Number of adaptive steps to a local fitness peak

We consider a population of genotype sequences evolving on a rugged fitness landscape with many local fitness peaks. The population walks uphill until it encounters a local fitness maximum. We find that the statistical properties of the walk length depend on whether the underlying fitness distribution has a finite mean. If the mean is finite, all the walk length cumulants grow with the sequence length but approach a constant otherwise. Experimental implications of our analytical results are also discussed

Evolutionary dynamics on strongly correlated fitness landscapes

We study the evolutionary dynamics of a maladapted population of self-replicating sequences on strongly correlated fitness landscapes. Each sequence is assumed to be composed of blocks of equal length and its fitness is given by a linear combination of four independent block fitnesses. A mutation affects the fitness contribution of a single block leaving the other blocks unchanged and hence inducing correlations between the parent and mutant fitness. On such strongly correlated fitness landscapes, we calculate the dynamical properties like the number of jumps in the most populated sequence and the temporal distribution of the last jump which is shown to exhibit a inverse square dependence as in evolution on uncorrelated fitness landscapes. We also obtain exact results for the distribution of records and extremes for correlated random variables

Centrifugal terms in the WKB approximation and semiclassical quantization of hydrogen

A systematic semiclassical expansion of the hydrogen problem about the classical Kepler problem is shown to yield remarkably accurate results. Ad hoc changes of the centrifugal term, such as the standard Langer modification where the factor l(l+1) is replaced by (l+1/2)^2, are avoided. The semiclassical energy levels are shown to be exact to first order in $\hbar$ with all higher order contributions vanishing. The wave functions and dipole matrix elements are also discussed.Comment: 5 pages, to appear in Phys. Rev.

A probabilistic fusion framework for 3-D reconstruction using heterogeneous sensors

This letter proposes a framework to perform 3-D reconstruction using a heterogeneous sensor network, with potential use in augmented reality, human behavior understanding, smart-room implementations, robotics, and many other applications. We fuse orientation measurements from inertial sensors, images from cameras and depth data from Time of Flight sensors within a probabilistic framework in a synergistic manner to obtain robust reconstructions. A fully probabilistic method is proposed to efficiently fuse the multi-modal data of the system

MTA1 Interacts with MAT1, a cyclin-dependent kinase-activating kinase complex ring finger factor and regulates estrogen receptor transactivation functions

The transcriptional activity of estrogen receptor-α is controlled by coregulators. MTA1 (metastasis-associated protein1) represses estrogen receptor-α-driven transcription by recruiting Histone Deacetylases (HDACs) to the estrogen response element containing target gene chromatin in breast cancer cells. Using a yeast two-hybrid screen with the MTA1 C-terminal domain as bait, we identified MAT1 (menage a trois 1) as an MTA1-binding protein. MAT1 is an assembly/targeting factor for cyclin-dependent kinase-activating kinase (CAK), which has been shown to functionally interact with general transcriptional factor TFIIH, a known inducer of ER transactivation. We show that estrogen signaling promotes nuclear translocation of MAT1 and that MTA1 interacts with MAT1 both in vitro and in vivo. MAT1 binds to the C-terminal 389–441 amino acids GATA domain and N-terminal 1–164 amino acids bromo-domain of MTA1, whereas MTA1 binds to the N-terminal ring finger domain of the MAT1. In addition, MAT1 interacts with the activation function 2 domain of ER and colocalizes with ER in activated cells. MTA1 deregulation in breast cancer cells led to its interactions with the CAK complex components, ER and HDAC2. Accordingly, MTA1 inhibited CAK stimulation of ER transactivation that was partially relieved by HDAC inhibitor trichostatin A, suggesting that MTA1 might inhibit CAK-induced transactivation function of ER by recruiting HDAC. Furthermore, MTA1 overexpression inhibited the ability of CAK complex to phosphorylate ER. Together, these findings identified MAT1 as a target of MTA1 and provided new evidence to suggest that the transactivation functions of ER might be influenced by the regulatory interactions between CAK and MTA1 in breast cancer cells

Chemically induced solidification : a new way to produce thin solid-near- net shapes

In-situ observation of the solidification of high carbon steel (4 wt% C) through decarburization has been carried out as a feasibility study into reducing high power usage and high CO2 production involved in steel making. Decarburization has been carried out under both air and pure N2 atmospheres at temperature of 1573K (1300 °C) and 1673K (1400 °C). A solidified shell of around 500μm was formed with carbon concentrations reduced down to 1% in as short as 18s

On the catch trend of mechanised gill netters landed at Madras fisheries harbour

An average of about 7 drift gill nets and 3 seasonally operating bottom set gill nets land at the Madras Fisheries Harbour by the Pablo type mechanised boats. These mechanised boats in the length range of 7 - 8 m are fitted with 24 – 30 Hp engines and operate in area off Madras coast in 20 - 50 m depth range throughout the year except the southeast monsoon period, October- December. The catch trend of the gill netters with special reference to the seasonal abundance of the different groups caught during the period, 1988 - '89 are dealt with in the present study

Comparing Chemistry to Outcome: The Development of a Chemical Distance Metric, Coupled with Clustering and Hierarchal Visualization Applied to Macromolecular Crystallography

Many bioscience fields employ high-throughput methods to screen multiple biochemical conditions. The analysis of these becomes tedious without a degree of automation. Crystallization, a rate limiting step in biological X-ray crystallography, is one of these fields. Screening of multiple potential crystallization conditions (cocktails) is the most effective method of probing a proteins phase diagram and guiding crystallization but the interpretation of results can be time-consuming. To aid this empirical approach a cocktail distance coefficient was developed to quantitatively compare macromolecule crystallization conditions and outcome. These coefficients were evaluated against an existing similarity metric developed for crystallization, the C6 metric, using both virtual crystallization screens and by comparison of two related 1,536-cocktail high-throughput crystallization screens. Hierarchical clustering was employed to visualize one of these screens and the crystallization results from an exopolyphosphatase-related protein from Bacteroides fragilis, (BfR192) overlaid on this clustering. This demonstrated a strong correlation between certain chemically related clusters and crystal lead conditions. While this analysis was not used to guide the initial crystallization optimization, it led to the re-evaluation of unexplained peaks in the electron density map of the protein and to the insertion and correct placement of sodium, potassium and phosphate atoms in the structure. With these in place, the resulting structure of the putative active site demonstrated features consistent with active sites of other phosphatases which are involved in binding the phosphoryl moieties of nucleotide triphosphates. The new distance coefficient, CDcoeff, appears to be robust in this application, and coupled with hierarchical clustering and the overlay of crystallization outcome, reveals information of biological relevance. While tested with a single example the potential applications related to crystallography appear promising and the distance coefficient, clustering, and hierarchal visualization of results undoubtedly have applications in wider fields

Semiclassical energy formulas for power-law and log potentials in quantum mechanics

We study a single particle which obeys non-relativistic quantum mechanics in R^N and has Hamiltonian H = -Delta + V(r), where V(r) = sgn(q)r^q. If N \geq 2, then q > -2, and if N = 1, then q > -1. The discrete eigenvalues E_{n\ell} may be represented exactly by the semiclassical expression E_{n\ell}(q) = min_{r>0}\{P_{n\ell}(q)^2/r^2+ V(r)}. The case q = 0 corresponds to V(r) = ln(r). By writing one power as a smooth transformation of another, and using envelope theory, it has earlier been proved that the P_{n\ell}(q) functions are monotone increasing. Recent refinements to the comparison theorem of QM in which comparison potentials can cross over, allow us to prove for n = 1 that Q(q)=Z(q)P(q) is monotone increasing, even though the factor Z(q)=(1+q/N)^{1/q} is monotone decreasing. Thus P(q) cannot increase too slowly. This result yields some sharper estimates for power-potential eigenvlaues at the bottom of each angular-momentum subspace.Comment: 20 pages, 5 figure

The Roles of Transmembrane Domain Helix-III during Rhodopsin Photoactivation

Background: Rhodopsin, the prototypic member of G protein-coupled receptors (GPCRs), undergoes isomerization of 11- cis-retinal to all-trans-retinal upon photoactivation. Although the basic mechanism by which rhodopsin is activated is well understood, the roles of whole transmembrane (TM) helix-III during rhodopsin photoactivation in detail are not completely clear. Principal Findings: We herein use single-cysteine mutagenesis technique to investigate conformational changes in TM helices of rhodopsin upon photoactivation. Specifically, we study changes in accessibility and reactivity of cysteine residues introduced into the TM helix-III of rhodopsin. Twenty-eight single-cysteine mutants of rhodopsin (P107C-R135C) were prepared after substitution of all natural cysteine residues (C140/C167/C185/C222/C264/C316) by alanine. The cysteine mutants were expressed in COS-1 cells and rhodopsin was purified after regeneration with 11-cis-retinal. Cysteine accessibility in these mutants was monitored by reaction with 4, 49-dithiodipyridine (4-PDS) in the dark and after illumination. Most of the mutants except for T108C, G109C, E113C, I133C, and R135C showed no reaction in the dark. Wide variation in reactivity was observed among cysteines at different positions in the sequence 108–135 after photoactivation. In particular, cysteines at position 115, 119, 121, 129, 131, 132, and 135, facing 11-cis-retinal, reacted with 4-PDS faster than neighboring amino acids. The different reaction rates of mutants with 4-PDS after photoactivation suggest that the amino acids in different positions in helix-III are exposed to aqueous environment to varying degrees. Significance: Accessibility data indicate that an aqueous/hydrophobic boundary in helix-III is near G109 and I133. The lack of reactivity in the dark and the accessibility of cysteine after photoactivation indicate an increase of water/4-PDS accessibility for certain cysteine-mutants at Helix-III during formation of Meta II. We conclude that photoactivation resulted in water-accessible at the chromophore-facing residues of Helix-III.National Institutes of Health (U.S.) (grant GM28289)National Eye Institute (Grant Grant EY11716)National Science Foundation (U.S.) (grant EIA-0225609