X-ray Scattering Study of the spin-Peierls transition and soft phonon behavior in TiOCl

We have studied the S=1/2 quasi-one-dimensional antiferromagnet TiOCl using single crystal x-ray diffraction and inelastic x-ray scattering techniques. The Ti ions form staggered spin chains which dimerize below Tc1 = 66 K and have an incommensurate lattice distortion between Tc1 and Tc2 = 92 K. Based on our measurements of the intensities, wave vectors, and harmonics of the incommensurate superlattice peaks, we construct a model for the incommensurate modulation. The results are in good agreement with a soliton lattice model, though some quantitative discrepancies exist near Tc2. The behavior of the phonons has been studied using inelastic x-ray scattering with ~2 meV energy resolution. For the first time, a zone boundary phonon which softens at the spin-Peierls temperature Tsp has been observed. Our results show reasonably good quantitative agreement with the Cross-Fisher theory for the phonon dynamics at wave vectors near the zone boundary and temperatures near Tsp. However, not all aspects of the data can be described, such as the strong overdamping of the soft mode above Tsp. Overall, our results show that TiOCl is a good realization of a spin-Peierls system, where the phonon softening allows us to identify the transition temperature as Tsp=Tc2=92 KComment: 14 pages, 14 figure

Instanton induced charged fermion and neutrino masses in a minimal Standard Model scenario from intersecting D-branes

String instanton Yukawa corrections from Euclidean D-branes are investigated in an effective Standard Model theory obtained from the minimal U(3)xU(2)xU(1) D-brane configuration. In the case of the minimal chiral and Higgs spectrum, it is found that superpotential contributions are induced by string instantons for the perturbatively forbidden entries of the up and down quark mass matrices. Analogous non-perturbative effects generate heavy Majorana neutrino masses and a Dirac neutrino texture with factorizable Yukawa couplings. For this latter case, a specific example is worked out where it is shown how this texture can reconcile the neutrino data.Comment: 17 pages, 3 figure

The Half-lives of 132^{132}La and 135^{135}La

The half-lives of $^{135}$La and $^{132}$La were determined via gamma spectroscopy and high-precision ionization chamber measurements. The results are 18.930(6) h for $^{135}$La and 4.59(4) h for $^{132}$La compared to the previously compiled values of 19.5(2) h and 4.8(2) h, respectively. The new results represent an improvement in the precision and accuracy of both values. These lanthanum isotopes comprise a medically interesting system with positron emitter $^{132}$La and Auger electron emitter $^{135}$La forming a matched pair for internal diagnostics and therapeutics. The precise half-lives are necessary for proper evaluation of their value in medicine and for a more representative tabulation of nuclear data.Comment: 11 pages, 3 figure

Adaptive upregulation of FOXD3 and resistance to PLX4032/4720-induced cell death in mutant B-RAF melanoma cells.

Melanoma cells driven by mutant v-raf murine sarcoma viral oncogene homolog B1 (B-RAF) are highly resistant to chemotherapeutic treatments. Recent phase 1 results with PLX4032/RG7204/vemurafenib, which selectively inhibits B-RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)1/2 signaling in mutant B-RAF cells, has given encouragement to this struggling field. Nearly all patients in the phase 1-3 studies saw at least some response and the overall response rates ranged from 48 and 81%. However, despite initial tumor shrinkage, most responders in the trial experienced tumor relapse over time. These findings indicate that both intrinsic and acquired resistance may affect the clinical efficacy of PLX4032. It is critical to optimize PLX4032 activity to improve response rates and understand why some patients with the B-RAF mutation do not respond. We have previously shown that the stemness factor, Forkhead box D3 (FOXD3), is upregulated following inhibition of B-RAF-MEK signaling in mutant B-RAF melanoma cells. Here, we show that upregulation of FOXD3 following treatment with PLX4032 and PLX4720 (the non-clinical tool compound for PLX4032) confers resistance to cell death. Small interfering RNA-mediated knockdown of FOXD3 significantly enhanced the cell death response after PLX4032/4720 treatment in mutant B-RAF melanoma cell lines. Additionally, upregulation of FOXD3 after PLX4720 treatment was attenuated in non-adherent conditions and correlated with enhanced cell death. Ectopic expression of FOXD3 in non-adherent cells significantly reduced cell death in response to PLX4720 treatment. Together, these data indicate that upregulation of FOXD3 is an adaptive response to RAF inhibitors that promotes a state of drug resistance

Fermion Masses and Mixing in Four and More Dimensions

We give an overview of recent progress in the study of fermion mass and flavor mixing phenomena. Mass matrix ansatze are considered within the SM and SUSY GUTs where some predictive frameworks based on SU(5) and SO(10) are reviewed. We describe a variety of schemes to construct quark mass matrices in extra dimensions focusing on four major classes: models with the SM residing on 3-brane, models with universal extra dimensions, models with split fermions and models with warped extra dimensions. We outline how realistic patterns of quark mass matrices could be derived from orbifold models in heterotic superstring theory. Finally, we address the fermion mass problem in intersecting D-branes scenarios, and present models with D6-branes able to give a good quantitatively description of quark masses and mixing. The role of flavor/CP violation problem as a probe of new physics is emphasized.Comment: a review based on seminars presented by S.K. in different places, 34 pages, late

Solitonic supersymmetry restoration

Q-balls are a possible feature of any model with a conserved, global U(1) symmetry and no massless, charged scalars. It is shown that for a broad class of models of metastable supersymmetry breaking they are extremely influential on the vacuum lifetime and make seemingly viable vacua catastrophically short lived. A net charge asymmetry is not required as there is often a significant range of parameter space where statistical fluctuations alone are sufficient. This effect is examined for two supersymmetry breaking scenarios. It is found that models of minimal gauge mediation (which necessarily have a messenger number U(1)) undergo a rapid, supersymmetry restoring phase transition unless the messenger mass is greater than 10^8 GeV. Similarly the ISS model, in the context of direct mediation, quickly decays unless the perturbative superpotential coupling is greater than the Standard Model gauge couplings.Comment: 17 pages, 3 figures, minor comments added, accepted for publication in JHE

Meta-Stable Brane Configuration with Orientifold 6 Plane

We present the intersecting brane configuration of type IIA string theory corresponding to the meta-stable nonsupersymmetric vacua in four dimensional N=1 supersymmetric SU(N_c) gauge theory with a symmetric flavor, a conjugate symmetric flavor and fundamental flavors. By studying the previously known supersymmetric M5-brane curve, the M-theory lift for this type IIA brane configuration, which consists of NS5-branes, D4-branes, D6-branes and an orientifold 6-plane, is analyzed.Comment: 21 pp, 3 colored figures; stability arguments added in page 11 and 12, a typo in figure 3 corrected, and to appear in JHE

Role of the Bcl-2 gene family in prostate cancer progression and its implications for therapeutic intervention.

Prostate cancer (PC) is an escalating health burden in the western world. A large number of patients still present with extraprostatic (i.e., T3/T4, N0, M0/M1 or any T category and M1 disease or involved lymph nodes) and therefore incurable disease. Since the work of Huggins in 1940, there have been no major therapeutic advances and androgen ablation remains the best treatment option for extraprostatic androgen-responsive PC. Eighty to ninety percent of PC patients respond well to this form of treatment initially. After a median time of approximately 2 years, however, relapse to an androgen-independent (AI) state occurs, followed by death after a further median 6 months. Androgen ablation is rarely curative. The major molecular defect in extraprostatic and AI PC is the inability of PC cells to initiate apoptosis in response to a variety of stimuli, including different forms of androgen ablation and cytotoxic agents. The balance between cellular proliferation and cell death is regulated by multiple genes or families of genes through the cell cycle. The exact mechanisms governing this intricate and complex process are as yet not fully understood. One family of genes involved in cell survival/death control is the Bcl-2 gene family, which consists of homologous proteins that function to regulate distal and crucial commitment steps of the apoptotic pathway. The Bcl-2 family constitutes both agonists and antagonists of apoptosis that function at least in part through protein-protein interactions between various members of the family. The final outcome depends on the relative ratio of death agonists and antagonists. Bcl-2 expression has been closely associated with the AI phenotype of PC. Cytotoxic chemotherapy may be used as palliative therapy in AI PC but has not been found effective. Most chemotherapeutic cytotoxic agents induce apoptosis in cancer cells by direct and indirect action on the cell cycle. In vitro and in vivo studies have established that Bcl-2 expression confers an antiapoptotic activity against androgen withdrawal and cytotoxic chemotherapy. It thus offers a tempting potential target for therapeutic manipulations of PC