Quantum effects of a massive 3-form coupled to a Dirac field

We consider the coupling of A_{\mu\nu\rho} to the generic current of matter field, later identified with the spin density current of a Dirac field. In fact, one of the objectives of this paper is to investigate the impact of the quantum fluctuations of A_{\mu\nu\rho} on the effective dynamics of the spinor field. The consistency of the field equations, even at the classical level, requires the introduction of a mass term for A_{\mu\nu\rho}. In this case, the Casimir vacuum pressure includes a contribution that is explicitly dependent on the mass of A_{\mu\nu\rho} and leads us to conclude that the mass term plays the same role as the infrared cutoff needed to regularize the finite volume partition functional previously calculated in the massless case. Remarkably, even in the presence of a mass term, A_{\mu\nu\rho} contains a mixture of massless and massive spin-0 fields so that the resulting equation is still gauge invariant. This is yet another peculiar, but physically relevant property of A_{\mu\nu\rho} since it is reflected in the effective dynamics of the spinor fields and confirms the confining property of A_{\mu\nu\rho} already expected from the earlier calculation of the Wilson loop.Comment: 10 pages, Revtex, no figures; in print on Phys.Rev.D; added new reference

Dynamical Systems approach to Saffman-Taylor fingering. A Dynamical Solvability Scenario

A dynamical systems approach to competition of Saffman-Taylor fingers in a channel is developed. This is based on the global study of the phase space structure of the low-dimensional ODE's defined by the classes of exact solutions of the problem without surface tension. Some simple examples are studied in detail, and general proofs concerning properties of fixed points and existence of finite-time singularities for broad classes of solutions are given. The existence of a continuum of multifinger fixed points and its dynamical implications are discussed. The main conclusion is that exact zero-surface tension solutions taken in a global sense as families of trajectories in phase space spanning a sufficiently large set of initial conditions, are unphysical because the multifinger fixed points are nonhyperbolic, and an unfolding of them does not exist within the same class of solutions. Hyperbolicity (saddle-point structure) of the multifinger fixed points is argued to be essential to the physically correct qualitative description of finger competition. The restoring of hyperbolicity by surface tension is discussed as the key point for a generic Dynamical Solvability Scenario which is proposed for a general context of interfacial pattern selection.Comment: 3 figures added, major rewriting of some sections, submitted to Phys. Rev.

A Universal Vertical Stellar Density Distribution Law for the Galaxy

We reduced the observational logarithmic space densities in the vertical direction up to 8 kpc from the galactic plane, for stars with absolute magnitudes (5,6], (6,7] and [5,10] in the fields #0952+5245 and SA114, to a single exponential density law. One of three parameters in the quadratic expression of the density law corresponds to the local space density for stars with absolute magnitudes in question. There is no need of any definition for scaleheights or population types. We confirm with the arguments of non-discrete thin and thick discs for our Galaxy and propose a single structure up to several kiloparsecs from the galactic plane. The logarithmic space densities evaluated by this law for the ELAIS field fit to the observational ones. Whereas, there are considerable offsets for the logarithmic space densities produced by two sets of classical galactic model parameters from the observational ones, for the same field.Comment: 9 pages, 1 figure and 10 tables, accepted for publication in Astrophysics & Space Scienc

Combined kinase inhibitors of MEK1/2 and either PI3K or PDGFR are efficacious in intracranial triple-negative breast cancer

Background: Triple-negative breast cancer (TNBC), lacking expression of hormone and human epidermal growth factor receptor 2 receptors, is an aggressive subtype that frequently metastasizes to the brain and has no FDA-approved systemic therapies. Previous literature demonstrates mitogen-Activated protein kinase kinase (MEK) pathway activation in TNBC brain metastases. Thus, we aimed to discover rational combinatorial therapies with MEK inhibition, hypothesizing that co-inhibition using clinically available brain-penetrant inhibitors would improve survival in preclinical models of TNBC brain metastases. Methods: Using human-derived TNBC cell lines, synthetic lethal small interfering RNA kinase screens were evaluated with brain-penetrant inhibitors against MEK1/2 (selumetinib, AZD6244) or phosphatidylinositol-3 kinase (PI3K; buparlisib, BKM120). Mice bearing intracranial TNBC tumors (SUM149, MDA-MB-231Br, MDA-MB-468, or MDA-MB-436) were treated with MEK, PI3K, or platelet derived growth factor receptor (PDGFR; pazopanib) inhibitors alone or in combination. Tumors were analyzed by western blot and multiplexed kinase inhibitor beads/mass spectrometry to assess treatment effects. Results: Screens identified MEK+PI3K and MEK+PDGFR inhibitors as tractable, rational combinations. Dual treatment of selumetinib with buparlisib or pazopanib was synergistic in TNBC cells in vitro. Both combinations improved survival in intracranial SUM149 and MDA-MB-231Br, but not MDA-MB-468 or MDA-MB-436. Treatments decreased mitogen-Activated protein kinase (MAPK) and PI3K (Akt) signaling in sensitive (SUM149 and 231Br) but not resistant models (MDA-MB-468). Exploratory analysis of kinome reprogramming in SUM149 intracranial tumors after MEK PI3K inhibition demonstrates extensive kinome changes with treatment, especially in MAPK pathway members. Conclusions: Results demonstrate that rational combinations of the clinically available inhibitors selumetinib with buparlisib or pazopanib may prove to be promising therapeutic strategies for the treatment of some TNBC brain metastases. Additionally, effective combination treatments cause widespread alterations in kinase pathways, including targetable potential resistance drivers

Membrane duality revisited

Just as string T-duality originates from transforming field equations into Bianchi identities on the string worldsheet, so it has been suggested that M-theory U-dualities originate from transforming field equations into Bianchi identities on the membrane worldvolume. However, this encounters a problem unless the target space has dimension D=p+1. We identify the problem to be the nonintegrability of the U-duality transformation assigned to the pull-back map. Just as a double geometry renders manifest the O(D,D) string T-duality, here we show in the case of the M2-brane in D=3 that a generalised geometry renders manifest the SL(3) 7SL(2) U-duality. In the case of M2-brane in D=4, with and without extra target space coordinates, we show that only the GL(4,R) c9R4 subgroup of the expected SL(5,R) U-duality symmetry is realised

LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases

Purpose: HER2 + breast cancer (BC) is an aggressive subtype with high rates of brain metastases (BCBM). Two-thirds of HER2 + BCBM demonstrate activation of the PI3K/mTOR pathway driving resistance to anti-HER2 therapy. This phase II study evaluated everolimus (E), a brain-permeable mTOR inhibitor, trastuzumab (T), and vinorelbine (V) in patients with HER2 + BCBM. Patients and methods: Eligible patients had progressive HER2 + BCBM. The primary endpoint was intracranial response rate (RR); secondary objectives were CNS clinical benefit rate (CBR), extracranial RR, time to progression (TTP), overall survival (OS), and targeted sequencing of tumors from enrolled patients. A two-stage design distinguished intracranial RR of 5% versus 20%. Results: 32 patients were evaluable for toxicity, 26 for efficacy. Intracranial RR was 4% (1 PR). CNS CBR at 6 mos was 27%; at 3 mos 65%. Median intracranial TTP was 3.9 mos (95% CI 2.2–5). OS was 12.2 mos (95% CI 0.6–20.2). Grade 3–4 toxicities included neutropenia (41%), anemia (16%), and stomatitis (16%). Mutations in TP53 and PIK3CA were common in BCBM. Mutations in the PI3K/mTOR pathway were not associated with response. ERBB2 amplification was higher in BCBM compared to primary BC; ERBB2 amplification in the primary BC trended toward worse OS. Conclusion: While intracranial RR to ETV was low in HER2 + BCBM patients, one-third achieved CNS CBR; TTP/OS was similar to historical control. No new toxicity signals were observed. Further analysis of the genomic underpinnings of BCBM to identify tractable prognostic and/or predictive biomarkers is warranted. Clinical Trial: (NCT01305941)

Femtosecond x-ray diffraction reveals a liquid–liquid phase transition in phase-change materials

6 pags., 5 figs.In phase-change memory devices, a material is cycled between glassy and crystalline states. The highly temperature-dependent kinetics of its crystallization process enables application in memory technology, but the transition has not been resolved on an atomic scale. Using femtosecond x-ray diffraction and ab initio computer simulations, we determined the time-dependent pair-correlation function of phase-change materials throughout the melt-quenching and crystallization process. We found a liquid–liquid phase transition in the phase-change materials AgInSbTe and GeSb at 660 and 610 kelvin, respectively. The transition is predominantly caused by the onset of Peierls distortions, the amplitude of which correlates with an increase of the apparent activation energy of diffusivity. This reveals a relationship between atomic structure and kinetics, enabling a systematic optimization of the memory-switching kinetics.F.Q., A.K., M.N., and K.S.T. gratefully acknowledge financial support from the German Research Council through the Collaborative Research Center SFB 1242 project 278162697 (“Non-Equilibrium Dynamics of Condensed Matter in the Time Domain”), project C01 (“Structural Dynamics in Impulsively Excited Nanostructures”), and individual grant So408/9-1, as well as the European Union (7th Framework Programme, grant no. 280555 GO FAST). M.J.S., R.M., and M.W. acknowledge financial support from the German Research Council through the Collaborative Research Center SFB 917 (“Nanoswitches”) and individual grant Ma-5339/2-1. M.J.S., I.R., and R.M. also acknowledge the computational resources granted by JARA-HPC from RWTH Aachen University under project nos. JARA0150 and JARA0183. M.T., A.M.L., and D.A.R. were supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, through the Division of Materials Sciences and Engineering under contract no. DE-AC02-76SF00515. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344. J.L. acknowledges support from the Swedish Research Council. J.S. acknowledges financial support from the Spanish Ministry of Science, Innovation and Universities through research grant UDiSON (TEC2017-82464-R). P.Z. gratefully acknowledges funding by the Humboldt Foundatio

Global conformal anomaly in N=2 string

We show the existence of a global anomaly in the one-loop graphs of N=2 string theory, defined by sewing tree amplitudes, unless spacetime supersymmetry is imposed. The anomaly is responsible for the non-vanishing maximally helicity violating amplitudes. The supersymmetric completion of the N=2 string spectrum is formulated by extending the previous cohomological analysis with an external spin factor; the target space-time spin-statistics of these individual fields in a selfdual background are compatible with previous cohomological analysis as fields of arbitrary spin may be bosonized into one another. We further analyze duality relations between the open and closed string amplitudes and demonstrate this in the supersymmetric extension of the target space-time theory through the insertion of zero-momentum operators.Comment: 29 pages, LaTeX, one figur