferromagnetism of A1-xLaxB6 reported so far is neither intrinsic.Comment: 7 pages, 8 figure

Fermi Surface Measurements on the Low Carrier Density Ferromagnet Ca1-xLaxB6 and SrB6

Recently it has been discovered that weak ferromagnetism of a dilute 3D electron gas develops on the energy scale of the Fermi temperature in some of the hexaborides; that is, the Curie temperature approximately equals the Fermi temperature. We report the results of de Haas-van Alphen experiments on two concentrations of La-doped CaB6 as well as Ca-deficient Ca1-dB6 and Sr-deficient Sr1-dB6. The results show that a Fermi surface exists in each case and that there are significant electron-electron interactions in the low density electron gas.Comment: 4 pages, 5 figures, submitted to PR

Theory of High \tc Ferromagnetism in SrB6SrB_6 family: A case of Doped Spin-1 Mott insulator in a Valence Bond Solid Phase

Doped divalent hexaborides such as $Sr_{1-x}La_xB_6$ exhibit high \tc ferromagnetism. We isolate a degenerate pair of $2p$-orbitals of boron with two valence electrons, invoke electron correlation and Hund coupling, to suggest that the undoped state is better viewed as a spin-1 Mott insulator; it is predicted to be a type of 3d Haldane gap phase with a spin gap $\sim 0.1 eV$, much smaller than the charge gap of $> 1.0 eV$ seen in ARPES. The experimentally seen high \tc `ferromagnetism' is argued to be a complex magnetic order in disguise - either a canted 6-sublattice AFM ($\approx 120^0$) order or its quantum melted version, a chiral spin liquid state, arising from a type of double exchange mechanism.Comment: 4 pages, 2 figures; minor corrections, references adde

Extreme Electron-Phonon Coupling in Boron-based Layered Superconductors

The phonon-mode decomposition of the electron-phonon coupling in the MgB2-like system Li_{1-x}BC is explored using first principles calculations. It is found that the high temperature superconductivity of such systems results from extremely strong coupling to only ~2% of the phonon modes. Novel characteristics of E_2g branches include (1) ``mode lambda'' values of 25 and greater compared to a mean of $\sim 0.4$ for other modes, (2) a precipitous Kohn anomaly, and (3) E_2g phonon linewidths within a factor of ~2 of the frequency itself, indicating impending breakdown of linear electron-phonon theory. This behavior in borne out by recent inelastic x-ray scattering studies of MgB2 by Shukla et al.Comment: 4 two-column pages, 4 figures. Equations simplified. Figure 4 changed. Comparison with new data include

Cryo soft X ray tomography as a quantitative three dimensional tool to model nanoparticle cell interaction

Background Recent advances in nanoparticle design have generated new possibilities for nano biotechnology and nano medicine. Here we used cryo soft X ray tomography cryo SXT to collect comprehensive three dimensional 3D data to characterise the interaction of superparamagnetic iron oxide nanoparticles SPION with a breast cancer cell line. Results We incubated MCF 7 a human breast cancer cell line from 0 to 24 h with SPION 15 nm average diameter, coated with dimercaptosuccinic acid , a system that has been studied previously using various microscopy and bulk techniques. This system facilitates the validation and contextualization of the new 3D data acquired using the cryo SXT based approach. After vitrification, samples tested by correlative cryo epifluorescent microscopy showed SPION accumulation in acidic vesicles related to the endocytic pathway. Microscopy grids bearing MCF 7 cells were then analysed by cryo SXT to generate whole cell volume 3D maps. Cryo SXT is an emerging technique that benefits from high X ray penetration into the biological material to image close to native vitrified cells at nanometric resolution with no chemical fixation or staining agents. This unique possibility of obtaining 3D information from whole cells allows quantitative statistical analysis of SPION containing vesicle SCV accumulation inside cells, including vesicle number and size, distances between vesicles, and their distance from the nucleus. Conclusions Correlation between fluorescent microscopy, cryo SXT and transmission electron microscopy allowed us to identify SCV and to generate 3D data for statistical analysis of SPION cell interaction. This study supports continuous transfer of the internalized SPION from the plasma membrane to an accumulation area near the cell nucleus. Statistical analysis showed SCV increase in number and size concomitant with longer incubation times, and therefore an increase in their accumulated volume within the cell. This cumulative effect expands the accumulation area and cell organelles such as mitochondria are consequently displaced to the periphery. Our 3D cryo SXT approach demonstrates that a comprehensive quantitative description of SPION cell interaction is possible, which will serve as a basis for metal based nanoparticle design and for selection of those best suited for hyperthermia treatment, drug delivery and image diagnosis in nanobiomedicin

Physical origin of the buckling in CuO2_2: Electron-phonon coupling and Raman spectra

It is shown theoretically that the buckling of the CuO$_{2}$ planes in certain cuprate systems can be explained in terms of an electric field across the planes which originates from different valences of atoms above and below the plane. This field results also in a strong coupling of the Raman-active out-of-phase vibration of the oxygen atoms ($B_{1g}$ mode) to the electronic charge transfer between the two oxygens in the CuO$_{2}$ plane. Consequently, the electric field can be deduced from the Fano-type line shape of the $B_{1g}$ phonon. Using the electric field estimated from the electron-phonon coupling the amplitude of the buckling is calculated and found to be in good agreement with the structural data. Direct experimental support for the idea proposed is obtained in studies of YBa$_{2}$Cu$_{3}$O$_{6+x}$ and Bi$_{2}$Sr$_{2}$(Ca$_{1-x}$Y$_{x}$)Cu$_{2}$O$_{8}$ with different oxygen and yttrium doping, respectively, including antiferromagnetic samples. In the latter compound, symmetry breaking by replacing Ca partially by Y leads to an enhancement of the electron-phonon coupling by an order of magnitude.Comment: 12 pages, 4 figures, and 1 tabl