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PubMed2005

Evolution kinetics and phase transitions of complex adaptive systems.

Motivated by the fact that a population of competing agents never set up a true stationary distribution, we propose a theory of evolution kinetics for complex adaptive systems. The formula derived for the survival probability is used to describe different phases in the population evolution when the prize-to-fine ratio as well as time changes. A kinetic phase diagram is obtained to show the phase boundaries for the self-segregating region, the intermediate region, and the clustering region. The kinetic evolutionary equations of strategy distribution are also established and used to give the root-mean-square separation of strategy distribution. It is revealed that the rootstock of the phase transitions is ascribed to the cooperation and competition among agents with different gene values for a limited resource.

Adaptation, Physiological↗
PubMed1980

The aquatic ape theory reconsidered.

Hardy's Aquatic Ape Theory (AAT) proposes that man progressed phylogenetically to the two-legged hairless creature that he is today via a semi-aquatic diversion which probably began during the Pliocene or perhaps as early as the Miocene era. It revolutionizes the human evolutionary story and in the process, challenges the classical anthropoid theory which has been the dominant theory of evolution since the time of Darwin. Possible reasons for the existance of many of man's previously unexplained characteristics (bipedalism, hairlessness, subcutaneous fat, bradycardia and others) is resolved without the proposal of any new or unreasonable hypotheses. Yet the AAT has been largely ignored. Morris and Morgan have supported the theory in the face of considerable criticism. This paper is a review of the theory and a collection of some of the opposing views presented by contemporary orthodox evolutionists.

Animals↗
PubMed2001

Fast Monte Carlo algorithm for site or bond percolation.

We describe in detail an efficient algorithm for studying site or bond percolation on any lattice. The algorithm can measure an observable quantity in a percolation system for all values of the site or bond occupation probability from zero to one in an amount of time that scales linearly with the size of the system. We demonstrate our algorithm by using it to investigate a number of issues in percolation theory, including the position of the percolation transition for site percolation on the square lattice, the stretched exponential behavior of spanning probabilities away from the critical point, and the size of the giant component for site percolation on random graphs.

Journal Article↗
PubMed1983

On estimating the difference between two probabilities, with special reference to clinical trials.

The problem of estimating the difference between the probabilities of 'success' for two binomial experiments is considered. Confidence intervals based on large-sample theory are constructed and some of their properties are compared with those of a simple technique based on exact distributions. It is shown that the former method is superior to the latter, both theoretically and practically.

Biometry↗
PubMed2006

Measures for the assessment of fuzzy predictions of protein secondary structure.

Many of the recent secondary structure prediction methods incorporate the idea of fuzzy set theory, where instead of assigning a definite secondary structure to a query residue, probability for the residue being in each of the conformational states is estimated. Moreover, continuous assignment of conformational states to the experimentally observed protein structures can be performed in order to reflect inherent flexibility. Although various measures have been developed for evaluating performances of secondary structure prediction methods, they depend only on the most probable secondary structures. They do not assess the accuracy of the probabilities produced by fuzzy prediction methods, and they cannot incorporate information contained in continuous assignments of conformational states to observed structures. Three important measures for evaluating performance of a secondary structure prediction algorithm, Q score, Segment OVerlap (SOV) measure, and the k-state correlation coefficient (Corr), are deformed into fuzzy measures F score, Fuzzy OVerlap (FOV) measure, and the fuzzy correlation coefficient (Forr), so that the new measures not only assess probabilistic outputs of fuzzy prediction methods, but also incorporate information from continuous assignments of secondary structure. As an example of application, prediction results of four fuzzy secondary structure prediction methods, PSIPRED, PROFking, SABLE, and PREDICT, are assessed using the new fuzzy measures.

Computer Simulation↗
PubMed1997

The human hepatocyte nuclear factor 3/fork head gene FKHL13: genomic structure and pattern of expression.

We describe the isolation and characterization of the cDNA for FKHL13, the human homologue of the mouse hepatocyte nuclear factor 3/fork head homologue 4 (HFH-4) gene, a member of the HNF-3/fork head (also called winged helix) gene family. Members of this gene family contain a conserved DNA binding region of approx. 110 amino acids and are thought to play an important role in cell-specific differentiation. Previous analysis of the mouse and rat HFH-4 cDNAs revealed a distinct pattern of expression for this gene, suggesting that the gene plays an important role in the differentiation of lung and oviduct/ampulla epithelial cells and testicular spermatids. Analysis of the human FKHL13 gene confirmed this pattern of expression. We also found expression in adult human brain cortex, which we were able to confirm for the mouse. The expression pattern of FKHL13/HFH-4, confined to cilia/flagella-producing cells, leads us to believe that the gene plays an important role in the regulation of axonemal structural proteins. We show that the human gene for FKHL13 lies on chromosome 17 (comparison with the chromosomal location of the mouse gene strongly suggests 17q22-q25) and that the gene, which is approx. 6 kb, contains a single intron disrupting the fork head DNA binding domain. Such a disruption of a functional unit provides strong evidence for the theory of intron insertion during gene evolution. The expression of the gene is probably controlled by the CpG island, which is located in the promoter region of the gene. We also demonstrate that the FKHL13 gene is highly conserved among a wide variety of species, including birds.

Adult↗
PubMed1978

Allotypes of IgM and IgD receptors in the mouse: a probe for lymphocyte differentiation.

Antibodies to IgD and IgM are present in many mouse alloantisera made against lymphocytes. Antibodies to IgM are also present in a small minority of conventional antiallotype sera made against pertussis/anti-pertussis complexes. These antibodies reflect different allelic forms of IgD and IgM in different mouse strains, and allowed the mapping of the delta- and mu-chain genes (Ig-5 and Ig-6, respectively) to the heavy-chain complex. The variable portions of IgM and IgD receptors on individual cells bearing both chains are similar or identical. Both receptors show allelic exclusion and come from the same chromosome on individual cells (haplotype exclusion). It is suggested that very early in B lymphocyte differentiation there is a commitment to a given chromosome, and translocation of one copy of a given variable region gene to each heavy-chain gene. Subsequent switches of immunoglobulin class then involve differential gene activation. Immature B cells possess IgM receptors only and mature into cells bearing both IgM and IgD receptors. After activation with antigen, IgD is probably lost. These findings are discussed within the framework of the clonal abortion theory of B-lymphocyte tolerance.

Animals↗
PubMed1983

Dissociable effects of d-amphetamine, chlordiazepoxide and alpha-flupenthixol on choice and rate measures of reinforcement in the rat.

The role of reinforcers in influencing choice was studied by use of a schedule that included a random intermixing of reinforced and explicitly non-reinforced components. The just-reinforced response had a high likelihood of being repeated (win-stay), although there was no differential reinforcement for doing so, whereas responses just followed by explicit non-reinforcement had a very low probability of repetition (lose-stay). Non-parametric indices based on the theory of signal detection were used to derive a choice measure of reinforcement which was independent of alterations in average response rate. Treatments with d-amphetamine (0.2-4.5 mg/kg), chlordiazepoxide (0.25-16 mg/kg) and alpha-flupenthixol (0.03-0.6 mg/kg) showed that changes in the choice measure could be dissociated from changes in the response rate. These findings were supported by extinction and satiation tests.

Animals↗
PubMed1992

Comparison between HLA-DRB and DQ DNA sequences and classic serological markers as type 1 (insulin-dependent) diabetes mellitus predictive risk markers in the Spanish population.

The question of HLA susceptibility to Type 1 (insulin-dependent) diabetes mellitus remains unresolved. In the present study, 127 diabetic patients and 177 unrelated control subjects have been analysed for their class I and class II serological antigens, class II (DR, DQ) DNA restriction fragment length polymorphisms and DQA1 and B1 exon-2 nucleotide sequences and their corresponding amino acid residues. By using the aetiologic fraction (delta) as an almost absolute measure of the strongest linkage disequilibrium of an HLA marker to the putative Type 1 diabetes susceptibility locus, it has been found that the strength of association of the HLA markers may be quantified as follows: DR4 less than DR3 less than DR3 or DR4 less than non-Aspartate 57 beta DQ and Arginine 52 alpha DQ less than Arginine 52 alpha DQ. Thus, molecular HLA-DQ markers appear to be more accurate as susceptibility markers than the classic serologically defined ones (DR3 and DR4); however, any effect of DQ markers disappears when non-DR3/DR4 individuals are considered, suggesting that DR factors (or others in between DQ and DR) are also important. In addition, a dominant non-Aspartate 57 beta DQ susceptibility theory does not hold (but a recessive one does) in our diabetic population (probably due to the high frequency of the protective DR7-non-Aspartate 57 beta DQ haplotypes); Arginine 52 alpha DQ is the best single HLA marker found in our population, both as a recessive or as a dominant one. Also there are 13 patients in our sample who bear neither Arginine 52 alpha DQ nor non-Aspartate 57 beta DQ susceptibility factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed2003

[Anterior knee pain in children and adolescents. Diagnosis and conservative treatment].

Anterior knee pain is a common problem in childhood and adolescence with a prevalence of 4-30% in regional surveys. Although different etiologic theories are discussed in a large number of published studies, most cases are probably attributed to lower extremity malalignment, muscular imbalance, or physical overactivity (or even a combination of all three). Thorough clinical investigation should result in a definition of relevant static or functional problems as underlying causes of the disease. Radiographic analysis is mainly performed to exclude severe pathology (i.e., malignancies), as the correlation between described morphometric variables and clinical problems is weak. Prior to therapeutic recommendations, the benign natural course of the disease should be discussed with patients and their parents. In a large number of published studies with different conservative treatment protocols, positive results for many regimens are reported. The size,however, is not always large enough to prove superior outcome when compared to the natural course of the disease. There is also no evidence to support the superiority of one physiotherapy intervention over others.

Adolescent↗
PubMed1987

Dichloroacetate derivatives. Metabolic effects and pharmacodynamics in normal rats.

Dichloroacetate (DCA) reduces blood glucose, lactate and lipids in diabetes or during fasting. Chronic use of DCA, however, is limited by toxicity, probably due in part to its rapid conversion to oxalate in vivo. In theory, therefore, DCA's efficacy may be retained and its toxicity minimized by controlling its rate of metabolism. We attempted to alter DCA pharmacokinetics and bioavailability by synthesizing various derivatives comprising DCA esters with polyols and DCA ionic complexes. Twenty-four hour fasted, nondiabetic rats received single, orogastric doses of saline (control) sodium DCA (100mg/kg) or the following derivatives (D1-4): the esters D1-D3: potassium tetra (dichloroacetyl) glucuronate (D1), inositol-monophosphate-tetradichloroacetate (D2), inositol-hexadichloroacetate (D3) and inositol-hexa [N-methylnicotinate] hexadichloroacetate salt (D4). Each derivative was administered at a dose that would ultimately provide 100 mg/kg DCA as the anion. All derivatives were orally effective in significantly decreasing blood glucose and lactate. D4 exerted the most potent and long-lasting glucose- and lactate-lowering effects, yet increased plasma DCA concentrations less than an equivalent dose of the sodium salt. When administered to reverse light-cycled rats, D4 markedly inhibited the incorporation of tritiated water into cholesterol and triglycerides. We conclude that derivatives of DCA retain the biological activity of the parent compound, but may exhibit different pharmacokinetics. They may eventually prove useful in the treatment of diabetes mellitus, hyperlipidemia and lactic acidosis in man.

Acetates↗
PubMed1993

Target detection in left and right hemispace: effects of positional pre-cuing and type of background.

The two experiments reported here examined the degree to which detection of targets by the right hemisphere can be characterized as occurring at the global level and detection by the left hemisphere can be characterized as occurring at the local level. Although the results provided some evidence for such a dichotomy, these hemispheric differences in processing were modified by the overall configuration in which the item is embedded, the nature of the background, and whether a precue indicates the probable location of the target. The findings are discussed in relation to current theories of hemispheric differences in spatial processing.

Adolescent↗
PubMed1985

Alcohol increases cigarette smoking: a laboratory demonstration.

Most people would agree that a relationship exists between drinking alcohol and smoking cigarettes, but there is very little empirical evidence demonstrating a direct causal association. Study of the relationship has been hampered by the lack of a simple laboratory methodology. This article describes an efficient experimental paradigm. Fourteen male narcotic addicts in methadone maintenance treatment volunteered to come to the laboratory for two smoking sessions, during which each subject was given either an alcoholic drink or orange juice, followed by three cigarettes at 20-minute intervals. Drinking alcohol significantly increased the amount and rate of smoking. However, not all subjects reacted to alcohol with increased smoking, and we were unable to account for those individual differences. Our finding supports the theory that a direct causal mechanism linking smoking and drinking exists. That link probably has clinical significance, because there is evidence that ex-smokers are at particularly high risk when they drink alcohol.

Adult↗
PubMed2001

Non-equilibrium proteins.

There exist no methodical studies concerning non-equilibrium systems in cellular biology. This paper is an attempt to partially fill this shortcoming. We have undertaken an extensive data-mining operation in the existing scientific literature to find scattered information about non-equilibrium subcellular systems, in particular concerning fast proteins, i.e. those with short turnover half-time. We have advanced the hypothesis that functionality in fast proteins emerges as a consequence of their intrinsic physical instability that arises due to conformational strains resulting from co-translational folding (the interdependence between chain elongation and chain folding during biosynthesis on ribosomes). Such intrinsic physical instability, a kind of conformon (Klonowski-Klonowska conformon, according to Ji, (Molecular Theories of Cell Life and Death, Rutgers University Press, New Brunswick, 1991)) is probably the most important feature determining functionality and timing in these proteins. If our hypothesis is true, the turnover half-time of fast proteins should be positively correlated with their molecular weight, and some experimental results (Ames et al., J. Neurochem. 35 (1980) 131) indeed demonstrated such a correlation. Once the native structure (and function) of a fast protein macromolecule is lost, it may not be recovered--denaturation of such proteins will always be irreversible; therefore, we searched for information on irreversible denaturation. Only simulation and modeling of protein co-translational folding may answer the questions concerning fast proteins (Ruggiero and Sacile, Med. Biol. Eng. Comp. 37 (Suppl. 1) (1999) 363). Non-equilibrium structures may also be built up of protein subunits, even if each one taken by itself is in thermodynamic equilibrium (oligomeric proteins; sub-cellular sol-gel dissipative network structures).

Amino Acid Sequence↗
PubMed2002

Chaperones and aging: role in neurodegeneration and in other civilizational diseases.

Chaperones are highly conserved proteins responsible for the preservation and repair of the correct conformation of cellular macromolecules, such as proteins, RNAs, etc. Environmental stress leads to chaperone (heat-shock protein, stress protein) induction reflecting the protective role of chaperones as a key factor for cell survival and in repairing cellular damage after stress. The present review summarizes our current knowledge about the chaperone-deficiency in the aging process, as well as the possible involvement of chaperones in neurodegenerative diseases, such as in Alzheimer's, Parkinson's, Huntington- and prion-related diseases. We also summarize a recent theory implying chaperones as "buffers" of variations in the human genome, which role probably increased during the last 200 years of successful medical practice minimizing natural selection. Chaperone-buffered, silent mutations may be activated during the aging process, which leads to the phenotypic exposure of previously hidden features and might contribute to the onset of polygenic diseases, such as atherosclerosis, cancer, diabetes and several neurodegenerative diseases.

Aging↗
PubMed2004

Influence of altitude and age in the accumulation of organochlorine compounds in fish from high mountain lakes.

The analysis of hexachlorobenzene, hexachlorocyclohexanes, polychlorobiphenyls, and DDTs in muscle of fish from high mountain lakes shows that a proportion of their concentration variance depends on fish age and lake altitude. Interestingly, the magnitude of this share corresponds linearly with the log-transformed vapor pressure (Vp) of the organochlorine compounds (OC). Thus, the distributions of OC with Vp < 10(-2.5) Pa are mostly determined by these two variables. Altitude gradients mainly respond to temperature differences, involving concentration increases of 25-150 times between 8.7 and -2.3 degrees C. The age effect encompasses concentration increments of 2.4-7.8 for average lake differences between 2 and 13 yr. However, both effects are independent since no correlation between fish age and lake altitude is observed. Fish liver concentrations exhibit the same pattern, but the correlations are only significantfor age, suggesting thatthe temperature trend is more related to long-term accumulation than episodic intake. The temperature effect is independent from compound origin. In addition, the sites situated at highest altitude, those most distant from possible ground pollution sources, are the most polluted. The results can be explained by condensation effects such as those described for the latitudinal trends that support the global distillation theory. However, in the high altitude lakes a temperature-dependent amplification mechanism, probably related to low metabolism and respiration at lowtemperatures, enhances OC accumulation in fish beyond the increases predicted from theoretical condensation and solubilization enthalpies. The observed temperature dependence suggests that a general remobilization of OC accumulated in high mountain areas could take place as a consequence of the general warming of these areas anticipated in the climatic change studies.

Adaptation, Physiological↗
PubMed2003

Antioxidant activity of bakuchiol: experimental evidences and theoretical treatments on the possible involvement of the terpenoid chain.

The protective activity of the plant-derived meroterpene, bakuchiol [1-(4-hydroxyphenyl)-3,7-dimethyl-3-vinyl-1,6-octadiene, 1], against oxidative damages to lipids and proteins has been investigated and rationalized based on the scavenging activity of 1 against various oxidizing radicals (Cl(3)CO(2)(*), linoleic acid peroxyl radicals, LOO(*), DPPH radicals, (*)OH, and glutathiyl radicals). The rate constants of the scavenging reactions, transients formed in these reactions, and their mechanistic pathways have been probed using optical pulse radiolysis technique. Besides 1, its methyl ether derivative 2 also could prevent lipid peroxidation in rat brain homogenate, indicating the probable participation of their terpenoid chains in scavenging LOO(*). This was further corroborated from the pulse radiolytic studies on the reaction between the glutathiyl radicals and the compounds 1 and 2 as well as two other congeners, 3 and 4, which showed transient absorptions at approximately 300 nm attributable to some C-centered allylic radicals. On the basis of the strong signals at approximately 300 nm with 1-3 as compared to compound 4, formation of the allylic radical adjacent to the trisubstituted olefin function in 1-3 was envisaged. This was confirmed by quantum chemical calculations of the relative energies of the probable radical species derivable from 2 using Hartree-Fock and density functional theory along with self-consistent reaction field model. In the case of 1, the allylic radical was found to be transformed into the phenoxyl radical at a later stage. All of these data revealed, for the first time, the importance of the terpenoid moiety of bakuchiol in controlling its antioxidant action via radical scavenging.

Animals↗
PubMed1997

Total charge movement per channel. The relation between gating charge displacement and the voltage sensitivity of activation.

One measure of the voltage dependence of ion channel conductance is the amount of gating charge that moves during activation and vice versa. The limiting slope method, introduced by Almers (Almers, W. 1978. Rev. Physiol. Biochem. Pharmacol. 82:96-190), exploits the relationship of charge movement and voltage sensitivity, yielding a lower limit to the range of single channel gating charge displacement. In practice, the technique is plagued by low experimental resolution due to the requirement that the logarithmic voltage sensitivity of activation be measured at very low probabilities of opening. In addition, the linear sequential models to which the original theory was restricted needed to be expanded to accommodate the complexity of mechanisms available for the activation of channels. In this communication, we refine the theory by developing a relationship between the mean activation charge displacement (a measure of the voltage sensitivity of activation) and the gating charge displacement (the integral of gating current). We demonstrate that recording the equilibrium gating charge displacement as an adjunct to the limiting slope technique greatly improves accuracy under conditions where the plots of mean activation charge displacement and gross gating charge displacement versus voltage can be superimposed. We explore this relationship for a wide variety of channel models, which include those having a continuous density of states, nonsequential activation pathways, and subconductance states. We introduce new criteria for the appropriate use of the limiting slope procedure and provide a practical example of the theory applied to low resolution simulation data.

Electrophysiology↗