43 research outputs found
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