61,225 research outputs found
A Computational Approach to Estimating Nondisjunction Frequency in Saccharomyces cerevisiae.
Errors segregating homologous chromosomes during meiosis result in aneuploid gametes and are the largest contributing factor to birth defects and spontaneous abortions in humans. Saccharomyces cerevisiae has long served as a model organism for studying the gene network supporting normal chromosome segregation. Measuring homolog nondisjunction frequencies is laborious, and involves dissecting thousands of tetrads to detect missegregation of individually marked chromosomes. Here we describe a computational method (TetFit) to estimate the relative contributions of meiosis I nondisjunction and random-spore death to spore inviability in wild type and mutant strains. These values are based on finding the best-fit distribution of 4, 3, 2, 1, and 0 viable-spore tetrads to an observed distribution. Using TetFit, we found that meiosis I nondisjunction is an intrinsic component of spore inviability in wild-type strains. We show proof-of-principle that the calculated average meiosis I nondisjunction frequency determined by TetFit closely matches empirically determined values in mutant strains. Using these published data sets, TetFit uncovered two classes of mutants: Class A mutants skew toward increased nondisjunction death, and include those with known defects in establishing pairing, recombination, and/or synapsis of homologous chromosomes. Class B mutants skew toward random spore death, and include those with defects in sister-chromatid cohesion and centromere function. Epistasis analysis using TetFit is facilitated by the low numbers of tetrads (as few as 200) required to compare the contributions to spore death in different mutant backgrounds. TetFit analysis does not require any special strain construction, and can be applied to previously observed tetrad distributions
Hydrogeochemistry of the Caribou-Poker Creeks Research Watershed
Bedrock of the Caribou-Poker Creeks Research Watershed dissolves incongruently
with a first-order rate constant of about 5 x 10-6 day-1 at 5° C. The
resulting solution is potassium-calcium-magnesium rich. The soil-plant environment
acts on this solution through sorption of potassium and by evapotranspiration
to yield a solution that is relatively depleted in potassium and
enriched in calcium and magnesium, but with the same molar ratio of Ca:Mg as
the fluid from the rock dissolution. This fluid from the soil-plant reservoir
is the dominant contributor of ions to stream waters.
Using the discriminant functions obtained by multiple discriminant
analysis
DPKR = 0.572Si02 + 0.240Ca + 2.89Mg - 0.384Na + 0.452N03 - 9.18
DCRB = 0.913Si02 + 0.042Ca + 1.28Mg + 1.17Na + 4.63N03 - 7.27,
the waters of Caribou Creek and Poker Creek can be distinguished on the basis
of chemical composition. In general, Poker Creek waters are slightly more
concentrated than Caribou Creek waters.
On the average, 1.4 x 10^13g H20/year leaves the watershed as surface
water. At an average calcium concentration of 14 ppm for the water, 0.1% for
the bedrock, and a watershed area of 46 mi^2, this flow corresponds to a maximum
loss of about 17 metric tons of rock per hectare per year
Rapid Determination of Multiple Reaction Pathways in Molecular Systems: The Soft-Ratcheting Algorithm
We discuss the ``soft-ratcheting'' algorithm which generates targeted
stochastic trajectories in molecular systems with scores corresponding to their
probabilities. The procedure, which requires no initial pathway guess, is
capable of rapidly determining multiple pathways between known states.
Monotonic progress toward the target state is not required. The soft-ratcheting
algorithm is applied to an all-atom model of alanine dipeptide, whose unbiased
trajectories are assumed to follow overdamped Langevin dynamics. All possible
pathways on the two-dimensional dihedral surface are determined. The associated
probability scores, though not optimally distributed at present, may provide a
mechanism for estimating reaction rates
Data types
A Mathematical
interpretation is given to the notion of a data type.
The main novelty is in the generality of the mathematical treatment
which allows procedural data types and circularly defined data types.
What is meant by data type is pretty close to what any computer
scientist would understand by this term or by data structure, type,
mode, cluster, class. The mathematical treatment is the conjunction
of the ideas of D. Scott on the solution of domain equations (Scott
(71), (72) and (76)) and the initiality property noticed by the
ADJ group (ADJ (75), ADJ (77)). The present work adds operations
to the data types proposed by Scott and generalizes the data types
of ADJ to procedural types and arbitrary circular type definitions.
The advantages of a mathematical interpretation of data types are
those of mathematical semantics in general : throwing light on some
ill-understood constructs in high-level programming languages, easing
the task of writing correct programs and making possible proofs of
correctness for programs or implementations"
Cougar Dispersal and Natal Homing in a Desert Environment
We present a review of cougar dispersal literature and the first evidence of natural (i.e., unmanipulated) homing behavior by a dispersing male cougar (Puma concolor) that sustained severe injuries crossing the northern Mojave Desert. Based on Global Positioning System and ground tracking data, the male traveled a total distance of 981.1 km at 5.03 km/d, including 170.31 km from the Desert National Wildlife Refuge to the northwestern Grand Canyon, where he sustained severe injuries. The interkill interval increased from 7.1 ± 2.7 d while he was in his natal range to 17.5 ± 4.9 d during dispersal. While homing, the male appeared to consume only reptiles until he died, 33.7 km from his capture site. In desert environments where prey availability is low, homing behavior may be an important strategy for dispersing cougars, providing a mechanism for persistence when the best quality habitats they encounter are already occupied by adult residents. Therefore, managing for habitat connectivity can ensure successful homing as well as dispersal on a greater scale than has been previously suggested. Elucidating the mechanisms that trigger homing during dispersal may provide critical insight into animal movements often overlooked as mundane behavior
Extending fragment-based free energy calculations with library Monte Carlo simulation: Annealing in interaction space
Pre-calculated libraries of molecular fragment configurations have previously
been used as a basis for both equilibrium sampling (via "library-based Monte
Carlo") and for obtaining absolute free energies using a polymer-growth
formalism. Here, we combine the two approaches to extend the size of systems
for which free energies can be calculated. We study a series of all-atom
poly-alanine systems in a simple dielectric "solvent" and find that precise
free energies can be obtained rapidly. For instance, for 12 residues, less than
an hour of single-processor is required. The combined approach is formally
equivalent to the "annealed importance sampling" algorithm; instead of
annealing by decreasing temperature, however, interactions among fragments are
gradually added as the molecule is "grown." We discuss implications for future
binding affinity calculations in which a ligand is grown into a binding site
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