Intrauterine programming of ageing

Ageing is an unavoidable corollary to being alive; the most intuitive interpretation of ageing being that it is the consequence of progressive body degeneration. In agreement with this, current models propose that ageing occurs through a stepwise accumulation of DNA damage, which ultimately limits the regenerative capacity of tissues. On the other hand, there is increasing evidence that fetal distress can influence the development of disease in adult life, a phenomenon known as ‘intrauterine programming’. The extent to which an intrauterine exposure to DNA damage can compromise lifespan remains unclear. My group has recently generated a murine model of a human syndrome linked to defective DNA repair and observed that these animals age prematurely, but the accumulation of DNA damage is restricted mostly to the embryonic period. Here, I discuss the implications of this finding and propose that ageing can be influenced by fetal distress.     

Multiple protein sequence alignment from tertiary structure comparison: assignment of global and residue confidence levels.

An algorithm is presented for the accurate and rapid generation of multiple protein sequence alignments from tertiary structure comparisons. A preliminary multiple sequence alignment is performed using sequence information, which then determines an initial superposition of the structures. A structure comparison algorithm is applied to all pairs of proteins in the superimposed set and a similarity tree calculated. Multiple sequence alignments are then generated by following the tree from the branches to the root. At each branchpoint of the tree, a structure-based sequence alignment and coordinate transformations are output, with the multiple alignment of all structures output at the root. The algorithm encoded in STAMP (STructural Alignment of Multiple Proteins) is shown to give alignments in good agreement with published structural accounts within the dehydrogenase fold domains, globins, and serine proteinases. In order to reduce the need for visual verification, two similarity indices are introduced to determine the quality of each generated structural alignment. Sc quantifies the global structural similarity between pairs or groups of proteins, whereas Pij' provides a normalized measure of the confidence in the alignment of each residue. STAMP alignments have the quality of each alignment characterized by Sc and Pij' values and thus provide a reproducible resource for studies of residue conservation within structural motifs.     

Lifetime reproductive success in reproductively suppressed female voles

A population of the grey red-backed vole, Clethrionomys rufocanus bedfordiae, was investigated on a 1 ha control grid and a 1 ha grid on which the voles were fed within a 2.1 ha outdoor enclosure in Hokkaido, Japan by live trapping from 1984 to 1986, for testing the Reproductive Suppression Model of Wasser and Barash (1983)-females can optimize their lifetime reproductive success by suppressing reproduction when future conditions for the survival of offspring are likely to be sufficiently better than present ones as to exceed the costs of the suppression itself. Age at the first pregnancy more varied in a higher density population on the experimental grid and females could be classified into the early and the late reproductive type in two generations (A: females born from February to June 1985; B: females born from September to November 1985). Lifetime reproductive success (the number of pregnancies, the number of successful litters, and the number of offspring) was not different between the early and the late reproducing females. The late reproducing females lived for longer periods than the early reproducing females, so that the loss by delayed start of reproduction was compensated for by a longer life span. Life span was not different between offspring of the early and the late reproducing females. These facts supported the Reproductive Suppression Model.     

Evolutionary epistemology as an overlapping,interlevel theory

I examine the branch of evolutionary epistemology which tries to account for the character of cognitive mechanisms in animals and humans by extending the biological theory of evolution to the neurophysiological substrates of cognition. Like Plotkin, I construe this branch as a struggling science, and attempt to characterize the sort of theory one might expect to find this truly interdisciplinary endeavor, an endeavor which encompasses not only evolutionary biology, cognitive psychology, and developmental neuroscience, but also and especially, the computational modeling of artificial life programming; I suggest that extending Schaffner's notion of interlevel theories to include both horizontal and vertical levels of abstraction best fits the theories currently being developed in cognitive science. Finally, I support this claim with examples drawn from computational modeling data using the genetic algorithm.     

The Value of a hoard: not just energy

We present a stochastic dynamic programming model of the contributionof stored food to winter survival. Using the acorn woodpecker(Melanerpes formtcivorus) as a model organism, we demonstratethat a hoard of small energetic value can impart considerableimprovement in the probability of surviving the winter and soimprove fitness. With this model we hope to resolve Koenig andMumme's paradox, that acorn woodpeckers expend much time andeffort to create and maintain hoards of acorns which provideno more that 16% of their energetic needs over the period inwhich they are used. We further demonstrate that the contributionof hoarded acorns to survival depends on the variability inforaging outcome, independently of the energetic value of thehoard in absolute terms. We point out that the results applyin principle to all hoarding animals and suggest a number offurther elaborations of the model.     

Site fidelity in predictable and unpredictable habitats

Summary Site fidelity, the tendency to return to a previously occupied location, has been observed in numerous species belonging to at least three phyla. In this paper I develop a general model using dynamic programming to investigate conditions under which fidelity to a previously occupied territory will be advantageous. The results predict that site fidelity should be inversely related to heterogeneity in territory quality and the animal's lifespan and positively related to the cost of changing territories, age and probability of mortality in the habitat. The predictability of reproductive outcome (defined as the probability that next period's outcome will be the same as this period's outcome) also affects site fidelity. In predictable habitats, changing territories may be favoured after a bad previous outcome. In contrast, settlement should be independent of the previous outcome in unpredictable habitats. Individuals should also be site-faithful in unpredictable habitats, as long as the mean territory quality is equal among available territories. I also investigate the success of two potential decision rules (always stay and win-stay: lose-switch) relative to the optimal settlement strategy. The results show that these rules may perform as well as the optimal strategy under certain conditions. The always stay strategy does well in unpredictable habitats, when the mean quality within a territory is equal among territories. In contrast, the win-stay: lose-switch strategy performs best in predictable habitats.     

A dynamic nonlinear optimization study of Mountain Pima subsistence technology

A dynamic nonlinear optimization analysis of subsistence patterns of the Mountain Pima of Chihuahua, Mexico, included requirements for adequate amounts of calories, calcium, vitamin A, vitamin C, and balanced protein. Two methods of incorporating nonenergy nutritional needs into a time minimization program were compared. The first was a constraint model with sharp boundaries between adequacy and fatality. The second involved multiplying the total work time by a series of nutrient indexing factors. Each factor was calculated as a function of the ratio between the recommended and actual rates of intake for all months and nutrients considered. Oxalate composition of some resources and seasonal variation in resource availability were taken into account. Two sets of data were analyzed, one for a year of adequate rainfall, the other for a year of severe drought. The predictions of the indexing model agreed more closely with observed intake patterns than did the predictions of the constraint model.     

杭州湾六市土地生态环境的数量评价及其在国土规划上的意义

在系统调查分析和特尔斐测定的基础上,选取人口密度、耕地人口负荷量、土地工业经济密度、居民点、厂矿用地、>25°土地面积、单位森林蓄积占用土地、耕地非旱涝保收面积7项指标,应用分值权重累加、系统聚类分析和模糊综合评价3种方法对杭州湾6市土地生态环境作综合分析评价,结果可应用于国土规划实践,对探讨土地生态环境评价的理论与方法有参考价值。     

The influence of basic plan parameters on calculated small field output factors – A multicenter study

PurposeThe influence of basic plan parameters such as slice thickness, grid resolution, algorithm type and field size on calculated small field output factors (OFs) was evaluated in a multicentric study.Methods and materialsThree computational homogeneous water phantoms with slice thicknesses (ST) 1, 2 and 3 mm were shared among twenty-one centers to calculate OFs for 1x1, 2x2 and 3x3 cm² field sizes (FSs) (normalized to 10x10 cm² FS), with their own treatment planning system (TPS) and the energy clinically used for stereotactic body radiation therapy delivery. OFs were calculated for each combination of grid resolution (GR) (1, 2 and 3 mm) and ST and finally compared with the OFs measured for the TPS commissioning. A multivariate analysis was performed to test the effect of basic plan parameters on calculated OFs.ResultsA total of 509 data points were collected. Calculated OFs are slightly higher than measured ones. The multivariate analysis showed that Center, GR, algorithm type, and FS are predictive variables of the difference between calculated and measured OFs (p < 0.001). As FS decreases, the spread in the difference between calculated and measured OFs became larger when increasing the GR. Monte Carlo and Analytical Anisotropic Algorithms, presented a dependence on GR (p < 0.01), while Collapsed Cone Convolution and Acuros did not. The effect of the ST was found to be negligible.ConclusionsModern TPSs slightly overestimate the calculated small field OFs compared with measured ones. Grid resolution, algorithm, center number and field size influence the calculation of small field OFs.     

Generalized Verlet Algorithm for Efficient Molecular Dynamics Simulations with Long-range Interactions

For the purpose of molecular dynamics simulations of large biopolymers we have developed a new method to accelerate the calculation of long-range pair interactions (e.g. Coulomb interaction). The algorithm introduces distance classes to schedule updates of non-bonding interactions and to avoid unnecessary computations of interactions between particles which are far apart. To minimize the error caused by the updating schedule, the Verlet integration scheme has been modified. The results of the method are compared to those of other approximation schemes as well as to results obtained by numerical integration without approximation. For simulation of a protein with 12 637 atoms our approximation scheme yields a reduction of computer time by a factor of seven. The approximation suggested can be implemented on sequential as well as on parallel computers. We describe an implementation on a (Transputer-based) MIMD machine with a systolic ring architecture.