A Model of Graceful Exit in String Cosmology

We construct, for the first time, a model of graceful exit transition from a dilaton-driven inflationary phase to a decelerated Friedman-Robertson-Walker era. Exploiting a demonstration that classical corrections can stabilize a high curvature string phase while the evolution is still in the weakly coupled regime, we show that if additional terms of the type that may result from quantum corrections to the string effective action exist, and induce violation of the null energy condition, then evolution towards a decelerated Friedman-Robertson-Walker phase is possible. We also observe that stabilizing the dilaton at a fixed value, either by capture in a potential minimum or by radiation production, may require that these quantum corrections are turned off, perhaps by non-perturbative effects or higher order contributions which overturn the null energy condition violation.Comment: 17 pages including 9 figures, RevTeX. Uses epsfi

Immunology of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) leading to demyelination, axonal damage, and progressive neurologic disability. The development of MS is influenced by environmental factors, particularly the Epstein-Barr virus (EBV), and genetic factors, which include specific HLA types, particularly DRB1*1501-DQA1*0102-DQB1*0602, and a predisposition to autoimmunity in general. MS patients have increased circulating T-cell and antibody reactivity to myelin proteins and gangliosides. It is proposed that the role of EBV is to infect autoreactive B cells that then seed the CNS and promote the survival of autoreactive T cells there. It is also proposed that the clinical attacks of relapsing-remitting MS are orchestrated by myelin-reactive T cells entering the white matter of the CNS from the blood, and that the progressive disability in primary and secondary progressive MS is caused by the action of autoantibodies produced in the CNS by ­meningeal lymphoid follicles with germinal centers

Combinatorial Markov chains on linear extensions

We consider generalizations of Schuetzenberger's promotion operator on the set L of linear extensions of a finite poset of size n. This gives rise to a strongly connected graph on L. By assigning weights to the edges of the graph in two different ways, we study two Markov chains, both of which are irreducible. The stationary state of one gives rise to the uniform distribution, whereas the weights of the stationary state of the other has a nice product formula. This generalizes results by Hendricks on the Tsetlin library, which corresponds to the case when the poset is the anti-chain and hence L=S_n is the full symmetric group. We also provide explicit eigenvalues of the transition matrix in general when the poset is a rooted forest. This is shown by proving that the associated monoid is R-trivial and then using Steinberg's extension of Brown's theory for Markov chains on left regular bands to R-trivial monoids.Comment: 35 pages, more examples of promotion, rephrased the main theorems in terms of discrete time Markov chain

First-line palliative HER2-targeted therapy in HER2-positive metastatic breast cancer is less effective after previous adjuvant trastuzumab-based therapy

Background. Survival of patients with human epidermal growth receptor 2 (HER2)-positive metastatic breast cancer (MBC) has improved dramatically since trastuzumab has become available, although the disease eventually progresses in most patients. This study investigates the outcome (overall survival [OS] and time to next treatment [TNT]) in MBC patients pretreated with trastuzumab in the adjuvant setting (TP-group) compared with trastuzumab-näive patients (TN-group) in order to investigate the possibility of trastuzumab resistance. Patients and Methods. Patients treated with first-line HER2-targeted- containing chemotherapy were eligible for the study. A power analysis was performed to estimate the minimum size of the TP-group. OS and TNT were estimated using Kaplan-Meier curves andmultivariable Cox proportional hazards models. Results. Between January 1, 2000, and June 1, 2014, 469 patients were included, of whom 82 were in the TP-group and 387 were in the TN-group. Median OS and TNT were significantly worse in the TP-group compared with the TN-group (17 vs. 30 months, adjusted hazard ratio [HR] 1.84 [1.15-2.96], p5.01 and 7 vs. 13 months, adjusted HR 1.65 [1.06-2.58], p5.03) after adjustment for age, year of diagnosis, diseasefree interval, hormone receptor status, metastatic site, and cytotoxic regimens. Conclusion. First-line trastuzumab-containing treatment regimens are less effective in patients with failure of adjuvant trastuzumab compared with trastuzumab-näive patients and might be due to trastuzumab resistance. The impact of trastuzumab resistance on the response on dual HER2 blockade with trastuzumab and pertuzumab and how resistance mechanisms can be used in the optimization of HER2-targeted treatment lines need further investigation.</p

No Association Between MTHFR A1298C and MTRR A66G Polymorphisms, and MS in an Australian Cohort

Multiple sclerosis (MS) is a complex neurological disease that affects the central nervous system (CNS) resulting in debilitating neuropathology. Pathogenesis is primarily defined by CNS inflammation and demyelination of nerve axons. Methionine synthase reductase (MTRR) is an enzyme that catalyzes the remethylation of homocysteine (Hcy) to methionine via cobalamin and folate dependant reactions. Cobalamin acts as an intermediate methyl carrier between methylenetetrahydrofolate reductase (MTHFR) and Hcy. MTRR plays a critical role in maintaining cobalamin in an active form and is consequently an important determinant of total plasma Hcy (pHcy) concentrations. Elevated intracellular pHcy levels have been suggested to play a role in CNS dysfunction, neurodegenerative, and cerebrovascular diseases. Our investigation entailed the genotyping of a cohort of 140 cases and matched controls for MTRR and MTHFR, by restriction length polymorphism (RFLP) techniques. Two polymorphisms: MTRR A66G and MTHFR A1298C were investigated in an Australian age and gender matched case-control study. No significant allelic frequency difference was observed between cases and controls at the α = 0.05 level (MTRR χ^2 = 0.005, P = 0.95, MTHFR χ^2 = 1.15, P = 0.28). Our preliminary findings suggest no association between the MTRR A66G and MTHFR A1298C polymorphisms and MS

Possible origins of macroscopic left-right asymmetry in organisms

I consider the microscopic mechanisms by which a particular left-right (L/R) asymmetry is generated at the organism level from the microscopic handedness of cytoskeletal molecules. In light of a fundamental symmetry principle, the typical pattern-formation mechanisms of diffusion plus regulation cannot implement the "right-hand rule"; at the microscopic level, the cell's cytoskeleton of chiral filaments seems always to be involved, usually in collective states driven by polymerization forces or molecular motors. It seems particularly easy for handedness to emerge in a shear or rotation in the background of an effectively two-dimensional system, such as the cell membrane or a layer of cells, as this requires no pre-existing axis apart from the layer normal. I detail a scenario involving actin/myosin layers in snails and in C. elegans, and also one about the microtubule layer in plant cells. I also survey the other examples that I am aware of, such as the emergence of handedness such as the emergence of handedness in neurons, in eukaryote cell motility, and in non-flagellated bacteria.Comment: 42 pages, 6 figures, resubmitted to J. Stat. Phys. special issue. Major rewrite, rearranged sections/subsections, new Fig 3 + 6, new physics in Sec 2.4 and 3.4.1, added Sec 5 and subsections of Sec

Asymmetric Collision of Two Shock Waves in AdS_5

We consider high energy collisions of two shock waves in AdS_5 as a model of ultrarelativistic nucleus-nucleus collisions in the boundary theory. We first calculate the graviton field produced in the collisions in the NLO and NNLO approximations, corresponding to three- and four-graviton exchanges with the shock waves. We then consider the asymmetric limit where the energy density in one shock wave is much higher than in the other one. In the boundary theory this setup corresponds to proton-nucleus collisions, with the nucleus being the denser of the two shock waves and the proton being the less dense one. Employing the eikonal approximation we find the exact high energy analytic solution for the metric in AdS_5 for the asymmetric collision of two delta-function shock waves. The solution resums all-order graviton exchanges with the "nucleus" shock wave and a single-graviton exchange with the "proton" shock wave. Using the holographic renormalization prescription we read off the energy-momentum tensor of the matter produced in proton-nucleus collisions. We show in explicit detail that in the boundary theory the proton is completely stopped by strong-coupling interactions with the nucleus, in agreement with our earlier results. We also apply the eikonal technique to the asymmetric collision of two unphysical delta-prime shock waves, which we introduced in an earlier work as a means of modeling nuclear collisions with weak coupling initial dynamics. We obtain a surprising result that, for delta-prime shock waves, the multiple bulk graviton exchange series giving the leading energy-dependent contribution to the energy-momentum tensor terminates at the order of two graviton exchanges with the nucleus.Comment: 44 pages, 8 figures; v2: typos corrected, references added; v3: a subsection added, more typos correcte

Large-scale power in the CMB and new physics: An analysis using Bayesian model comparison

Published versio

Effective interaction between helical bio-molecules

The effective interaction between two parallel strands of helical bio-molecules, such as deoxyribose nucleic acids (DNA), is calculated using computer simulations of the "primitive" model of electrolytes. In particular we study a simple model for B-DNA incorporating explicitly its charge pattern as a double-helix structure. The effective force and the effective torque exerted onto the molecules depend on the central distance and on the relative orientation. The contributions of nonlinear screening by monovalent counterions to these forces and torques are analyzed and calculated for different salt concentrations. As a result, we find that the sign of the force depends sensitively on the relative orientation. For intermolecular distances smaller than $6\AA$ it can be both attractive and repulsive. Furthermore we report a nonmonotonic behaviour of the effective force for increasing salt concentration. Both features cannot be described within linear screening theories. For large distances, on the other hand, the results agree with linear screening theories provided the charge of the bio-molecules is suitably renormalized.Comment: 18 pages, 18 figures included in text, 100 bibliog