1,801 research outputs found
Computational Investigation of the Interactions Between Bioactive Compounds and Biological Assemblies
Design of small molecules is an ongoing focus for developing agents against pathogenic viruses and bacteria that are threats to worldwide health. Viruses such as Zika feature assemblies of repeat peptide subunits or capsid proteins which are potential targets for antiviral compounds. Other protein assemblies are implicated in pathology of Alzheimer’s Disease (AD) and additional neurodegenerative diseases characterized by large assemblies of misfolded proteins such as amyloid-beta (Aβ) and tau. Recent studies on a class of conjugated polyelectrolytes (CPEs) with phenylene ethynylene moieties and charged functional groups have shown potential both as bioactive antimicrobials and theragnostic sensing agents for tracking Alzheimer’s based protein aggregates. A second type of small molecule, curcumin, is used as a therapeutic compound for a number of diseases including AD. Recent evidence shows that this molecule is able to interfere with fibril growth. In addition, curcumin attenuates Aβ-membrane interactions and Aβ toxicity. Our goal is to use computational techniques to better understand the interactions governing small molecule (including OPEs and curcumin) behavior when bound to capsid or fibrillar protein assemblies. We are focused on determining how and where these molecules bind in addition to comparing relative binding strength
Delayed Repair of Myelomeningoceles
Objective: Myelomeningocele is a defect that is typically surgically repaired within the first few days of life in developed countries to minimize the risk of meningitis. If left unrepaired, these children may survive to have their meningocele sac epithelialize. The surgical reduction and closure of an epithelialized myelomeningocele represents a unique challenge for the neurosurgeon, as it requires a modification of the typical closure technique.
Methods: 10 years experience in 97 patients with the delayed (\u3e6 months) repair of myelomeningoceles was the basis of this report. Results: Repair technique in a child with a myelomeningocele that was not repaired at birth presented a surgical challenge whose solutions are presented herein.
Conclusion: Delayed closure of myelomeningoceles is facilitated by adherence to lessons learned form surgical experience on medical missions to Guatemala
Exploring a string-like landscape
We explore inflationary trajectories within randomly-generated
two-dimensional potentials, considered as a toy model of the string landscape.
Both the background and perturbation equations are solved numerically, the
latter using the two-field formalism of Peterson and Tegmark which fully
incorporates the effect of isocurvature perturbations. Sufficient inflation is
a rare event, occurring for only roughly one in potentials. For models
generating sufficient inflation, we find that the majority of runs satisfy
current constraints from WMAP. The scalar spectral index is less than 1 in all
runs. The tensor-to-scalar ratio is below the current limit, while typically
large enough to be detected by next-generation CMB experiments and perhaps also
by Planck. In many cases the inflationary consistency equation is broken by the
effect of isocurvature modes.Comment: 24 pages with 8 figures incorporated, matches version accepted by
JCA
Multi-field Inflation with a Random Potential
Motivated by the possibility of inflation in the cosmic landscape, which may
be approximated by a complicated potential, we study the density perturbations
in multi-field inflation with a random potential. The random potential causes
the inflaton to undergo a Brownian motion with a drift in the D-dimensional
field space. To quantify such an effect, we employ a stochastic approach to
evaluate the two-point and three-point functions of primordial perturbations.
We find that in the weakly random scenario the resulting power spectrum
resembles that of the single field slow-roll case, with up to 2% more red tilt.
The strongly random scenario, leads to rich phenomenologies, such as primordial
fluctuations in the power spectrum on all angular scales. Such features may
already be hiding in the error bars of observed CMB TT (as well as TE and EE)
power spectrum and can be detected or falsified with more data coming in the
future. The tensor power spectrum itself is free of fluctuations and the tensor
to scalar ratio is enhanced. In addition a large negative running of the power
spectral index is possible. Non-Gaussianity is generically suppressed by the
growth of adiabatic perturbations on super-horizon scales, but can possibly be
enhanced by resonant effects or arise from the entropic perturbations during
the onset of (p)reheating. The formalism developed in this paper can be applied
to a wide class of multi-field inflation models including, e.g. the N-flation
scenario.Comment: More clarifications and references adde
Multi-field Inflation with a Random Potential
Motivated by the possibility of inflation in the cosmic landscape, which may
be approximated by a complicated potential, we study the density perturbations
in multi-field inflation with a random potential. The random potential causes
the inflaton to undergo a Brownian motion with a drift in the D-dimensional
field space. To quantify such an effect, we employ a stochastic approach to
evaluate the two-point and three-point functions of primordial perturbations.
We find that in the weakly random scenario the resulting power spectrum
resembles that of the single field slow-roll case, with up to 2% more red tilt.
The strongly random scenario, leads to rich phenomenologies, such as primordial
fluctuations in the power spectrum on all angular scales. Such features may
already be hiding in the error bars of observed CMB TT (as well as TE and EE)
power spectrum and can be detected or falsified with more data coming in the
future. The tensor power spectrum itself is free of fluctuations and the tensor
to scalar ratio is enhanced. In addition a large negative running of the power
spectral index is possible. Non-Gaussianity is generically suppressed by the
growth of adiabatic perturbations on super-horizon scales, but can possibly be
enhanced by resonant effects or arise from the entropic perturbations during
the onset of (p)reheating. The formalism developed in this paper can be applied
to a wide class of multi-field inflation models including, e.g. the N-flation
scenario.Comment: More clarifications and references adde
Novel colours and the content of experience
I propose a counterexample to naturalistic representational theories of phenomenal character. The counterexample is generated by experiences of novel colours reported by Crane and Piantanida. I consider various replies that a representationalist might make, including whether novel colours could be possible colours of objects and whether one can account for novel colours as one would account for binary colours or colour mixtures. I argue that none of these strategies is successful and therefore that one cannot fully explain the nature of the phenomenal character of perceptual experiences using a naturalistic conception of representation
Cosmology of the Tachyon in Brane Inflation
In certain implementations of the brane inflationary paradigm, the exit from
inflation occurs when the branes annihilate through tachyon condensation. We
investigate various cosmological effects produced by this tachyonic era. We
find that only a very small region of the parameter space (corresponding to
slow-roll with tiny inflaton mass) allows for the tachyon to contribute some
e-folds to inflation. In addition, non-adiabatic density perturbations are
generated at the end of inflation. When the brane is moving relativistically
this contribution can be of the same order as fluctuations produced 55 e-folds
before the end of inflation. The additional contribution is very nearly
scale-invariant and enhances the tensor/scalar ratio. Additional
non-gaussianities will also be generated, sharpening current constraints on
DBI-type models which already predict a significantly non-gaussian signal.Comment: 30 pages, 2 figures; v3, minor revision, JCAP versio
Is Brane Inflation Eternal?
In this paper, we show that eternal inflation of the random walk type is
generically absent in the brane inflationary scenario. Depending on how the
brane inflationary universe originated, eternal inflation of the false vacuum
type is still quite possible. Since the inflaton is the position of the
D3-brane relative to the anti-D3-brane inside the compactified bulk with finite
size, its value is bounded. In DBI inflation, the warped space also restricts
the amplitude of the scalar fluctuation. These upper bounds impose strong
constraints on the possibility of eternal inflation. We find that eternal
inflation due to the random walk of the inflaton field is absent in both the
KKLMMT slow roll scenario and the DBI scenario. A more careful analysis for the
slow-roll case is also presented using the Langevin equation, which gives very
similar results. We discuss possible ways to obtain eternal inflation of the
random walk type in brane inflation. In the multi-throat brane inflationary
scenario, the branes may be generated by quantum tunneling and roll out the
throat. Eternal inflation of the false vacuum type inevitably happens in this
scenario due to the tunneling process. Since these scenarios have different
cosmological predictions, more data from the cosmic microwave background
radiation will hopefully select the specific scenario our universe has gone
through.Comment: 32 pages; v2: references and comments adde
Cosmological Landscape From Nothing: Some Like It Hot
We suggest a novel picture of the quantum Universe -- its creation is
described by the {\em density matrix} defined by the Euclidean path integral.
This yields an ensemble of universes -- a cosmological landscape -- in a mixed
state which is shown to be dynamically more preferable than the pure quantum
state of the Hartle-Hawking type. The latter is dynamically suppressed by the
infinitely large positive action of its instanton, generated by the conformal
anomaly of quantum fields within the cosmological bootstrap (the
self-consistent back reaction of hot matter). This bootstrap suggests a
solution to the problem of boundedness of the on-shell cosmological action and
eliminates the infrared catastrophe of small cosmological constant in Euclidean
quantum gravity. The cosmological landscape turns out to be limited to a
bounded range of the cosmological constant . The domain is ruled out by the
back reaction effect which we analyze by solving effective Euclidean equations
of motion. The upper cutoff is enforced by the quantum effects of vacuum energy
and the conformal anomaly mediated by a special ghost-avoidance renormalization
of the effective action. They establish a new quantum scale
which is determined by the coefficient of the topological Gauss-Bonnet term in
the conformal anomaly. This scale is realized as the upper bound -- the
limiting point of an infinite sequence of garland-type instantons which
constitute the full cosmological landscape. The dependence of the cosmological
constant range on particle phenomenology suggests a possible dynamical
selection mechanism for the landscape of string vacua.Comment: Final version, to appear in JCA
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