The Importance of DNA Repair in Tumor Suppression

The transition from a normal to cancerous cell requires a number of highly specific mutations that affect cell cycle regulation, apoptosis, differentiation, and many other cell functions. One hallmark of cancerous genomes is genomic instability, with mutation rates far greater than those of normal cells. In microsatellite instability (MIN tumors), these are often caused by damage to mismatch repair genes, allowing further mutation of the genome and tumor progression. These mutation rates may lie near the error catastrophe found in the quasispecies model of adaptive RNA genomes, suggesting that further increasing mutation rates will destroy cancerous genomes. However, recent results have demonstrated that DNA genomes exhibit an error threshold at mutation rates far lower than their conservative counterparts. Furthermore, while the maximum viable mutation rate in conservative systems increases indefinitely with increasing master sequence fitness, the semiconservative threshold plateaus at a relatively low value. This implies a paradox, wherein inaccessible mutation rates are found in viable tumor cells. In this paper, we address this paradox, demonstrating an isomorphism between the conservatively replicating (RNA) quasispecies model and the semiconservative (DNA) model with post-methylation DNA repair mechanisms impaired. Thus, as DNA repair becomes inactivated, the maximum viable mutation rate increases smoothly to that of a conservatively replicating system on a transformed landscape, with an upper bound that is dependent on replication rates. We postulate that inactivation of post-methylation repair mechanisms are fundamental to the progression of a tumor cell and hence these mechanisms act as a method for prevention and destruction of cancerous genomes.Comment: 7 pages, 5 figures; Approximation replaced with exact calculation; Minor error corrected; Minor changes to model syste

Ecology of active and passive players and their impact on information selection

Is visitors' attendance a fair indicator of a web site's quality? Internet sub-domains are usually characterized by power law distributions of visits, thus suggesting a richer-get-richer process. If this is the case, the number of visits is not a relevant measure of quality. If, on the other hand, there are active players, i.e. visitors who can tell the value of the information available, better sites start getting richer after a crossover time.Comment: Accepted for publication on Phisica

Bogomol'nyi Equations of Maxwell-Chern-Simons vortices from a generalized Abelian Higgs Model

We consider a generalization of the abelian Higgs model with a Chern-Simons term by modifying two terms of the usual Lagrangian. We multiply a dielectric function with the Maxwell kinetic energy term and incorporate nonminimal interaction by considering generalized covariant derivative. We show that for a particular choice of the dielectric function this model admits both topological as well as nontopological charged vortices satisfying Bogomol'nyi bound for which the magnetic flux, charge and angular momentum are not quantized. However the energy for the topolgical vortices is quantized and in each sector these topological vortex solutions are infinitely degenerate. In the nonrelativistic limit, this model admits static self-dual soliton solutions with nonzero finite energy configuration. For the whole class of dielectric function for which the nontopological vortices exists in the relativistic theory, the charge density satisfies the same Liouville equation in the nonrelativistic limit.Comment: 30 pages(4 figures not included), RevTeX, IP/BBSR/93-6

Vortex solutions of a Maxwell-Chern-Simons field coupled to four-fermion theory

We find the static vortex solutions of the model of Maxwell-Chern-Simons gauge field coupled to a (2+1)-dimensional four-fermion theory. Especially, we introduce two matter currents coupled to the gauge field minimally: the electromagnetic current and a topological current associated with the electromagnetic current. Unlike other Chern-Simons solitons the N-soliton solution of this theory has binding energy and the stability of the solutions is maintained by the charge conservation laws.Comment: 7 pages, harvmac, To be published in Phys. Rev. D5

Magnetic Properties of a Bose-Einstein Condensate

Three hyperfine states of Bose-condensed sodium atoms, recently optically trapped, can be described as a spin-1 Bose gas. We study the behaviour of this system in a magnetic field, and construct the phase diagram, where the temperature of the Bose condensation $T_{BEC}$ increases with magnetic field. In particular the system is ferromagnetic below $T_{BEC}$ and the magnetization is proportional to the condensate fraction in a vanishing magnetic field. Second derivatives of the magnetisation with regard to temperature or magnetic field are discontinuous along the phase boundary.Comment: 5 pages, 5 figures included, to appear in Phys. Rev.

Distribution of the area enclosed by a 2D random walk in a disordered medium

The asymptotic probability distribution for a Brownian particle wandering in a 2D plane with random traps to enclose the algebraic area A by time t is calculated using the instanton technique.Comment: 4 pages, ReVTeX. Phys. Rev. E (March 1999), to be publishe

Consistency Conditions for Fundamentally Discrete Theories

The dynamics of physical theories is usually described by differential equations. Difference equations then appear mainly as an approximation which can be used for a numerical analysis. As such, they have to fulfill certain conditions to ensure that the numerical solutions can reliably be used as approximations to solutions of the differential equation. There are, however, also systems where a difference equation is deemed to be fundamental, mainly in the context of quantum gravity. Since difference equations in general are harder to solve analytically than differential equations, it can be helpful to introduce an approximating differential equation as a continuum approximation. In this paper implications of this change in view point are analyzed to derive the conditions that the difference equation should satisfy. The difference equation in such a situation cannot be chosen freely but must be derived from a fundamental theory. Thus, the conditions for a discrete formulation can be translated into conditions for acceptable quantizations. In the main example, loop quantum cosmology, we show that the conditions are restrictive and serve as a selection criterion among possible quantization choices.Comment: 33 page

In-medium Yang-Mills equations: a derivation and canonical quantization

The equations for Yang-Mills field in a medium are derived in a linear approximation with respect to the gauge coupling parameter and the external field. The obtained equations closely resemble the macroscopic Maxwell equations. A canonical quantization is performed for a family of Fermi-like gauges in the case of constant and diagonal (in the group indices) tensors of electric permittivity and magnetic permeability. The physical subspace is defined and the gauge field propagator is evaluated for a particular choice of the gauge. The propagator is applied for evaluation of the cross-section of ellastic quark scattering in the Born approximation. Possible applications to Cherenkov-type gluon radiation are commented briefly.Comment: 27 pages, references added, version extended with emphasis on non-Abelian gauge group impact on medium characteristics. To appear in J. Phys.

Synergistic interactions between XPC and p53 mutations in double-mutant mice: neural tube abnormalities and accelerated UV radiation-induced skin cancer

AbstractThe significance of DNA repair to human health has been well documented by studies on xeroderma pigmentosum (XP) patients, who suffer a dramatically increased risk of cancer in sun-exposed areas of their skin [1,2]. This autosomal recessive disorder has been directly associated with a defect in nucleotide excision–repair (NER) [1,2]. Like human XP individuals, mice carrying homozygous mutations in XP genes manifest a predisposition to skin carcinogenesis following exposure to ultraviolet (UV) radiation [3–5]. Recent studies have suggested that, in addition to roles in apoptosis [6] and cell-cycle checkpoint control [7] in response to DNA damage, p53 protein may modulate NER [8]. Mutations in the p53 gene have been observed in 50% of all human tumors [9] and have been implicated in both the early [10] and late [11] stages of skin cancer. To examine the consequences of a combined deficiency of the XPC and the p53 proteins in mice, we generated double-mutant animals. We document a spectrum of neural tube defects in XPC p53 mutant embryos. Additionally, we show that, following exposure to UV-B radiation, XPC p53 mutant mice have more severe solar keratosis and suffer accelerated skin cancer compared with XPC mutant mice that are wild-type with respect to p53

Oscillons: Resonant Configurations During Bubble Collapse

Oscillons are localized, non-singular, time-dependent, spherically-symmetric solutions of nonlinear scalar field theories which, although unstable, are extremely long-lived. We show that they naturally appear during the collapse of subcritical bubbles in models with symmetric and asymmetric double-well potentials. By a combination of analytical and numerical work we explain several of their properties, including the conditions for their existence, their longevity, and their final demise. We discuss several contexts in which we expect oscillons to be relevant. In particular, their nucleation during cosmological phase transitions may have wide-ranging consequences.Comment: 31 pages Revtex, 20 uufiles-encoded figures. Section "Possible Applications of Oscillons" slightly expande