From a homeostatic to a homeodynamic self

Life as an autonomous homeostatic system is discussed. A mechanism that drives a homeostatic state to an autonomous self-moving state is examined with two computational cell models. The mechanism is met with Ashby's ultrastability, where random parameter searching is activated when a system breaks a viability constraint. Such a random search process is replaced by the membrane shape in the first model and by chaotic population dynamics in the second model. Emergence of sensors, motors and the recursive coupling between them is shown to be a natural outcome of an autonomous homeostatic system.     

Testing a Primary and a Secondary Endpoint in a Group Sequential Design

Summary We consider a clinical trial with a primary and a secondary endpoint where the secondary endpoint is tested only if the primary endpoint is significant. The trial uses a group sequential procedure with two stages. The familywise error rate (FWER) of falsely concluding significance on either endpoint is to be controlled at a nominal level α. The type I error rate for the primary endpoint is controlled by choosing any α‐level stopping boundary, e.g., the standard O'Brien–Fleming or the Pocock boundary. Given any particular α‐level boundary for the primary endpoint, we study the problem of determining the boundary for the secondary endpoint to control the FWER. We study this FWER analytically and numerically and find that it is maximized when the correlation coefficient ρ between the two endpoints equals 1. For the four combinations consisting of O'Brien–Fleming and Pocock boundaries for the primary and secondary endpoints, the critical constants required to control the FWER are computed for different values of ρ. An ad hoc boundary is proposed for the secondary endpoint to address a practical concern that may be at issue in some applications. Numerical studies indicate that the O'Brien–Fleming boundary for the primary endpoint and the Pocock boundary for the secondary endpoint generally gives the best primary as well as secondary power performance. The Pocock boundary may be replaced by the ad hoc boundary for the secondary endpoint with a very little loss of secondary power if the practical concern is at issue. A clinical trial example is given to illustrate the methods.     

Conversion of a transmembrane to a water-soluble protein complex by a single point mutation

Proteins exist in one of two generally incompatible states: either membrane associated or soluble. Pore-forming proteins are exceptional because they are synthesized as a water-soluble molecule but end up being located in the membrane -- that is, they are nonconstitutive membrane proteins. Here we report the pronounced effect of the single point mutation Y221G of the pore-forming toxin aerolysin. This mutation blocks the hemolytic activity of the toxin but does not affect its initial structure, its ability to bind to cell-surface receptors or its capacity to form heptamers, which constitute the channel-forming unit. The overall structure of the Y221G protein as analyzed by cryo-negative staining EM and three-dimensional reconstruction is remarkably similar to that of the wild type heptamer. The mutant protein forms a mushroom-shaped complex whose stem domain is thought to be within the membrane in the wild type toxin. In contrast to the wild type heptamer, which is a hydrophobic complex, the Y221G heptamer is fully hydrophilic. This point mutation has, therefore, converted a normally membrane-embedded toxin into a soluble complex.     

Towards a definition of a crop wild relative

Crop wild relatives are an important socio-economic resource that is currently being eroded or even extinguished through careless human activities. If the Conference of the Parties (COP) to the CBD 2010 Biodiversity Target of achieving a significant reduction in the current rate of loss is to be achieved, we must first define what crop wild relatives are and how their conservation might be prioritised. A definition of a crop wild relative is proposed and illustrated in the light of previous Gene Pool concept theory. Where crossing and genetic diversity information is unavailable, the Taxon Group concept is introduced to assist recognition of the degree of crop wild relative relatedness by using the existing taxonomic hierarchy.     

Genetic Structure of a Population Occupying a Circular Habitat

The geographical structure of a finite population distributed continuously and homogeneously along a circular habit is explored. Selection is supposed to be absent, and the analysis is restricted to a single locus with discrete, non-overlapping generations. Assuming every mutant is new to the population, the rate of decay of genetic variability is obtained, and the probability that two homologous genes separated by a given distance are different alleles is calculated. If moments of the migration function higher than second are neglected, the eigenvalue equation is shown to be a simple trigonometric one, and the Fourier series giving the transient and stationary probabilities of allelism are summed in terms of elementary functions. The proportion of homozygotes, the effective number of alleles maintained in the population, and the amount of local differentiation of gene frequencies are discussed.     

Stability of a melittin pore in a lipid bilayer: a molecular dynamics study

We have investigated the configuration and the stability of a single membrane pore bound by four melittin molecules and embedded in a fully hydrated bilayer lipid membrane. We used molecular dynamics simulations up to 5.8 ns. It is found that the initial tetrameric configuration decays with increasing time into a stable trimer and one monomer. This continuous transformation is accompanied by a lateral expansion of the aqueous pore exhibiting a final size comparable to experimental findings. The expansion-induced formation of an interface between the pore-lining acyl chains of the lipids and the pore water ("hydrophobic pore") is transformed into an energetically more favorable toroidal pore structure where some lipid heads are translocated from the rim to the central part of the interface ("hydrophilic pore"). The expansion of the pore is supported by the electrostatic repulsion among the alpha-helices. It is hypothesized that pore growth, and hence cell lysis, is induced by a melittin-mediated line tension of the pore.     

On a stochastic version of a modified Nicholson-Baily model

‘Deterministic’ models in population dynamics often are really approximations to stochastic models, justified by an appeal to ‘the law of large numbers’. It is proposed to call such models ‘pseudodeterministic’. Four questions are discussed in this article: (1) What errors may be made by equating deterministically predicted values to expectations? (2) When, and in what sense, may numbers be assumed to be large? (3) How large are the variances, coefficients of variations, etc., as assigned to the variables in the stochastic versions of the models? (4) What role may pseudodeterministic models play in empirical research, where problems of statistical reliability arise? As an example, a modified Nicholson-Bailey model of the interaction between insect parasitoids and their hosts is discussed; the modification consists of assigning a random (density-independent) mortality to the parasitoid population. A stochastic version of this model is discussed. The expectation of the final host density is compared with the value computed from the deterministic model. The latter value is systematically lower than the former. The magnitude of the difference depends on parameter values. The variability to be expected with the stochastic model is characterized by the coefficient of variation of the final host density; its dependence on parameter values and initial conditions is discussed. It is concluded that it is worthwhile in practical applications to estimate parasitoid mortality, and that the coefficient of variation in real situations may be far from negligible.     

Race-centrism: a critique and a research agenda

This article reviews some of the most prominent books in the field of race studies in the USA and identifies their shared assumptions: that racial inequality is the primary principle of stratification in the USA; that is has transformed but not lessened since the civil rights era; that it can be explained by the racist inclinations of the white majority, which operates as a collective, strategic actor to preserve its dominance; and finally, that racial domination plays a similarly crucial role around the world. I explore what kind of questions would need to be answered in order to put these assumptions on firmer empirical and theoretical ground and outline a corresponding research agenda. Some empirical evidence is provided to question the assumption that race plays a dominant role around the world and is associated with more political inequality than ethnic divisions.     

Flavohemoglobin, a globin with a peroxidase-like catalytic site

Biochemical studies of flavohemoglobin (Hmp) from Escherichia coli suggest that instead of aerobic oxygen delivery, a dioxygenase converts NO to NO3(-) and anaerobically, an NO reductase converts NO to N(2)O. To investigate the structural features underlying the chemical reactivity of Hmp, we have measured the resonance Raman spectra of the ligand-free ferric and ferrous protein and the CO derivatives of the ferrous protein. At neutral pH, the ferric protein has a five-coordinate high-spin heme, similar to peroxidases. In the ferrous protein, a strong iron-histidine stretching mode is present at 244 cm(-1). This frequency is much higher than that of any other globin discovered to date, although it is comparable to those of peroxidases, suggesting that the proximal histidine has imidazolate character. In the CO derivative, an open and a closed conformation were detected. The distal environment of the closed conformation is very polar, where the heme-bound CO strongly interacts with the B10 Tyr and/or the E7 Gln. These data demonstrate that the active site structure of Hmp is very similar to that of peroxidases and is tailored to perform oxygen chemistry.     

Matrix metalloproteinases: a tail of a frog that became a prince

It is 40 years since the first member of what came to be known as the matrix metalloproteinase (MMP) family was described. Structural, molecular and biochemical approaches have subsequently contributed to piecing together the puzzle of how MMPs work, and how they contribute to various disease processes.     

Decay instability of a laser pulse propagating in a transverse direction in a magnetized plasma

The decay instability of a lser pulse propagating across an external magnetic field in a subscritical plasma is investigated analytically and numerically. It is shown that, when the relaxation of the pulse is taken into account, the hydrodynamic growth rate of the decay instability is slower than that obtained earlier in the constant-amplitude pump wave approximation. The results of numerical simulations by a particle-in-cell method demonstrate that an increase in the amplitude of the parametrically excited waves is accompanied by a decrease in their group velocity; in this case, up to 85% of the laser energy is converted into the energy of the plasma particles. It is found that, under resonance conditions, the magnetic field acts to increase the energy of the accelerated ions that escape from the plasma slab through its front boundary.     

Antagonistic coevolution between a bacterium and a bacteriophage

Antagonistic coevolution between hosts and parasites is believed to play a pivotal role in host and parasite population dynamics, the evolutionary maintenance of sex and the evolution of parasite virulence. Furthermore, antagonistic coevolution is believed to be responsible for rapid differentiation of both hosts and parasites between geographically structured populations. Yet empirical evidence for host-parasite antagonistic coevolution, and its impact on between-population genetic divergence, is limited. Here we demonstrate a long-term arms race between the infectivity of a viral parasite (bacteriophage; phage) and the resistance of its bacterial host. Coevolution was largely driven by directional selection, with hosts becoming resistant to a wider range of parasite genotypes and parasites infective to a wider range of host genotypes. Coevolution followed divergent trajectories between replicate communities despite establishment with isogenic bacteria and phage, and resulted in bacteria adapted to their own, compared with other, phage populations.     

Vegetation as a component of a non-nested hierarchy: a conceptual model

Abstract. A general conceptual model of vegetation based on hierarchy theory is presented. The model emphasizes that prediction of vegetation requires consideration of both mechanisms of vegetation change and the constraints within which it occurs. The mechanisms of vegetation change are the responses to and effects upon their surroundings of individual plants. The most general constraints upon vegetation are aspects of the environment not affected by vegetation over successional time, and the pool of species within dispersal range. Examples of such environmental factors include macroclimate and soil parent material. In some cases, vegetation may alter important labile environmental factors such as soil nutrient and water availability. Some vegetation compositions appear to be resistant to changes in the general constraints. Due to both sources, there are multiple possible vegetation compositions given the same general constraints. Disturbance is defined as an abrupt change in the constraints on the vegetation resulting in a change in the vegetation's state or dynamics. Both the recognition of disturbance and the distinction between independent and labile environmental factors depend on the spatial and temporal scale of observation. For example, a particular wildfire at a given stand may be a disturbance, whereas at a larger scale of observation the same event may contribute to the wildfire regime, part of the constraints at that scale. Similarly, levels of soil organic matter may constrain vegetation over short time scales, due to influencing availability of water and nutrients. Over long time scales, the vegetation itself is a primary determinant of soil organic matter content. This model contains elements of both the initial, holistic theory of vegetation and recent, reductionistic approaches. It reiterates the need to considerboth mechanisms and constraints, stressed by contemporary and earlier workers. Hierarchy theory provides new insights concerning sufficient conditions for prediction, possible limits on predictability, and appropriate research strategy.     

Eo: a history of a mutation

Eighteen mouse t haplotype-carrying strains were found not to express cell-surface E molecules controlled by class II genes of the H-2 complex (= Eo strains). Northern and Southern blot analysis of these and other, non-t strains that also fail to express the E molecule, has revealed two kinds of defect. Three strains (CRO437, tw2, and presumably to) were found to transcribe the E alpha gene, but they were not able to convert the message into a functional protein. All other Eo strains fail to transcribe the E alpha gene because of a deletion encompassing the promoter region, the RNA initiation site, and the first exon. The length of the deletion is approximately 650 +/- 50 bp. These two defects closely resemble those found previously in standard inbred strains carrying the H-2f, H-2q (failure of E mRNA to be expressed functionally), H-2b, and H-2s (deletion of a part of the E alpha gene) haplotypes. In particular, the location and length of the E alpha deletion appear to be the same in the strains carrying this mutation. The E alpha deletion is in linkage disequilibrium with certain alleles at other H-2 loci in some of the strains. These observations, combined with the growing evidence that H-2 haplotypes associated with t chromosomes derive from a single ancestral haplotype, suggest that the E alpha deletion is an old mutation and that it has been disseminated in mouse populations by the t chromosomes.     

Ending a decade of deception: a valiant failure, a not-so-valiant failure, and a success story

Prior studies involving two methods, Brooks Parsimony Analysis (BPA) and TreeMap, have found BPA to be the more reliable method. Recent criticisms leveled at these studies argue that the tests were unfairly created and biased in favor of BPA. The authors of a recent critique offered new exemplars to demonstrate flaws in BPA, plus a simple fix to correct the flaws found in TreeMap. A re‐evaluation of their exemplars clearly shows that the authors' calculations are incorrect, their understanding of the methods is lacking, and that their simple fix does not work. Additional analyses using TreeMap 2.02 are run to show that TreeMap 2.02, like TreeMap 1.0, cannot adequately deal with widespread parasites, contrary to the claims of its supporters. Furthermore, the exemplars corroborate previous findings that BPA, when calculated correctly, is more reliable than TreeMap1.0 and TreeMap 2.02 and therefore the method of choice in coevolutionary and biogeographic studies.     

Homeostasis: a plea for a unified approach

Accompanying the progressive erosion of a coherent sense of physiology as an intellectual discipline, there has been a tendency to lose sight of the homeostatic principles that underpin physiological science, and to teach them in an oversimplified form. When (as is increasingly the case) these principles are rediscovered, they are often treated as something both novel and distinct from homeostasis, fragmenting what is best understood and taught as a unified whole. This article urges a more unitary approach to homeostasis, and attempts to show how such an approach can be presented.     

Derivation of a Floquet Formalism within a Natural Framework

Many biological systems experience a periodic environment. Floquet theory is a mathematical tool to deal with such time periodic systems. It is not often applied in biology, because linkage between the mathematics and the biology is not available. To create this linkage, we derive the Floquet theory for natural systems. We construct a framework, where the rotation of the Earth is causing the periodicity. Within this framework the angular momentum operator is introduced to describe the Earth’s rotation. The Fourier operators and the Fourier states are defined to link the rotation to the biological system. Using these operators, the biological system can be transformed into a rotating frame in which the environment becomes static. In this rotating frame the Floquet solution can be derived. Two examples demonstrate how to apply this natural framework.     

Evaluating polygraphy from a psychophysiological perspective: a specific-effects analysis

It is suggested that purportedly scientific positions and technologies are actually spiritualistic or superstitious to the extent that specific effects are not identified and evaluated. This claim is then examined with respect to polygraphy, which appears to have particularly strong spiritualistic tendencies. This technology's putative basis is the science of psychophysiology, which is the study of psychological processes by means of unobtrusive physiological measures that reflect functions over which there is relatively little voluntary control. The underlying rationale of polygraphy is that information about these functions provided to the examiner has a specific, beneficial effect of improving the detection of deception. Before considering the validity of the polygraph in these specific-effect terms, the paper notes some serious societal problems involved in the use of the polygraph, problems that suggest that polygraphy is appropriately characterized as a serious "social disease". As to its scientific status, the technique suffers from at least three significant and possibly insurmountable problems: 1) the records are not read "blind"; 2) the method of scoring is subjective, compared to the standards of scientific psychophysiology; and 3) the so-called "control" question method does not involve control in the standard, accepted, scientific sense of that term. However, much of the rest of psychology is also criticised as teleological and spiritualistic, and it is suggested that the polygraph is merely a dramatic illustration of the spiritualist approach that permeates the thought of most researchers in, and practitioners of, the science of psychology.     

Baggasse preservation: a need for a biotechnological approach

Paper is one of the basic needs of modern life. With the consumption of paper likely to grow to 320 million MT by the year 2001, the the worldwide pulp and paper industry is gradually realizing that there is a shortage of the traditional raw material of cellulosic fiber. Bagasse--a byproduct of the sugar industry, presents a potential source of fiber for the paper industry without further compromising the environmental concern. It is cheap, perennially replenishible, presently does not have an alternative economically attractive value added usage, and has adequate chemical and mechanical properties for paper making. However, for it to be available to the paper industry throughout the year, it needs to be stored and preserved for a period of 6 to 8 months. With inherent problems associated with bagasse morphology, intricacies reflected as a result of its physicochemical characteristics, army of microbial infestants, cost-effective quality expectations of the paper industry, and the ecofriendly approach demanded by the society/pollution control boards/environmentalists, there does not seem to be any viable alternative except to use biotechnology approaches for bagasse preservation. It envisages the preservation of maximally depithed bagasse in the piles/heaps, using one-time fine misting of a preservative formulation comprised of biodegradable and nondegradable chemicals inhibiting the microbial population at selected enzyme levels. Its efficacy is improved by open, dry, windy, and moderate sunlit sites for storage. The method is simple, sustainable, and superior to the prevalent methods that are cost, capital, and energy intensive, non-eco-friendly and have adverse cost:benefit ratios. The biotechnology approach has an inherent scope for further optimization, automation, and economization.