Virus shapes and buckling transitions in spherical shells

We show that the icosahedral packings of protein capsomeres proposed by Caspar and Klug for spherical viruses become unstable to faceting for sufficiently large virus size, in analogy with the buckling instability of disclinations in two-dimensional crystals. Our model, based on the nonlinear physics of thin elastic shells, produces excellent one parameter fits in real space to the full three-dimensional shape of large spherical viruses. The faceted shape depends only on the dimensionless Foppl-von Karman number \gamma=YR^2/\kappa, where Y is the two-dimensional Young's modulus of the protein shell, \kappa is its bending rigidity and R is the mean virus radius. The shape can be parameterized more quantitatively in terms of a spherical harmonic expansion. We also investigate elastic shell theory for extremely large \gamma, 10^3 < \gamma < 10^8, and find results applicable to icosahedral shapes of large vesicles studied with freeze fracture and electron microscopy.Comment: 11 pages, 12 figure

A perspective on the landscape problem

I discuss the historical roots of the landscape problem and propose criteria for its successful resolution. This provides a perspective to evaluate the possibility to solve it in several of the speculative cosmological scenarios under study including eternal inflation, cosmological natural selection and cyclic cosmologies.Comment: Invited contribution for a special issue of Foundations of Physics titled: Forty Years Of String Theory: Reflecting On the Foundations. 31 pages, no figure

Gravity-Driven Acceleration of the Cosmic Expansion

It is shown here that a dynamical Planck mass can drive the scale factor of the universe to accelerate. The negative pressure which drives the cosmic acceleration is identified with the unusual kinetic energy density of the Planck field. No potential nor cosmological constant is required. This suggests a purely gravity driven, kinetic inflation. Although the possibility is not ruled out, the burst of acceleration is often too weak to address the initial condition problems of cosmology. To illustrate the kinetic acceleration, three different cosmologies are presented. One such example, that of a bouncing universe, demonstrates the additional feature of being nonsingular. The acceleration is also considered in the conformally related Einstein frame in which the Planck mass is constant.Comment: 23 pages, LaTex, figures available upon request, (revisions include added references and comment on inflation) CITA-94-1

The universe formation by a space reduction cascade with random initial parameters

In this paper we discuss the creation of our universe using the idea of extra dimensions. The initial, multidimensional Lagrangian contains only metric tensor. We have found many sets of the numerical values of the Lagrangian parameters corresponding to the observed low-energy physics of our universe. Different initial parameters can lead to the same values of fundamental constants by the appropriate choice of a dimensional reduction cascade. This result diminishes the significance of the search for the 'unique' initial Lagrangian. We also have obtained a large number of low-energy vacua, which is known as a 'landscape' in the string theory.Comment: 17 pages, 1 figur

A Study of the 't Hooft Model with the Overlap Dirac Operator

We present the results of an exploratory numerical study of two dimensional QCD with overlap fermions. We have performed extensive simulations for U(N_c) and SU(N_c) color groups with N_c=2, 3, 4 and coupling constants chosen to satisfy the 't Hooft condition g^2 N_c =const=4/3. We have computed the meson spectrum and decay constants, the topological susceptibility and the chiral condensate. For U(N_c) gauge groups, our results indicate that the Witten-Veneziano relation is satisfied within our statistical errors and that the chiral condensate for N_f=1 is compatible with a non-zero value. Our results exhibit universality in N_c and confirm once more the excellent chiral properties of the overlap-Dirac operator.Comment: 18 pages, 4 figure

Topological defects: A problem for cyclic universes?

We study the behaviour of cosmic string networks in contracting universes, and discuss some of their possible consequences. We note that there is a fundamental time asymmetry between defect network evolution for an expanding universe and a contracting universe. A string network with negligible loop production and small-scale structure will asymptotically behave during the collapse phase as a radiation fluid. In realistic networks these two effects are important, making this solution only approximate. We derive new scaling solutions describing this effect, and test them against high-resolution numerical simulations. A string network in a contracting universe, together with the gravitational radiation background it has generated, can significantly affect the dynamics of the universe both locally and globally. The network can be an important source of radiation, entropy and inhomogeneity. We discuss the possible implications of these findings for bouncing and cyclic cosmological models.Comment: 11 RevTeX 4 pages, 6 figures; version to appear in Phys. Rev.

Aspects of String-Gas Cosmology at Finite Temperature

We study string-gas cosmology in dilaton gravity, inspired by the fact that it naturally arises in a string theory context. Our main interest is the thermodynamical treatment of the string-gas and the resulting implications for the cosmology. Within an adiabatic approximation, thermodynamical equilibrium and a small, toroidal universe as initial conditions, we numerically solve the corresponding equations of motions in two different regimes describing the string-gas thermodynamics: (i) the Hagedorn regime, with a single scale factor, and (ii) an almost-radiation dominated regime, which includes the leading corrections due to the lightest Kaluza Klein and winding modes, with two scale factors. The scale factor in the Hagedorn regime exhibits very slow time evolution with nearly constant energy and negligible pressure. By contrast, in case (ii) we find interesting cosmological solutions where the large dimensions continue to expand and the small ones are kept undetectably small.Comment: 21 pages, 5 eps figure

Oxidised cosmic acceleration

We give detailed proofs of several new no-go theorems for constructing flat four-dimensional accelerating universes from warped dimensional reduction. These new theorems improve upon previous ones by weakening the energy conditions, by including time-dependent compactifications, and by treating accelerated expansion that is not precisely de Sitter. We show that de Sitter expansion violates the higher-dimensional null energy condition (NEC) if the compactification manifold M is one-dimensional, if its intrinsic Ricci scalar R vanishes everywhere, or if R and the warp function satisfy a simple limit condition. If expansion is not de Sitter, we establish threshold equation-of-state parameters w below which accelerated expansion must be transient. Below the threshold w there are bounds on the number of e-foldings of expansion. If M is one-dimensional or R everywhere vanishing, exceeding the bound implies the NEC is violated. If R does not vanish everywhere on M, exceeding the bound implies the strong energy condition (SEC) is violated. Observationally, the w thresholds indicate that experiments with finite resolution in w can cleanly discriminate between different models which satisfy or violate the relevant energy conditions.Comment: v2: corrections, references adde

Testing "microscopic" theories of glass-forming liquids

We assess the validity of "microscopic" approaches of glass-forming liquids based on the sole k nowledge of the static pair density correlations. To do so we apply them to a benchmark provided by two liquid models that share very similar static pair density correlation functions while disp laying distinct temperature evolutions of their relaxation times. We find that the approaches are unsuccessful in describing the difference in the dynamical behavior of the two models. Our study is not exhausti ve, and we have not tested the effect of adding corrections by including for instance three-body density correlations. Yet, our results appear strong enough to challenge the claim that the slowd own of relaxation in glass-forming liquids, for which it is well established that the changes of the static structure factor with temperature are small, can be explained by "microscopic" appr oaches only requiring the static pair density correlations as nontrivial input.Comment: 10 pages, 7 figs; Accepted to EPJE Special Issue on The Physics of Glasses. Arxiv version contains an addendum to the appendix which does not appear in published versio

High-dose carfilzomib achieves superior anti-tumor activity over lowdose and recaptures response in relapsed/refractory multiple myeloma resistant to low-dose carfilzomib by co-inhibiting the β2 and β1 subunits of the proteasome complex

The optimal carfilzomib dosing is a matter of debate. We analyzed the inhibition profiles of proteolytic proteasome subunits β5, β2 and β1 after low-dose (20/27 mg/m2) versus high-dose (≥36 mg/m2) carfilzomib in 103 pairs of peripheral blood mononuclear cells from patients with relapsed/refractory (RR) multiple myeloma (MM). β5 activity was inhibited (median inhibition >50%) in vivo by 20 mg/m2, whereas β2 and β1 were co-inhibited only by 36 and 56 mg/m2, respectively. Co-inhibition of β2 (P=0.0001) and β1 activity (P=0.0005) differed significantly between high-dose and low-dose carfilzomib. Subsequently, high-dose carfilzomib showed significantly more effective proteasome inhibition than low-dose drug in vivo (P=0.0003). We investigated the clinical data of 114 patients treated with carfilzomib combinations. High-dose carfilzomib demonstrated a higher overall response rate (P=0.03) and longer progression-free survival (PFS) (P=0.007) than low-dose carfilzomib. Therefore, we escalated the carfilzomib dose to ≥ 36 mg/m2 in 16 patients who progressed during low-dose carfilzomib-containing therapies. High-dose carfilzomib recaptured response (≥ partial remission) in 9 (56%) patients with a median PFS of 4.4 months. Altogether, we provide the first in vivo evidence in RRMM patients that the molecular activity of high-dose carfilzomib differs from that of low-dose carfilzomib by co-inhibition of β2 and β1 proteasome subunits and, consequently, high-dose carfilzomib achieves a superior anti-MM effect than low-dose and recaptures response in RRMM being resistant to low-dose carfilzomib. The optimal carfilzomib dose should be ≥ 36 mg/m2 to reach a sufficient anti-tumor activity, while the balance between efficacy and tolerability should be considered in each patient.Bio-organic Synthesi