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The Warrior Zero Body Weight Challenge

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The Warrior Zero Body Weight Challenge Summary


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Propensity Analysis of Fitness

Levins (1968) has remarked that ''fitness enters population biology as a vague heuristic notion, rich in metaphor but poor in precision.'' No doubt this is accurate as a characterization of the unclarity surrounding the role of fitness in evolutionary theory, even among biologists who use the term. But such unclarity is quite compatible with the fact that fitness plays an essential explanatory role in evolutionary theory. It is to the task of increasing the precision of the concept of fitness as well as making explicit this explanatory role that we now turn. We have already seen that fitness is somehow connected with success at survival and reproduction, although it cannot be defined in terms of actual survival and reproductive success. Why have evolutionary biologists continued to confuse fitness with actual descendant contribution We believe that the confusion involves a misidentification of the post facto survival and reproductive success of an organism with the ability of an...

Fitness2 Fitness of Types

Having defined fitness1, we are in a position to define the fitness2 of types. As will become apparent in what follows, it is the fitness of types which figures primarily in explanations of microevolutionary change. Intuitively, the fitness of a type (genotype of phenotype) reflects the contribution of a particular gene or trait to the expected descendant contribution (i.e., the fitness1) of possessors of the gene or trait. Differences in the contributions of alternate genes or traits would be easy to detect in populations of individuals which were phenotypically identical except in regard to the trait or gene in question. In reality, though, individuals differ with regard to many traits, so that the contribution of one or another trait to fitnessj is not so straightforward. In fact, the notion of any simple, absolute contribution is quite meaningless. For a trait acts in conjunction with many other traits in influencing the survival and reproductive success of its possessors. Thus,...

Inclusive Fitness Theory

Within the individualistic tradition in biology, natural selection is widely thought to maximize a property called inclusive fitness, which is the sum of an individual's effects on the fitness of others multiplied by the probability that the others will share the genes causing the behavior. As Hamilton (1963 354-355) originally put it In this formulation, individuals evolve to maximize the fitness of ''their genes'' relative to other genes in the population, regardless of whether ''their genes'' are located in children, siblings, cousins, parents, and so on. Aid-giving toward relatives therefore ceases to appear altruistic, and becomes part of an individual's ''selfish'' strategy to maximize its inclusive fitness. Even sterility and death can be inclusive fitness maximizing if the positive effects on relatives are sufficiently great. Let us pursue this idea by considering an Aa female who mates with an aa male and produces a clutch of ten offspring, five of whom are Aa and the other...

Saccharomyces cerevisiae

While such genome-wide descriptive studies are informative, the real advances in the yeast field have been in pioneering the technologies for directly assessing gene function. Within a few years of completion of the genome sequence, a panel of strains deleted for each of the approximately 6000 genes was developed. This allows for systematic, whole-genome 'reverse genetic' screening, wherein the identity of the gene mutated is known and the resulting phenotypes are assessed. By flanking each deletion with a molecular bar code consisting of a unique oligonucleotide sequence, the presence or absence of a particular deletion in a pool of strains can be detected by isolation of DNA and hybridization to microarrays consisting of oligonucleotides complementary to each bar code (Figure 2).40,41 When subjected to various environmental stresses in liquid culture, such as addition of a drug, individual yeast deletion strains within the pool exhibit differential fitness. During growth, strains...

Laws in the Evolutionary Process

My chapter ''Two Outbreaks of Lawlessness in Philosophy of Biology'' replies to Beatty's arguments and also to arguments for a similar conclusion advanced by Alexander Rosenberg in his 1994 book Instrumental Biology or the Disunity of Science. In reply to Beatty, I suggest that if a contingent evolutionary event E causes a biological generalization G to be true later on, then we should expect there to be a law linking E to G. This is consistent with Beatty's claim that if G is contingent on E (where E is contingent), then G is not a law. I also argue that the prevalence of relative significance controversies in evolutionary biology is no evidence for biology's lawlessness and that biology has not abandoned the principle of parsimony, when that principle is properly understood. Rosenberg's brief for lawlessness is based on the fact that biological properties are multiply realizable. Take a biological property like ''fitness'' or ''predator '' these predicates apply to organisms that...

Mills and John H Beatty

The concept of fitness is a notion of central importance to evolutionary theory. Yet the interpretation of this concept and its role in explanations of evolutionary phenomena have remained obscure. We provide a propensity interpretation of fitness, which we argue captures the intended reference of this term as it is used by evolutionary theorists. Using the propensity interpretation of fitness, we provide a Hempelian reconstruction of explanations of evolutionary phenomena, and we show why charges of circularity which have been levelled against explanations in evolutionary theory are mistaken. Finally, we provide a definition of natural selection which follows from the propensity interpretation of fitness, and which handles all the types of selection discussed by biologists, thus improving on extant definitions. whether it is worth bothering with them. But the fact is that there is a major problem in the foundations of evolutionary theory which remains unsolved, and which continues to...

The Charge of Circularity

According to the most frequently cited definitions of ''fitness,'' that term refers to the actual number of offspring left by an individual or type relative to the actual contribution of some reference individual or type. For instance, Waddington (1968, p. 19) sug gests that the fittest individuals are those which are ''most effective in leaving gametes to the next generation.'' According to Lerner (1958), ''the individuals who have more offspring are fitter in the Darwinian sense.'' Grant (1977, p. 66) construes fitness as ''a measure of reproductive success.'' And Crow and Kimura (1970, p. 5) regard fitness ''as a measure of both survival and reproduction'' (see also Dobzhansky 1970, pp. 101-102 Wilson 1975, p. 585 Mettler and Gregg 1969, p. 93). These definitions of ''fitness'' in terms of actual survival and reproductive success are straightforward and initially intuitively satisfying. However, such definitions lead to justifiable charges that certain explanations invoking fitness...

Common Exercise Related Injuries

Weight-bearing exercise such as jogging, running, or even brisk walking can place a lot of stress on joints and muscles. If you are overweight, you may be at greater risk for discomfort, pain, or injury from weight-bearing exercise early in your fitness program or when increasing your level of intensity or duration. Overuse injuries affect most men who exercise from time to time. There are a number of things you can do to prevent common exercise-related injuries such as sprains, strains, inflammation, and pain. Minor injuries usually can be treated with simple first-aid measures (see RICE routine, page 65). However, if you have a more serious injury, such as a broken bone, go directly to a hospital emergency department. Exercise and Fitness In general, the best way to prevent exercise-related injury is to start exercising slowly and increase your intensity gradually. Being overly zealous in your workouts, especially in the beginning, will quickly result in an injury that will put you...

Propensity Analysis of Natural Selection

One consequence of our propensity interpretation of fitness is that the analysis also points to an improved definition of ''natural selection.'' As was noted earlier, the concepts of fitness and natural selection are inextricably bound so much so that misinterpretations of fitness are reflected in misinterpretations of natural selection. Thus, according to one of the more popular interpretations of natural selection, that process occurs whenever two or more individuals leave different numbers of offspring, or whenever two or more types leave different average numbers of offspring. For example, Crow and Kimura (1970) stipulate that ''selection occurs when one genotype leaves a different number of progeny than another'' (p. 173). Insofar as it is correct to say that the fittest are selected, this definition of ''selection'' clearly reflects a definition of ''fitness'' in terms of actual descendant contribution. In each of these cases, selection is construed as involving more than just...

The Long Term and the Short Term

The definition of fitness as expected number of offspring has a one-generation time scale. Why think of fitness in this way rather than as having a longer time horizon Consider figure 2.1 adapted from Beatty and Finsen (1989). Trait A produces more offspring than trait B (in expectation) before time t* however, after t*, A produces fewer offspring than B, and in fact A eventually produces zero offspring. The puzzle is that A seems to be fitter than B in the short term, whereas B seems to be fitter than A in the long term. Which of these descriptions is correct The issue of whether fitness should be defined as a short-term or a long-term quantity will be familiar to biologists from the work of Thoday (1953, 1958), who argued that fitness should be defined as the probability of leaving descendants in the very long run he suggests 108 years as an appropriate time scale. Thoday (1958, p. 317) says that a long-term measure is needed to obtain a definition of evolutionary progress. This...

When a One Generation Time Frame Is Inadequate

The concept of short-term fitness discussed so far has a one-generation time frame an organism at the egg stage has a probability p of reaching reproductive age and, once it is an adult, it has e as its expected number of offspring the product pe is its overall fitness. However, a one-generation time frame will not always be satisfactory for the concept of short-term fitness. Fisher's (1930) model of sex ratio shows why (Sober 1984). If, in expectation, one female has 5 sons and 5 daughters whereas another produces 10 daughters and 0 sons, how can their different sex-ratio strategies make a difference in their fitnesses Fisher saw that the answer is invisible if we think one generation ahead but falls into place if we consider two. The sex ratio exhibited by a female's progeny influences how many grandoffspring she will have. Other examples may be constructed of the same type. Parental care is a familiar biological phenomenon, but let us consider its extension care of grandoffspring....

Socioecology and homology

A final criterion suggest that two behaviours are likely to be analogous if the biological role (or function) of those behaviours is similar, or if the two behaviours could have been subjected to similar selection pressures (e.g. Mayr, 1958). This definition is difficult to apply because it refers to selection in a broad way, stressing its significance but also highlighting the lack of available evidence concerning the nature of variation in behaviour, its genetic basis and its relation to fitness.

Valid Individualism and Cheap Individualism

There is, however, another way to calculate fitness in the two-group model that leads to another definition of individual selection. Instead of separately considering evolution within groups and the differential fitness of groups, we can directly average the fitness of A- and S-types across all groups. Thus, the 2 A-types in groups one have 9.96 offspring and the 8 A-types in group two have 12.99 offspring, for an average fitness of 0.2(9.96) +0.8(12.99) 12.38. The 8 S-types in group one have 11.01 offspring and the 2 S-types in group two have 14.04 offspring, for an average fitness of 0.8(11.01) +0.2(14.04) 11.62. The average A-type individual is more fit then the average S-type individual, which is merely another way of saying that it evolves. Let us now return to the individualistic claim that ''virtually all adaptations evolve by individual selection.'' If by individual selection we mean the fitness of individuals averaged across all groups, we have said nothing at all. Since this...

The Evolution of Avirulence in Parasites and Diseases

In many interactions the exploiter cannot evolve to be avirulent it profits a fox nothing to spare the hare. But if the fitness of an individual parasite or its offspring is lowered by the death of its host, avirulence is advantageous. The myxoma virus, introduced into Australia to control European rabbits, at first caused immense mortality. But within a few years mortality levels were lower, both because the rabbits had evolved resistance and because the virus had evolved to be less lethal. . . . Because the virus is transmitted by mosquitoes that feed only on living rabbits, virulent virus genotypes are less likely to spread than benign genotypes italics mine . Avirulence evolves not to assure a stable future supply of hosts, but to benefit individual parasites. Thus, by the simple procedure of comparing the fitness of virulent and avirulent types across all hosts (see italicized portion of text), rather than within single hosts, the evolution of avirulence can be made to appear an...

Diploid Population Genetics and Evolutionary Game Theory

My final example involves a comparison between two seemingly different bodies of theory in evolutionary biology. Diploid population genetics models begin with a population of gametic types (A, a) which combine into pairs to form diploid genotypes (AA, Aa, aa). Selection usually is assumed to occur in the diploid stage, after which the genotypes dissociate back into gametes and the process is reiterated. The most common way for selection to occur in these models is for some genotypes to survive and reproduce better than others, the standard process of between-individual selection. In addition, however, it is possible for some alleles to survive and reproduce better than others within single individuals. For example, the rules of meiosis usually cause the two chromosome sets to be equally represented in the gametes. Some alleles manage to break the rules of meiosis, however, biasing their own transmission into the sperm and eggs of heterozygotes. The differential fitness of alleles...

Parallel Argument for the Human Sciences

As with any theory of human behavior, the first step is to specify the rules that cause people to choose among alternative behaviors, which serve as the analog of natural selection in an evolutionary model. Following Axelrod and others (Axelrod and Hamilton 1981 Brown et al. 1982 Pollock 1988), assume that humans adopt behaviors that maximize a given utility, relative to competing behaviors in the population. The utility might be pleasure (to a psychologist), annual income (to an economist), or genetic fitness (to a sociobiologist). The details of the utility are relatively unimportant because the hallmark of a hierarchical model is not the nature of the utility but the way it is partitioned into within- and between-group components. Consider, for example, a behavior that decreases the utility of self and increases the utility of others. If others include the entire population, then the utility of those expressing the behavior will be lower than those that do not, and the behavior...

Modeling Studies on Prediction of Putative Pharmacophores

Under selection from repeated sprays of insecticides, individuals possessing biochemical mechanisms that can detoxify the insecticide more rapidly or are less sensitive to it are likely to be favoured. These resistant insects survive doses that would kill normally sensitive individuals. Genes encoding these mechanisms will then be passed on to the succeeding generations, resulting in pest populations that are not controlled effectively. This can lead to farmers increasing the rate or frequency of applications, imposing further selection pressure and ultimately leading to a situation whereby the pests become totally immune. Removal of selection pressure may result in the pest populations regaining some degree of sensitivity, particularly if there is a fitness cost to resistance such as longer development times or reduced over-wintering ability. Usually, however, the population never regains the degree of sensitivity of the na ve population, and often there appears to be little fitness...

Conclusions And Final Remarks

The present approach is based on fitness of sequences into structures. Nevertheless, it is easily extendable to include also sequence similarity, family profiles, secondary structures, and other relevant signals. Because the THOM2 model provides an effective and comparable in performance alternative to pairwise potentials, it can be used as a fast component of fold recognition methods employing pair energies. It is the target of a future work. 5. C. Ouzounis, C. Sander, M. Scharf, and R. Schneider, Prediction of protein structure by evaluation of sequence-structure fitness. Aligning sequences to contact profiles derived from 3D structures. J. Mol. Biol. 232, 805-825 (1993).

The Optimization Criterion

Some assumption must then be made concerning what quantity is being maximized. The most satisfactory is the inclusive fitness (see the section Games between Relatives, below) in many contexts the individual fitness (expected number of offspring) is equally good. Often, as in the second and third of my examples, neither criterion is possible, and some other assumption is needed. Two points must be made. First, the assumption about what is maximized is an assumption about what selective forces have been responsible for the trait second, this assumption is part of the hypothesis being tested. Having considered the phenotype set and the optimization criterion, a word must be said about their relationship to Levins's (51) concept of a fitness set. Levins was explicitly concerned with defining fitness ''in such a way that interpopulation selection would be expected to change a species towards the optimum (maximum fitness) structure.'' This essentially group-selectionist approach led him to...

Protein Fractionation

The same materials and methodology described for desalting are used for protein fractionation. However, selection of matrix and column (see Strategic Planning) is more critical in this procedure, as are the quality of the column packing and control over experimental conditions (e.g., temperature and flow rate). The protocol includes steps for determining the column efficiency (also see unit 8.1) to evaluate the fitness of a packed column for use in protein fractionation.

Optimal Parameter Estimation Using Genetic Algorithms

GA are inspired by the biological process of natural selection, performing selection, crossover and mutation over a population, in order to achieve a global optimum. Instead of searching from general-to-specific hypotheses or from simple-to-complex, genetic algorithms generate successor hypotheses by repeatedly mutating and recombining parts of the best currently known hypotheses. GA are applied to an existing population of individuals, the chromosomes. At each iteration of the genetic process, an evolution is obtained by replacing elements of the population by offspring of the most fitted elements of that same population. In this way, the best fit individuals have a higher probability of having their offspring (that represent variations of itself) included in the next generation. GA evaluates the individuals in the population by using a fitness function. This function indicates how good a candidate solution is. It can be compared with an objective function in classical optimisation....

Docking Programs GOLD

GOLD (genetic optimization for ligand docking) utilizes a genetic algorithm (GA),15,29 that mimics the process of evolution by applying genetic operators to a collection of putative poses for a single ligand (in GA terms, a population of chromosomes). GOLD chromosomes contain four genes. Two of these encode conformational information of the flexible parts of the protein and of the ligand, respectively. Each byte within these genes specifies a rotatable bond. The two remaining genes (feature arrays) encode hydrogen bonds and lipophilic interactions, respectively. Each potential hydrogen-bonding or lipophilic feature of the protein is represented by an array element. Each element either points to a corresponding partner on the ligand or contains an indication that the feature has no partner in the ligand. From the information contained in a chromosome, a 3D pose is generated (referred to as decoding) first a ligand conformation is generated by applying the bond rotations encoded in the...

Combinatorial Library Design

Product-based selection is typically implemented using an optimization technique such as a GA or simulated annealing,152-154 which aims to identify a combinatorial subset directly. For example, a GA has been described in which each chromosome encodes one possible combinatorial subset of a predefined size.153 Thus, consider the design of a two-component combinatorial subset of size nA x nB selected from a possible NA x NB virtual library. Each chromosome consists of nA + nB elements, with each element specifying one possible monomer selected from the appropriate monomer pool. The fitness function quantifies the 'goodness' of the combinatorial subset encoded in the chromosome and the GA evolves new potential subsets in an attempt to maximize this quantity. The fitness function could be designed to maximize the diversity of the subset, using MaxSum, MaxMin, or via a partitioning scheme, or it could be designed to focus the subset around a known target compound, for example, by maximizing...

Docking with Constraints

By introducing a bias during docking it is possible to influence the way poses are generated and which ones are preferentially kept. For example, in the DockIt program,106 one can apply distance constraints between ligand and protein atoms that are subsequently used during pose generation via a distance geometry approach. The GA of the GOLD program107-109 makes it easy to include different types of constraints in the fitness function, thus enabling the generation of biased poses. In the PhDock approach,110 as implemented in DOCK 4.0,111 one can perform pharmacophore-based docking by overlaying precomputed conformers of molecules based on to their largest 3D pharmacophore. The pharmacophore is then matched to predefined site points representing putative receptor interactions. Subsequently, all conformers are docked corresponding to the pharmacophore match and the fit of each individual conformer is scored. The advantage of this approach is twofold speed through a rapid pre-orientation...

Games between Relatives

The central concept is that of ''inclusive fitness'' (33). In classical population genetics we ascribe to a genotype I a ''fitness'' W, corresponding to the expected number of offspring produced by I. If, averaged over environments and genetic backgrounds, the effect of substituting allele A for a is to increase W, allele A will increase in frequency. Following Oster et al. (74) but ignoring unequal sex ratios, Hamilton's proposal is that we should replace W by the inclusive fitness, Z , where where the summation is over all R relatives of I r j is the fraction of J's genome that is identical by descent to alleles in I and Wj is the expected number of offspring of the jth relative of I. (If J I, then equation 6 refers to the component of inclusive fitness from an individual's own offspring.)

Scoring and Binding Energy Estimation

Scoring functions used in ligand design, as well as in ligand docking and virtual screening, are required to guide the sampling processes employed, as well as to estimate the fitness of the protein-ligand complex, usually in the form of a binding energy.93 As a consequence of the huge number of iterations conducted in each simulation, and often the processing of a large number of ligands, such scoring functions must be fast, which invariably means that accuracy is compromised, since several terms involved in the full thermodynamic cycle will be ignored. Nevertheless, scoring functions need to be robust in that they rank solutions highly with favorable steric and electrostatic interactions and rank ligands lower that are not complementary to a particular target, or are in an unfavorable configuration. The balance between hydrophobic interactions and hydrogen bonding, which represent the two main proponents of complex formation, is a key requirement for a successful scoring function...

Discussion and conclusions

This chapter concentrates on efforts to apply perspectives from life history theory in biology to data on contemporary hunters and gatherers. Topics include the allocation of resources between offspring number and fitness, age at first reproduction, lack of balance of fertility and mortality schedules, the special significance of helpers in human adaptation, and contrasting ideas about the evolution of post-reproductive life. These investigations share an interest in ecological contexts that may have shaped the life history parameters. Each attaches primary importance to rich resources that are difficult for juveniles to acquire (meat, deep roots

Multiobjective Optimization

The general idea of multiobjective optimization is to incorporate as much knowledge into the design as possible. Ideally, many factors should be taken into consideration, such as diversity, similarity to known actives, favorable physicochemical and ADME Tox profile, cost of the library, and many other properties. Several groups have developed computational approaches to allow multiobjective optimization of library design 100, 101 . One method developed by researchers from 3-Dimensional Pharmaceuticals (now Johnson & Johnson) employs an objective function that encodes all of the desired selection criteria and then identifies an optimal subset from the vast number of possibilities 101 . The overall architecture of this approach is shown in Figure 15.6. An optimizer (in this case, a serial or parallel implementation of simulated annealing) produces a state (that is, a collection of subsets from one or more chemical libraries), which is evaluated against all of the desired selection...

Comparativeintegrative Creativity

From the perspective of evolutionary biology, something is adaptive if it maximizes the pursuit of ends advantageous to underlying genes. This outlook is not simply survival of the fittest individual the going-on-being of genes is the more powerful motivator. Genetic material survives better in offspring, for individual death is simply a matter of time. By the criterion of inclusive fitness (Hamilton, 1964), perpetuation of one's genes in others (and in the resultant gene pool for the species) is the measure of evolutionary success. Natural selection favors organisms that maximize their inclusive fitness. Each individual pursues its particular path to maximize inclusive fitness. Its aims bring it into conflict with other family members pursuing their paths. To reduce overt conflict with parents whose maximal investment is required, children draw on deep psychodynamic structures analogous to the inborn, linguistic structures (Chomsky, 1972) infants utilize to rapidly learn language....

Activity Guided Design

The methods and applications described up to this point have relied to a greater or lesser extent upon a computational model to guide the library design. An issue referred to above has been the vastness of chemical space the Ugi reaction can give rise to potentially millions of products, there are 64 million possible hexapeptides from the 20 naturally occurring amino acids. Are there alternative strategies for the discovery of active compounds in this vast space One such iterative approach to library design has been proposed and exemplified by several groups.310-312 The idea is simple in principle screen a subset of compounds from a library, measure the biological activity, input this information to an optimization algorithm, and generate the next set of compounds to synthesize and screen. This process is repeated until the desired activity level is reached or no improvement is seen. A GA has been the optimization method of choice. It relies upon a population of individuals, the...

Aspidophorus chiloensis See Poachers

Mental errors, *parasites, predator attacks, or diseases (see Morris etal. 2003 Reimchen 1988, 1992,1997 Sasal and Pampoulie 2000), all of which invariably generate asymmetric injuries. Indeed, many animals, including fishes, generate colour patterns ofintricate symmetry, i.e. in which asymmetries are easily detected. Such a *handicap may help females evaluate the true fitness ofmales.

Batrachus porosissimus See Toadfishes

Competitors and potential predators did not lead to injuries (Reimchen 1988,1992 Barlow 2000, p. 131) - all indicative of good genes. Thus, in animals, symmetrical bodies correlate with increased fitness. In humans, facial symmetry is a necessary (though not a sufficient) condition for the perception of beauty (Edcoff 1999).

Stochastic Explanation of GA

Let the population size be N, which contains mH (t) samples of schema H at generation t. Among the selection strategies, the most common is the proportional selection. In proportional selection, the number of copies of chromosomes selected for mating is proportional to their respective fitness values. Thus, following the principles of proportional selection 17 , a string i is selected with probability where fi is the fitness of string i. Now, the probability that in a single selection a sample of schema H is chosen is described by

Higherlevel Generalization

Fitness is the supervenient biological property par excellens. What do a fit zebra, a fit dandelion, and a fit bacterium have in common Presumably, nothing much at the level of their physical properties. However, this has not prevented evolutionists from theorizing about fitness. I have already mentioned Fisher's theorem and there are lots of other lawful generalizations that describe the sources and consequences of fitness differences (Sober 1984). It might be objected that these generalizations are a priori, and so are not laws, properly speaking. This raises the question of whether laws must be empirical, but let us put that issue aside. If the multiple realiz-ability of a property makes it ''complicated,'' then fitness is complicated. And if the complexity of a property makes it impossible for us to discover qualitative, counterfac-tual supporting, and explanatory generalizations about the property, then we should have none available about fitness. But we do, as...

Types Of Models Used In Drug Discovery And Development

Models can be characterized in many ways, in what might be called dimensions. Some dimensions are a matter of degree. These include ranges such as simple to complex, phenomenological to mechanistic, descriptive to predictive, and quantitative to qualitative. Other dimension types are discrete and either or steady-state or dynamic, deterministic or stochastic. Using these descriptive dimensions facilitates understanding the differences between models and their fitness for specific uses.

Applications of GA in Intelligent Search

The navigational planning for robots is a search problem, where the robot has to plan a path from a given starting position to a goal position. The robot must move without hitting an obstacle in its environment (fig. 15.13). So, the obstacles in robot's work-space act as constraints to the navigational planning problem. The problem can be solved by GA by choosing an appropriate fitness function that takes into account the distance of the planned path-segments from the obstacles, length of the planned path and the linearity of the paths as practicable.

Stochastic approaches

Two bit strings are used to represent a docking configuration. The first string contains the ligand conformations defining the torsion angle of each rotatable bond. The second string contains the hydrogen bond mapping between the relevant protein and ligand atoms. The fitness function takes into account the evaluation of hydrogen bonds, internal energy of the ligand and the protein-ligand vdW energy, together with any scoring functions associated with the docking run.

Cancer initiation onehit and twohit stochastic models

The one-hit model can be relevant for the description of an oncogene activation, or cancer initiation in patients with familial disorders, where the first allele is mutated in the germ line, and the inactivation of the second allele leads to a fitness advantage of the cell. In these cases, we can assume r 1. In the more general case, we can view the one-hit model as the process of any one genetic alteration, resulting in a advantageous (r 1), disadvantageous (r 1) or a neutral (r 1) mutant. The Moran process. One can envisage the following birth-death process (called the Moran process). At each time step, one cell reproduces, and one cell dies. We set the length of each time step to be 1 N, so that during a unit time interval, N cells are chosen for reproduction and N cells die. We assume that all cells have an equal chance to die (this is equal to 1 N). On the other hand, reproduction happens differentially depending on the type, and the relative probability of being chosen for...

Prediction of Phenotype from Other Sources of Data

Advantages Decision Tree Proteins

Parsons et al. (2004) use phenotypic experiments to test sensitivity of yeast singlegene mutant strains to different drugs, building a 'chemical-genetic profile' for each drug, indicating which genes interact with the drug and can buffer the drug target. Genes that appear in the profiles for more than one drug can be said to be involved in multi-drug resistance, and they identified 65 genes involved in drug resistance to at least four compounds. They then went on to make double-gene mutants for selected genes, and scored these for fitness, in order to create profiles that could be compared to the chemical-genetic profiles. The chemical-genetic profiles indicate gene-drug interaction, and the double-mutant genetic profiles indicate gene-gene interaction. Similarities between profiles could be used to identify target pathways. For example, 75 genes showed sensitivity to the drug flucanzole. ERG11 is a target of flucanzole, and making double mutants with this gene showed that 13 of the...

Carcharias megalodon See Megatooth shark

As it turns out, maintaining functional eyes in an environment where vision provides no selective advantage is injurious, because this costs metabolic energy, which may better be used elsewhere (see Oxygen), e.g. for olfactory and tactile receptors and the associated parts of the *brain (Poulsen 1963). Thus, it is not simple disuse that causes the eye of successive generations of cavefish to atrophy, but competitions with variants whose fitness is high because of their atrophied eyes. This is also the reason why the degeneration of the eyes, well studied in Astyanax mexicanus, a *characin, follows highly predictable steps (G nermont et al. 1996), and stops when it starts compromising other, ontogenetically related, and still useful organ systems.

Optimization Techniques

As indicated earlier, the computational intractability of exact methods for selecting the maximally diverse subset of compounds lead to the development of the DBCS and sphere exclusion approximate methods. An alternative approach is to use an optimization algorithm such as a genetic algorithm or simulated annealing. These algorithms can provide effective ways of sampling large search spaces and hence they are well suited to compound selection, provided that they are used with efficient methods of calculating diversity. For example, the Monte Carlo method has been combined with simulated annealing to select a diverse subset of compounds.170 An initial subset is chosen at random and its diversity is calculated. A new subset is then generated from the first by replacing some of the compounds with others chosen at random. If the new subset is more diverse than the previous subset it is accepted for use in the next iteration if it is less diverse, then the probability that it is accepted...

Worksite Health Promotion

Health promotion at the worksite covers a wide variety of activities, including exercise and fitness, stress management, smoking cessation, and cholesterol reduction. Specific programs targeting women may include prenatal care, parenting, breast examinations, and mammograms.

P450mediated resistance evolution

Therefore, an alternative hypothesis is that the multitude of P450 genes, whose expression is inducible and therefore not strongly expressed in most developmental stages tissues, constitute a ''reservoir'' in which mutations affecting expression levels can be selected by insecticide exposure. In the field, this can lead to selective ''sweeps'' of these most adapted mutations as seen for the global predominance of the Rutgers and Cyp6g1 Accord haplotypes in house flies and fruit flies. These mutations would typically be loss-of-function mutations, which inactivate the fine level regulation of expression and therefore increase overall expression of a random P450 gene. If its product happens to metabolize the insecticide, even marginally, this may constitute a selective advantage for the organism. Loss-of-function mutations in the large target of negative regulatory sequences are predicted to be more frequent than gain-of-function mutations (in the smaller open reading frame) that...

National Association of Senior Health Professionals NASHP

NASHP is a new Web-based membership organization specifically designed to address the unique needs and special interests of professionals in the rapidly growing field of senior health. Membership is open to any professional who works with older adults in the public, private, and nonprofit sectors, including hospital-based senior membership program directors, health educators, health promotion staff, activity professionals, and fitness program and health club staff. Members are provided with instant access to important information related to the association and its goals.

Park and Levitt Decoys

Another measure of the fitness of the scoring functions is to evaluate the RMSD of the lowest-energy structure in each decoy set. The results are summarized in Table II. The RMSD of the lowest-energy decoy range from 0.94 A to 2.20 A with an average RMSD of 1.9 A. These decoys fall within the nativelike designation. The average energy deviation from the native energy is + 79.5 kcal mol, which represents an average deviation of + 2 from the native total energy values. As we shall see below, not all scoring functions examined yield decoy energies consistently higher than the native energy.

Structure of Multiobjective Problem Solving

Using stochastic methods, the generation of scenarios can be performed by discretizing the continuous probability distributions or by Monte Carlo type simulation techniques.3 Multiobjective evolutionary algorithms (MOEAs) represent perhaps the most popular alternative in multiple objective optimization. MOEA methods use genetic algorithm approaches to generate all the Pareto-front solutions.4'5 The selection of individuals is based on their Pareto optimality. There are several ways of performing this Pareto ranking, leading to several well-known approaches under the category MOEA. These include multiobjective genetic algorithm (MOGA).6,7 Multiple objectives are treated independently, and the fitness ranking of a genetic algorithm is replaced by Pareto ranking, which is based on the concept of dominance. A nondominated solution is one where an improvement in one objective results in deterioration in one or more of the other objectives when compared with the other solutions in the...

Applications in Cheminformatics

Wright etal.19 investigate the effect of optimizing library size simultaneously with other library characteristics such as diversity and drug-like physicochemical properties. Their system, MoSELECT.II, has been applied to two different virtual libraries a two-component aminothiazole library consisting of 12 850 products generated from 74 R-bromo-ketones coupled with 170 thioureas, and a four-component benzodiazepine library consisting of 256 036 products. The method uses a niching technique that uses fitness sharing to improve diversity of the solutions thus avoiding MOGA's tendency to genetic drift where they converge toward a single solution. Fitness sharing and its advantages relating to MOGA are discussed by Horn et al.8 MoSELECT.II's implementation of fitness sharing ensures that nondominated individuals are evenly distributed on the Pareto surface.

Limitations of Numerical Multiobjective Algorithms

Several situations can generate problems that can limit the applicability of these methods and in what follows we shall briefly mention a few. First, the need to have a large number of fitness evaluations requires a rapid simulation method. In situations where one lacks the possibility of performing fast simulations (i.e., experimental context), the number of evaluations of the fitness scores need to be dramatically reduced, hence impacting the viability of the convergence of the above discussed methods. On the contrary, problems with large numbers, such as library design problems where the method is asked to select out 250000 compounds, a subset that optimizes a few objectives, are well adapted. However, even in the latter, if the number of objectives grows, then again nonconvexity bias will interfere with the search and adversely impact the quality of the pareto-set. Overall, in problems where it is not easy to simulate a particular potential solution in a timely fashion, MOEAs are...

Ruth Mace And Clare Holden

Matrilineality has puzzled evolutionary anthropologists because it is not clear that male fitness is enhanced by passing resources on to a sister's son in preference to the man's own son. Tensions between men wishing to invest in their own children rather than in the mamtrilineal heirs are commonly reported. In the first descriptions of matrilineal societies by Western anthropologists (who were struck by the differences from their own culture), marriage and marital fidelity in matrilineal societies appeared relatively weak. If paternity uncertainty were very high, then fitness might be better enhanced by investing in your uterine sister's sons than in your wife's sons. But Hartung (1985) has demonstrated that paternity uncertainty would have to be at unrealistically high levels for this condition to hold. Hartung shows that matrilineality, whilst not adaptive for males, is adaptive for females under any level of paternity certainty below 1. This is because a grandmother's matrilineal...

Novel Variable Selection Methods

In QSAR studies of large data sets particularly, variable selection and model building is a difficult, time-consuming, and ambiguous procedure. Kubinyi has reviewed methods such as stepwise regression procedures, neural networks, cluster significance analysis, or genetic algorithms for variable selection (121). He also described a simple and efficient evolutionary strategy, MUSEUM (Mutation and Selection Uncover Models), for variable selection. Random mutation (first by addition or elimination of very few variables, then by simultaneous random additions, eliminations, and or exchanges of several variables at a time) leads to new models that can be evaluated by appropriate fitness functions. In contrast to common genetic algorithm procedures, only the fittest model is stored and used for further mutation and selection, leading to better and better models. sentation via genetic algorithm (GA) to determine relevant variables for modeling (128). The fitness function in the variable...

Conclusion and Prospects

When significantly more data are obtained on the catalytic competence of a wide variety of insect P450 enzymes, it will become easier to understand the way in which insects maintain a wide repertoire of P450 genes. If positive selection of a few P450 genes can lead to specialized enzymes in oligopha-gous species (Li et al., 2003), is this an evolutionary dead-end Do the P450 enzymes with ''broad and overlapping'' specificity serve as a perpetual reservoir where some genes, because of their pattern of expression or inducibility or catalytic competence, can then serve as templates for the evolution of a new branch of specialized enzymes Does this ''primordial soup'' perpetuate itself simply by a neutral process of intense gene duplication or are new chemical insults of the environment frequent enough to positively select for a minimal number of ''jack-of-all-trades'' P450 enzymes How do P450 genes get recruited into physiological networks and biosyn-thetic pathways The gap between...

Germination The 1960s

The users' room at the computer centers echoed with the clunk-clunk-clunk of card punches that encoded data as little rectangular holes in the so-called IBM cards see reference 11 . The cards were manufactured in different colors so that users could conveniently differentiate their many card decks. As a by-product, the card punches produced piles of colorful rectangular confetti. There were no Delete or Backspace keys if any mistake was made in keying in data, the user would need to begin again with a fresh blank card. The abundance of cards and card boxes in the users' room scented the air with a characteristic paper smell. Programs were written in FORTRAN II. Programs used by the chemists usually ranged from half a box to several boxes long. Carrying several boxes of cards to the computer center was good for physical fitness. If a box was dropped or if a card reader mangled some of the cards, the tedious task of restoring the deck and replacing the torn cards ensued....

Cellular origins of cancer

Chapter 3 presented an extensive stochastic analysis of a two-hit model. In particular we calculated the probability of creating a double-mutant as a function of time, depending on the population size and the relative fitness of the intermediate type. Chapter 4 made the first attempt to apply this model to real-life carcinogenesis, by taking account of specific features of sporadic and familial colorectal cancers. One important consideration which was not included in the analysis so far is the population structure. In Chapters 3 and 4, the population of cells was completely homogeneous with respect to the patterns of mitosis apoptosis. In other words, cells were only characterized by their fitness , which was a function of acquired mutations. In some cases, this is not enough to grasp the essential dynamics of the system. An example is the colonic epithelial tissue. There, when talking about the dynamics of cell division and mutations, we may have to take into account the fact that...

Resistance Mechanism for Resistance and Resistance Potential

As documented by Moffit et al. (1988) and Sau-phanor et al. (1998), the codling moth C. pomonella shows very high levels of resistance to diflubenzuron in the USA and France. In southern France, failure in C. pomonella control was observed for several years, revealing a 370-fold resistance for difluben-zuron and cross-resistance with two other BPUs, teflubenzuron (7-fold) and triflumuron (102-fold), as well as to the ecdysone agonist, tebufenozide (26fold) (Sauphanor and Bouvier, 1995). Interestingly, resistance to diflubenzuron was linked to cross-resistance to deltamethrin. In both cases, enhanced mixed-function oxidase and GST activities are involved in resistance, rather than target site modification. In addition, a fitness cost described in both resistant strains was mainly associated with metabolic resistance (Boivin et al., 2001). Finally, a lack of relationship between ovicidal and larvicidal resistance for diflubenzuron in C. pomonella may be due to different transport...

Two Other Criticisms of the Multiple Realizability Argument

It might interest philosophers of mind who have these worries about multiply realized psychological properties to consider the multiply realized properties discussed in evolutionary biology. In cognitive science, it is difficult to point to many present-day models that are well-confirmed and that are articulated by describing multiply realizable properties this is mostly a hoped-for result of scientific advance. However, in evolutionary biology, such models are extremely common. Models of the evolution of altruism (Sober and Wilson 1998), for example, use the concept of fitness and it is quite clear that fitness is multiply realizable. These models have a useful generality that descriptions of the different physical bases of altruism and selfishness would not possess.

Brains Are Composed Primarily of Adaptive Problem Solving Devices

Adapted to the past The human brain, to the extent that it is organized to do anything functional at all, is organized to construct information, make decisions, and generate behavior that would have tended to promote inclusive fitness in the ancestral environments and behavioral contexts of Pleistocene hunter-gatherers and before. (The preagricultural world of hunter-gatherers is the appropriate ancestral context because natural selection operates far too slowly to have built complex information-processing adaptations to the post-hunter-gatherer world of the last few thousand years.)

Heuristic Search for OR Graphs

Most of the forward reasoning problems can be represented by an OR-graph, where a node in the graph denotes a problem state and an arc represents an application of a rule to a current state to cause transition of states. When a number of rules are applicable to a current state, we could select a better state among the children as the next state. We remember that in hill climbing, we ordered the promising initial states in a sequence and examined the state occupying the beginning of the list. If it was a goal, the algorithm was terminated. But, if it was not the goal, it was replaced by its offsprings in any order at the beginning of the list. The hill climbing algorithm thus is not free from depth first flavor. In the best first search algorithm to be devised shortly, we start with a promising state and generate all its offsprings. The performance (fitness) of each of the nodes is then examined and the most promising node, based on its fitness, is selected for expansion. The most...

Stochastic Variation in Offspring Number

Let us leave the question of short-term versus long-term behind and turn now to the question of whether fitness should be defined as a mathematical expectation. This is not an adequate definition when there is stochastic variation in viability or fertility. Dempster (1955), Haldane and Jayakar (1963), and Gillespie (1973, 1974, 1977) consider stochastic variation among generations Gillespie (1974, 1977) addresses the issue of within-generation variation. These cases turn out to have different mathematical consequences for how fitness should be defined. However, in both of them, selection favors traits that have lower variances. In what follows, I will not attempt to reproduce the arguments these authors give for drawing this conclusion. Rather, I will describe two simple examples that exhibit the relevant qualitative features. The trait with the lower variance can be expected to increase in frequency. The appropriate measure for fitness in this case is the geometric mean of offspring...

Criticisms of the grandmother hypothesis

Current evidence suggests patrilocality as a conservative hominoid trait (Foley and Lee, 1989). Would grandmothering work as well in patrilocal groups as in the matrilocal groups it has been studied in The authors would rank grandmother's fitness benefit accruing from help to children of beneficiaries as greatest from help to daughter sister niece son nephew because of relatedness and paternity uncertainty. (Grandmother as mate guard is a role we have not examined. It might have interestingly different implications for life history.) For grandmothering to win over continued births, the only hopeful candidate would be help to daughter help to others is too heavily discounted. But help to any of these might be adequate to select for delayed senescence. Thus, the grandmother hypothesis could apply to either matrilocal or patrilocal settings. But grandmothers benefit most by living with their daughters and should favour matrilocality. Provisioning enables older juveniles to help their...

Notice to the Reader

The publisher and the authors make no representations or warranties of any kind, including but not limited to the warranties of fitness for a particular purpose or merchantability nor are any such representations implied with respect to the material set forth herein, and the publisher and the author take no responsibility with respect to such material. The publisher and the author shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the reader's use of, or reliance upon, this material.

In the Beginning

There is strong neuroscience evidence of many kinds suggesting that the initial phase of the story of life on Earth ended about 580 million years ago with a large, rapid, and sustained (to the present) increase in atmospheric oxygen concentration (Canfield et al. 2007, Fike et al. 2006, Kerr 2006). Immediately thereafter, a profusion of macroscopic moving animals emerged (the Cambrian explosion of species). The fitness advantages of complex, purposeful movement rapidly drove the evolutionary development of articulated bodies, muscle complements, and the brains and sensory systems needed to purposefully run them.


Protein threading (Bowie et al., 1991 Godzik et al., 1992 Jones et al., 1992 Sippl and Weitckus, 1992 Bryant and Altschul, 1995 Alexandrov et al., 1996 Fischer et al., 1996 Xu et al., 1998 Crawford, 1999) is the most promising and practical tool for fold recognition as demonstrated in the CASP tests. The basic idea of threading can be summarized as follows. Given a query protein sequence, s, of unknown structure, threading searches all structure templates, T, to find the best fit for s. A threading requires four components (Smith et al., 1997) (1) a library, T, of representative three-dimensional protein structures for use as templates (2) an energy function to describe the fitness between s and t, where t is a single template in T (3) a threading algorithm to search for the lowest energy among the possible alignments for a given s-t pair and (4) a criterion to estimate the confidence level of the predicted structure.

S Itchy 9 Thioitchy

And fitness of a library Crossovers occur in regions of short (0-5 bases) sequence homology Single hybridization event reduces the mismatching sometimes seen in PCR-based methods are to be screened in yeast Only one crossover per hybrid per round (low diversity 84 library, but may iterate or combine with homologous recombination methods to improve crossovers) Limited to two parents of equal length Low-fitness hybrids (two thirds may contain frame-shift) May induce aa deletions or duplications at junctions Same cons as for SHIPREC 85


Sedentary patients who are unmotivated to change their physical activity behaviour should then benefit from a brief consciousness-arousing session and be invited to read related information. Those who are motivated should benefit from a structured counselling session, receive written information, and a physical activity prescription using the existing structures within their environment (walking groups, fitness centres etc.).


A science may well progress even though its practitioners are unable to account for aspects of its foundations in any illuminating way. We believe that this has been the case with evolutionary theory, but that the propensity analysis of fitness which we have described captures the implicit content in biologists' usage of the term. The propensity interpretation allows us to reconstruct explanations of microevolutionary phenomena in such a way that these explanations appear to be entirely respectable and noncircular. By their form, and by inspection of the premises and conclusion, such explanations appear to satisfy Hempelian adequacy requirements for explanations, and even appear to incorporate recent modifications of the Hempelian model for inductive explanations (Coffa 1974). We chose an example of microevolutionary change, since we wanted the least complicated instance possible in order to illuminate the form of explanations utilizing fitness ascriptions. We know of no reason to...

Elliott Sober

The concept of fitness began its career in biology long before evolutionary theory was mathematized. Fitness was used to describe an organism's vigor, or the degree to which organisms ''fit'' into their environments. An organism's success in avoiding predators and in building a nest obviously contributes to its fitness and to the fitness of its offspring, but the peacock's gaudy tail seemed to be in an entirely different line of work. Fitness, as a term in ordinary language (as in ''physical fitness'') and in its original biological meaning, applied to the survival of an organism and its offspring, not to sheer reproductive output (Cronin 1991, Paul 1992). Darwin's separation of natural from sexual selection may sound odd from a modern perspective, but it made sense from this earlier point of view. Biologists came to see that this limit on the concept of fitness is theoretically unjustified. Fitness is relevant to evolution because of the process of natural selection. Selection has an...


The threading approach 1-8 to protein recognition is a generalization of the sequence-to-sequence alignment. Rather than matching the unknown sequence Si to another sequence S, (one-dimensional matching), we match the sequence S, to a shape Xj (three-dimensional matching). Experiments found a limited set of folds compared to a large diversity of sequences. A shape has (in principle) more detectable ''family members'' compared to a sequence, suggesting the use of structures to find remote similarities between proteins. Hence, the determination of overall folds is reduced to tests of sequence fitness into known and limited number of shapes.

Genetic algorithms

A genetic algorithm performs its search by analogy to biological evolution.77 Possible solutions are represented as alleles in a chromosome, one chromosome per molecule. The genetic operators of mutation and crossover operate to optimize some fitness (scoring) function for the whole set of individuals.78 For example, in the GASP program each molecule is represented by one chromosome that contains alleles to describe each torsion angle and a second set of alleles that identify which atom is matched to a particular atom in a reference molecule. The fitness function of the genetic algorithm is a weighted combination of (1) the number and the similarity of the features that have been overlaid (2) the volume integral of the overlay and (3) the van der Waals energy of the molecular conformations defined by the torsion angles encoded in the chromosomes.79 Other programs use different chromosomes and fitness functions. All pharmacophore hypotheses are just that, hypotheses. For a scientist,...


There is no reason for people with kidney failure to avoid strenuous activity. Patients can improve their exercise capacity considerably with regular workouts. Symptoms diminish and quality of life improves. When predialysis patients regularly exercised for four months, breathing capacity, muscular strength, and blood pressure all improved. There is no evidence, however, that exercise can defer dialysis current evidence indicates that progression is unaffected. The general health benefits of regular exercise have been widely publicized and include lowering blood pressure, lowering blood cholesterol level, and weight loss.

Age at first birth

Like Stearns and Koella (1986), Hill and Hurtado sought the strategy that maximised fitness, measured as r (intrinsic rate of increase). Stearns (1992 p. 148) points out that Kozlowski and Wiegert (1987) examined maximisation of lxmx and obtained the prediction that faster growth predicted later maturity. This point, apparently commonplace to life history theorists, is noted as a warning to us 'end-users' that the field is complex, in flux, and there is as yet no single 'right' model. They link these observations of developing hunting success to the idea that humans mature late because this allows them more time to acquire fitness-enhancing skills (Lancaster and Lancaster, 1983 Bogin, 1990 Lancaster, 1997). Kaplan's interest in human capital theory (1994), often used to discuss the costs and benefits of staying on at school, may lead to a more explicit version of this view. These authors have argued in another direction (Blurton Jones, Hawkes and O'Connell, 1997 Hawkes, O'Connell and...


Humans are expert at recruiting and distributing help. Hill and Hurtado suggest that many costs and benefits of alternative ways of behaving, growing and reproducing may be rendered unmeasurable by the ability of the individual who 'made an error' to cover it by recruiting help from kin, who also benefit from helping to remedy the miscalculation. Thus, a grandmother gains more fitness by going to go to help her daughter who bore too many children too fast (and thus risks being unable to feed them) than to her daughter who has few (depending on why the latter has few ). Grandmother's decision then reduces the effect of her daughter's 'miscalculation'. If instead the first daughter has more children because she


Reproductive senescence. In Reproduction in Mammals 4 Reproductive Fitness, ed. C.R. Austin and R.V. Short, pp. 210-33. Cambridge Cambridge University Press. Pennington, R. and Harpending, H.C., (1988). Fitness and fertility among Kalahari Kung. American Journal of Physical Anthropology 77, 303-19.

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Genetic algorithms belong to the more general class of evolutionary algorithms that have become an important optimization methodology within computational chemistry.114 GAs are loosely connected with the principles of Darwinian evolution as shown in the general process flow in Figure 7 and much of the terminology is borrowed from this field.115 Thus, there is the concept of a population that evolves under the constraint of some user-defined objective function. The objective function is used to compute a score or fitness for each individual within the population that is used, in turn, to assess the likelihood of that individual generating offspring at the next generation. The fitter the individual the more likely it is to breed. Each individual is represented by a chromosome (genotype) that encodes the particular problem to be optimized in a series of genes. At each generation chromosomes can mutate (one individual generates one offspring) or can breed with another individual via a...


Rosenberg's brief for lawlessness rests on an entirely different set of arguments than Beatty's. Rosenberg (1994) uses the idea of supervenience to argue that, with one exception, there are no laws in biology. The one genuine law is what Rosenberg calls ''the theory of natural selection,'' by which he means Mary Williams' (1970) axiomati-zation. Rosenberg represents this axiomatization as saying that (i) there is an upper bound on the number of organisms in a generation, (ii) each organism has a fitness value, (iii) fitter traits increase in frequency and less fit traits decline, and (iv) populations show variation in fitness unless they are on the brink of extinction (p. 106). I want to raise two questions about this axiomatization. Proposition (iv) is probably true, but I do not see why the existence of variation in fitness should be regarded as a law. Statement (iii) is false if fitness means expected number of offspring and if fitness means actual number of offspring, it also is...

Bi2 Bi 2

(c) Heuristic Search Classically heuristics means rule of thumb. In heuristic search, we generally use one or more heuristic functions to determine the better candidate states among a set of legal states that could be generated from a known state. The heuristic function, in other words, measures the fitness of the candidate states. The better the selection of the states, the fewer will be the number of intermediate states for reaching the goal. However, the most difficult task in heuristic search problems is the selection of the heuristic functions. One has to select them intuitively, so that in most cases hopefully it would be able to prune the search space correctly. We will discuss many of these issues in a separate chapter on Intelligent Search.

Exercise at Altitude

Altitude training has become more popular among athletes, at least in sports with a high demand for cardiorespiratory fitness. The oxidative stress and antioxidative defenses in hypoxia may be different from that at sea level, and it has been suggested that physical exercise at altitude might result in even more accelerated formation of free radicals and lead to even greater oxidative stress.40 This hypothesis is supported by one study, where the formation of ethane and n-pentane by lipid peroxidation increased as the concentration of oxygen in the ambient air decreased.41 Similarly, athletes had elevated levels of serum diene conjugation after 1 to 2 weeks stay at natural moderate altitude (1650 m above sea level) both before and after a skiing race (25 and 30 , respectively) when compared to the sea level.42 In that study, the serum antioxidant potential tended to be lower

Subset Selection

Genetic algorithms are modeled after natural selection and search for an optimal solution to a problem by allowing a population of individual solutions to evolve, subject to a fitness constraint. In the present case, the candidate solutions are individual combinatorial libraries that are subsets of the full virtual library, and the fitness constraint is calculated using a suitable fitness function. Individual libraries are specified by encoding the candidate reagents for each dimension of a library as a gene on a chromosome each gene is a list of binary variables that indicate the presence or absence of the corresponding reagent in the individual library. By specifying which reagents are present along each gene, the resulting library can be readily deduced. An initial population of libraries is generated by randomly setting the desired number of reagents in each gene as present, and then point-mutations and cross-over events among compatible genes are allowed in the population to...

Scalar Objective

Quantitative structure-activity relationship (QSAR) equations are standard examples in cheminformatics where an overall fitness score is developed as a weighted sum of numerous descriptors. In docking, the score includes ligand internal energy, interaction energy, and entropic considerations in the form of a weighted sum of terms. Typically, the score is developed empirically by analyzing a set of examples and deriving a weighted sum. The weights are 'fitted' to the learning set and may not necessarily be relevant or precise for other complexes. A precautionary approach is to use the individual contributions from distinct terms for ranking, e.g., one seeks 'good' van der Waals and electrostatic contributions but one is not quite sure of how these two should be scaled to become additive.2 However, an effective method for working with multiple objectives is desirable.

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Spartans Routine

Fitness is the biggest issue of todays society because technology has improvised our lives so much that people do not move a lot and this lazy working routine and tiring mind works make people unfit physically.

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