Petrologic and oxygen-isotopic investigations of eucritic and anomalous mafic achondrites

The most common asteroidal igneous meteorites are eucrite-type basalts and gabbros rocks composed of ferroan pigeonite and augite, calcic plagioclase, silica, ilmenite, troilite, Ca-phosphate, chromite and Fe-metal. These rocks are thought to have formed on a single asteroid along with howardites and diogenites (HEDs). However, Northwest Africa (NWA) 011 is mineralogically identical to eucrites, but has an O-isotopic composition distinct from them and was derived from a different asteroid. Modern analyses with higher precision have shown that some eucrites have smaller O-isotopic differences that are nevertheless well-resolved from the group mean

Non-Abelian (p,q) Strings in the Warped Deformed Conifold

We calculate the tension of $(p,q)$-strings in the warped deformed conifold using the non-Abelian DBI action. In the large flux limit, we find exact agreement with the recent expression obtained by Firouzjahi, Leblond and Henry-Tye up to and including order $1/M^2$ terms if $q$ is also taken to be large. Furthermore using the finite $q$ prescription for the symmetrised trace operation we anticipate the most general expression for the tension valid for any $(p,q)$. We find that even in this instance, corrections to the tension scale as $1/M^2$ which is not consistent with simple Casimir scaling.Comment: 18 pages, Latex, 1 figure; Added a discussion of the case when the warp factor parameter $b\neq 1$ and typos correcte

Three-Body approach to the K^- d Scattering Length in Particle Basis

We report on the first calculation of the scattering length A_{K^-d} based on a relativistic three-body approach where the two-body input amplitudes coupled to the Kbar N channels have been obtained with the chiral SU(3) constraint, but with isospin symmetry breaking effects taken into account. Results are compared with a recent calculation applying a similar set of two-body amplitudes,based on the fixed center approximation, considered as a good approximation for a loosely bound target, and for which we find significant deviations from the exact three-body results. Effects of the hyperon-nucleon interaction, and deuteron $D$-wave component are also evaluated.Comment: 5 pages, Submitted to Phys. Rev.

Delta rho pi interaction leading to N* and Delta* resonances

We have performed a calculation for the three body $\Delta \rho \pi$ system by using the fixed center approximation to Faddeev equations, taking the interaction between $\Delta$ and $\rho$, $\Delta$ and$\pi$, and $\rho$ and $\pi$ from the chiral unitary approach. We find several peaks in the modulus squared of the three-body scattering amplitude, indicating the existence of resonances, which can be associated to known $I=1/2, 3/2$ and $J^P=1/2^+, 3/2^+$ and $5/2^+$ baryon states.Comment: Presented at the 21st European Conference on Few-Body Problems in Physics, Salamanca, Spain, 30 August - 3 September 201

Nucleus-mediated spin-flip transitions in GaAs quantum dots

Spin-flip rates in GaAs quantum dots can be quite slow, thus opening up the possibilities to manipulate spin states in the dots. We present here estimations of inelastic spin-flip rates mediated by hyperfine interaction with nuclei. Under general assumptions the nucleus mediated rate is proportional to the phonon relaxation rate for the corresponding non-spin-flip transitions. The rate can be accelerated in the vicinity of a singlet-triplet excited states crossing. The small proportionality coefficient depends inversely on the number of nuclei in the quantum dot. We compare our results with known mechanisms of spin-flip in $GaAs$ quantum dot.Comment: RevTex 4 pages, 1 figure, submitted to Phys. Rev.

MEK and PI3K-AKT inhibitors synergistically block activated IL7 receptor signaling in T-cell acute lymphoblastic leukemia

We identified mutations in the IL7Ra gene or in genes encoding the downstream signaling molecules JAK1, JAK3, STAT5B, N-RAS, K-RAS, NF1, AKT and PTEN in 49% of patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL). Strikingly, these mutations (except RAS/NF1) were mutually exclusive, suggesting that they each cause the aberrant activation of a common downstream target. Expressing these mutant signaling molecules—but not their wild-type counterparts—rendered Ba/F3 cells independent of IL3 by activating the RAS-MEK-ERK and PI3K-AKT pathways. Interestingly, cells expressing either IL7Ra or JAK mutants are sensitive to JAK inhibitors, but respond less robustly to inhibitors of the downstream RAS-MEK-ERK and PI3K-AKT-mTOR pathways, indicating that inhibiting only one downstream pathway is not sufficient. Here, we show that inhibiting both the MEK and PI3K-AKT pathways synergistically prevents the proliferation of BaF3 cells expressing mutant IL7Ra, JAK and RAS. Furthermore, combined inhibition of MEK and PI3K/AKT was cytotoxic to samples obtained from 6 out of 11 primary T-ALL patients, including 1 patient who had no mutations in the IL7R signaling pathway. Taken together, these results suggest that the potent cytotoxic effects of inhibiting both MEK and PI3K/AKT should be investigated further as a therapeutic option using leukemia xenograft models.Leukemia advance online publication, 13 May 2016; doi:10.1038/leu.2016.83

Initial State Interactions for K−K^--Proton Radiative Capture

The effects of the initial state interactions on the $K^--p$ radiative capture branching ratios are examined and found to be quite sizable. A general coupled-channel formalism for both strong and electromagnetic channels using a particle basis is presented, and applied to all the low energy $K^--p$ data with the exception of the {\it 1s} atomic level shift. Satisfactory fits are obtained using vertex coupling constants for the electromagnetic channels that are close to their expected SU(3) values.Comment: 16 pages, uses revte

Systematic study of the effect of short range correlations on the form factors and densities of s-p and s-d shell nuclei

Analytical expressions of the one- and two-body terms in the cluster expansion of the charge form factors and densities of the s-p and s-d shell nuclei with N=Z are derived. They depend on the harmonic oscillator parameter b and the parameter $\beta$ which originates from the Jastrow correlation function. These expressions are used for the systematic study of the effect of short range correlations on the form factors and densities and of the mass dependence of the parameters b and $\beta$. These parameters have been determined by fit to the experimental charge form factors. The inclusion of the correlations reproduces the experimental charge form factors at the high momentum transfers ($q\geq 2 1/fm$). It is found that while the parameter $\beta$ is almost constant for the closed shell nuclei, $^4$He, $^{16}$O and $^{40}$Ca, its values are larger (less correlated systems) for the open shell nuclei, indicating a shell effect in the closed shell nuclei.Comment: Latex, 21 pages, 6 figures, 1 tabl

IL-7 Receptor Mutations and Steroid Resistance in Pediatric T cell Acute Lymphoblastic Leukemia: A Genome Sequencing Study

Background: Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer and the leading cause of cancer-related mortality in children. T cell ALL (T-ALL) represents about 15% of pediatric ALL cases and is considered a high-risk disease. T-ALL is often associated with resistance to treatment, including steroids, which are currently the cornerstone for treating ALL; moreover, initial steroid response strongly predicts survival and cure. However, the cellular mechanisms underlying steroid resistance in T-ALL patients are poorly understood. In this study, we combined various genomic datasets in order to identify candidate genetic mechanisms underlying steroid resistance in children undergoing T-ALL treatment. Methods and Findings: We performed whole genome sequencing on paired pre-treatment (diagnostic) and post-treatment (remission) samples from 13 patients, and targeted exome sequencing of pre-treatment samples from 69 additional T-ALL patients. We then integrated mutation data with copy number data for 151 mutated genes, and this integrated dataset was tested for associations of mutations with clinical outcomes and in vitro drug response. Our analysis revealed that mutations in JAK1 and KRAS, two genes encoding components of the interleukin 7 receptor (IL7R) signaling pathway, were associated with steroid resistance and poor outcome. We then sequenced JAK1, KRAS, and other genes in this pathway, including IL7R, JAK3, NF1, NRAS, and AKT, in these 69 T-ALL patients and a further 77 T-ALL patients. We identified mutations in 32% (47/146) of patients, the majority of whom had a specific T-ALL subtype (early thymic progenitor ALL or TLX). Based on the outcomes of these patients and their prednisolone responsiveness measured in vitro, we then confirmed that these mutations were associated with both steroid resistance and poor outcome. To explore how these mutations in IL7R signaling pathway genes cause steroid resistance and subsequent poor outcome, we expressed wild-type and mutant IL7R signaling molecules in two steroid-sensitive T-ALL cell lines (SUPT1 and P12 Ichikawa cells) using inducible lentiviral expression constructs. We found that expressing mutant IL7R, JAK1, or NRAS, or wild-type NRAS or AKT, specifically induced steroid resistance without affecting sensitivity to vincristine or L-asparaginase. In contrast, wild-type IL7R, JAK1, and JAK3, as well as mutant JAK3 and mutant AKT, had no effect. We then performed a functional study to examine the mechanisms underlying steroid resistance and found that, rather than changing the steroid receptor’s ability to activate downstream targets, steroid resistance was associated with strong activation of MEK-ERK and AKT, downstream components of the IL7R signaling pathway, thereby inducing a robust antiapoptotic response by upregulating MCL1 and BCLXL expression. Both the MEK-ERK and AKT pathways also inactivate BIM, an essential molecule for steroid-induced cell death, and inhibit GSK3B, an important regulator of proapoptotic BIM. Importantly, treating our cell lines with IL7R signaling inhibitors restored steroid sensitivity. To address clinical relevance, we treated primary T-ALL cells obtained from 11 patients with steroids either alone or in combination with IL7R signaling inhibitors; we found that including a MEK, AKT, mTOR, or dual PI3K/mTOR inhibitor strongly increased steroid-induced cell death. Therefore, combining these inhibitors with steroid treatment may enhance steroid sensitivity in pat