Base composition of intact nucleic acid oligomers

Base composition of intact nucleic acid oligomer

Repetitions in the polypeptide sequence of cytochromes

Protein evolution from peptides, gene duplications and deletions in polypeptides and cytochrome

Cyclic Universe and Infinite Past

We address two questions about the past for infinitely cyclic cosmology. The first is whether it can contain an infinite length null geodesic into the past in view of the Borde-Guth-Vilenkin (BGV) "no-go" theorem, The second is whether, given that a small fraction of spawned universes fail to cycle, there is an adequate probability for a successful universe after an infinite time. We give positive answers to both questions then show that in infinite cyclicity the total number of universes has been infinite for an arbitrarily long time.Comment: 7 pages. Clarification in discussion of infinite pas

Analysis of Accordion DNA Stretching Revealed by The Gold Cluster Ruler

A promising new method for measuring intramolecular distances in solution uses small-angle X-ray scattering interference between gold nanocrystal labels (Mathew-Fenn et al, Science, 322, 446 (2008)). When applied to double stranded DNA, it revealed that the DNA length fluctuations are strikingly strong and correlated over at least 80 base pair steps. In other words, the DNA behaves as accordion bellows, with distant fragments stretching and shrinking concertedly. This hypothesis, however, disagrees with earlier experimental and computational observations. This Letter shows that the discrepancy can be rationalized by taking into account the cluster exclusion volume and assuming a moderate long-range repulsion between them. The long-range interaction can originate from an ion exclusion effect and cluster polarization in close proximity to the DNA surface.Comment: 9 pages, 4 figures, to appear in Phys. Rev.

Size, shape, and flexibility of RNA structures

Determination of sizes and flexibilities of RNA molecules is important in understanding the nature of packing in folded structures and in elucidating interactions between RNA and DNA or proteins. Using the coordinates of the structures of RNA in the Protein Data Bank we find that the size of the folded RNA structures, measured using the radius of gyration, $R_G$, follows the Flory scaling law, namely, $R_G =5.5 N^{1/3}$ \AA where N is the number of nucleotides. The shape of RNA molecules is characterized by the asphericity $\Delta$ and the shape $S$ parameters that are computed using the eigenvalues of the moment of inertia tensor. From the distribution of $\Delta$, we find that a large fraction of folded RNA structures are aspherical and the distribution of $S$ values shows that RNA molecules are prolate ($S>0$). The flexibility of folded structures is characterized by the persistence length $l_p$. By fitting the distance distribution function $P(r)$ to the worm-like chain model we extracted the persistence length $l_p$. We find that $l_p\approx 1.5 N^{0.33}$ \AA. The dependence of $l_p$ on $N$ implies the average length of helices should increases as the size of RNA grows. We also analyze packing in the structures of ribosomes (30S, 50S, and 70S) in terms of $R_G$, $\Delta$, $S$, and $l_p$. The 70S and the 50S subunits are more spherical compared to most RNA molecules. The globularity in 50S is due to the presence of an unusually large number (compared to 30S subunit) of small helices that are stitched together by bulges and loops. Comparison of the shapes of the intact 70S ribosome and the constituent particles suggests that folding of the individual molecules might occur prior to assembly.Comment: 28 pages, 8 figures, J. Chem. Phys. in pres

Midwinter suppression of baroclinic storm activity on Mars: observations and models

Baroclinic instability and intense traveling wave activity on Mars is well known to occur in “storm zones” (Hollingsworth et al. 1996) close to the edge of the advancing or retreating polar ice cap. Such activity usually sets in during Martian fall and continues until the onset of the summer season when large-scale instability mostly ceases as the atmosphere is no longer baroclinically unstable. The stormy season is typically characterized by large-scale, zonally-propagating waves with zonal wavenumbers m = 1-3, the lower wavenumber modes typically penetrating to considerable altitude though may also be surface-intensified. As we show below, however, some observations suggest that this eddy activity does not persist uniformly throughout the autumn, winter and spring seasons, but appears to die down quite consistently within 10 sols or so either side of the winter solstice. This midwinter ‘solsticial pause’ appears to be a sufficiently consistent feature of each winter season in both hemispheres to be regarded as a significant feature of Martian climatology, and could affect a variety of aspects of Martian meteorology including global heat and momentum transport, occurrence of dust storms etc. A somewhat similar phenomenon has also been documented for the Earth (e.g. Nakamura 1992; Penny et al. 2010), especially in relation to seasonal variations in the north Pacific storm tracks. The cause of this phenomenon is still not well established, though suggested mechanisms include the effects of enhanced barotropic shear (the so-called ‘barotropic governor’ (James & Gray 1986) and interactions with topography over central Asia. In this presentation we examine evidence for this phenomenon in the assimilated record of Martian climate from the Thermal Emission Spectrometer on board the Mars Global Surveyor mission (MGSTES), in conjunction with the UK version of the LMD-Oxford-OU-IAA Mars GCM (Forget et al. 1999; Montabone et al. 2006; Lewis et al. 2007). This is further corroborated in other evidence from seasonal variations in the incidence of local and regional dust storms that owe their origin to circumpolar baroclinic storms. We also discuss the extent to which this ‘solsticial pause’ phenomenon is reproduced in stand-alone atmospheric models and present results of some simulations to test a number of hypotheses for its dynamical origin on Mars

Stretching of a single-stranded DNA: Evidence for structural transition

Recent experiments have shown that the force-extension (F-x) curve for single-stranded DNA (ssDNA) consisting only of adenine [poly(dA)] is significantly different from thymine [poly(dT)]. Here, we show that the base stacking interaction is not sufficient to describe the F-x curves as seen in the experiments. A reduction in the reaction co-ordinate arising from the formation of helix at low forces and an increase in the distance between consecutive phosphates of unstacked bases in the stretched state at high force in the proposed model, qualitatively reproduces the experimentally observed features. The multi-step plateau in the F-x curve is a signature of structural change in ssDNA.Comment: 10 pages, 4 figure

Cancer Cell Metabolism: One Hallmark, Many Faces

Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such changes within the metabolic program of a cancer cell can dictate by what means proliferative rewiring is driven, and can also impart heterogeneity in the metabolic dependencies of the cell. A better understanding of this heterogeneity may enable the development and optimization of therapeutic strategies that target tumor metabolism. Significance: Altered tumor metabolism is now a generally regarded hallmark of cancer. Nevertheless, the recognition of metabolic heterogeneity in cancer is becoming clearer as a result of advancements in several tools used to interrogate metabolic rewiring and dependencies. Deciphering this context-dependent heterogeneity will supplement our current understanding of tumor metabolism and may yield promising therapeutic and diagnostic utilities.National Institutes of Health (U.S.) (Grant CA129105

Structural, mechanical and thermodynamic properties of a coarse-grained DNA model

We explore in detail the structural, mechanical and thermodynamic properties of a coarse-grained model of DNA similar to that introduced in Thomas E. Ouldridge, Ard A. Louis, Jonathan P.K. Doye, Phys. Rev. Lett. 104 178101 (2010). Effective interactions are used to represent chain connectivity, excluded volume, base stacking and hydrogen bonding, naturally reproducing a range of DNA behaviour. We quantify the relation to experiment of the thermodynamics of single-stranded stacking, duplex hybridization and hairpin formation, as well as structural properties such as the persistence length of single strands and duplexes, and the torsional and stretching stiffness of double helices. We also explore the model's representation of more complex motifs involving dangling ends, bulged bases and internal loops, and the effect of stacking and fraying on the thermodynamics of the duplex formation transition.Comment: 25 pages, 16 figure

Perturbative Solutions of the Extended Constraint Equations in General Relativity

The extended constraint equations arise as a special case of the conformal constraint equations that are satisfied by an initial data hypersurface $Z$ in an asymptotically simple spacetime satisfying the vacuum conformal Einstein equations developed by H. Friedrich. The extended constraint equations consist of a quasi-linear system of partial differential equations for the induced metric, the second fundamental form and two other tensorial quantities defined on $Z$, and are equivalent to the usual constraint equations that $Z$ satisfies as a spacelike hypersurface in a spacetime satisfying Einstein's vacuum equation. This article develops a method for finding perturbative, asymptotically flat solutions of the extended constraint equations in a neighbourhood of the flat solution on Euclidean space. This method is fundamentally different from the `classical' method of Lichnerowicz and York that is used to solve the usual constraint equations.Comment: This third and final version has been accepted for publication in Communications in Mathematical Physic