Journeying Between Desire and Anthropology: A Story in Suspense

Anthropology is a discipline based on the motif of the journey and ‘the myth of the eternal return’. This is the journey out to the ‘other’in order to return to constitute ‘self, and this movement is a movement of desire. The desire is for wholeness, for self‐presence, for a unified self. It is a desire for origins. And this desire is evident in anthropological practices as it is in myths and fairytales—all tell stories that speak of the desire for a separate, an original, self. Yet ‘the myth of the eternal return’reveals that the enactment of the story is itself originating. The origin is not a thing to be hunted down and appropriated—it is no thing. Like the archetypes which flow through stories, it is alive in the telling. The story I tell in this paper is about my own desires. It speaks of the desire to undergo the rite of passage of anthropology, and of how this journey was interrupted by the anthropologist who always journeys before me. And yet. it is through the inextricable relations with the writings of the “other‘ anthropologist that alluring moments of different desiring are fleetingly revealed. In the end. my relations with anthropology tell of a paradox: of the desire for a transcendental journey in order to constitute self and the seductive desire for immersion—to lose self, the story remains in suspense.     

Application of macroscopic principles to microbial metabolism

General expressions for mass, elemental, energy, and entropy balances are derived and applied to microbial growth and product formation. The state of the art of the application of elemental balances to aerobic and heterotrophic growth is reviewed and extended somewhat to include the majority of the cases commonly encountered in biotechnology. The degree of reduction concept is extended to include nitrogen sources other than ammonia. The relationship between a number of accepted measures for the comparison of substrate yields is investigated. The theory is illustrated using a generalized correlation for oxygen yield data. The stoichiometry of anaerobic product formation is briefly treated, a limit to the maximum carbon conservation in product is derived, using the concept of elemental balance. In the treatment of growth energetics the correct statement of the second law of thermodynamics for growing organisms is emphasized. For aerobic heterotrophic growth the concept of thermodynamic efficiency is used to formulate a limit the substrate yield can never surpass. It is combined with a limit due to the fact that the maximum carbon conservation in biomass can obviously never surpass unity. It is shown that growth on substrates of a low degree of reduction is energy limited, for substrates of a high degree of reduction carbon limitation takes over. Based on a literature review concerning yield data some semiempirical notions useful for a preliminary evolution of aerobic heterotrophic growth are developed. The thermodynamic efficiency definition is completed by two other efficiency measures, which allow derivation of simple equations for oxygen consumption and heat production. The range of validity of the constancy of the rate of heat production to the rate of oxygen consumption is analyzed using these efficiency measures. The energetic of anaerobic growth are treated—it is shown that an approximate analysis in terms of an enthalpy balance is not valid for this case, the evaluation of the efficiency of growth has to be based on Gibbs free energy changes. A preliminary analysis shows the existence of regularities concerning the free energy conservation on anaerobic growth. The treatment is extended to include the effect of growth rate by the introduction of a linear relationship for substrate consumption. Aerobic and anaerobic growth are discussed using this relationship. A correlation useful in judging the potentialities for improvement in anaerobic product formation processes is derived. Finally the relevance of macroscopic principles to the modeling of bioengineering systems is discussed.     

Gene Genealogies within Mutant Allelic Classes

A coalescent theory of the gene genealogy within an allelic class that arises by a unique mutational event is developed and analyzed. To interpret this theory it was necessary to expand on existing theory for populations of varying size. Two features of the gene genealogy--the average pairwise distance and the total tree length--within the mutant class and within the nonmutant class are found. An index, I, is proposed that describes the extent to which a genealogy is similar to one from a population of constant size (for which I = 0) or to a star genealogy (for which I = 1). The value of I is positive in growing populations and is generally positive for the gene genealogy for the mutant class. The value of I is negative for a population decreasing in size and for the nonmutant class, if the mutant arose recently. The results are discussed in the context of the infinite sites model of mutation, which is appropriate for nucleotide sequence data, and the generalized stepwise mutation model, which is appropriate for microsatellite loci. The same genealogical methods are used to find the probability of at least one recombination event between a nucleotide that defines an allelic class and a marker at a nearby linked site.     

Visualising and assessing the probable error from downscaling ecological time series data

Collecting natural data at regular, fine scales is an onerous and often costly procedure. However, there is a basic need for fine scale data when applying inductive methods such as neural networks or genetic algorithms for the development of ecological models. This paper will address the issues involved in interpolating data for use in machine learning methods by considering how to determine if a downscaling of the data is valid. The approach is based on a multi-scale estimate of errors. The resulting function has similar properties to a time series variogram; however, the comparison at different scales is based on the variance introduced by rescaling from the original sequence. This approach has a number of properties, including the ability to detect frequencies in the data below the current sampling rate, an estimate of the probable average error introduced when a sampled variable is downscaled and a method for visualising the sequences of a time series that are most susceptible to error due to sampling. The described approach is ideal for supporting the ongoing sampling of ecological data and as a tool for assessing the impact of using interpolated data for building inductive models of ecological response.     

Mass Ligand Binding Screening for Receptor Antagonists: Prototype New Drugs and Blind Alleys

Abstract

The ligand binding assay is a powerful tool in the search for antagonists for novel receptors, and for identification of novel classes of antagonists for well-known receptors. Ligand binding mass screening can be adapted for very high throughput. In order for mass screening to be useful, it is necessary to strictly define the binding characteristics for a compound to be considered a putative receptor antagonist. In practice, we have found that synthetic pursuit of a compound with a K_i of ± 1 uM is likely to lead down a blind alley unless very good evidence for specificity is available. Even potent competitors for binding should be thoroughly evaluated in assays of biological activity before a synthetic program is initiated in earnest.     

Minimum shear wind strength required for dynamic soaring of albatrosses

The transfer of energy from the moving air in the shear wind above the sea surface to a bird is considered as an energy source for dynamic soaring, with the goal to determine the minimum shear wind strength required for the dynamic soaring of albatrosses. Focus is on energy-neutral trajectories, implying that the energy gain from the moving air is just sufficient to compensate for the energy loss due to drag for a dynamic soaring cycle. A mathematical optimization method is used for computing minimum shear wind energy-neutral trajectories, using a realistic flight mechanics model for the soaring of albatrosses. Thus, the minimum shear wind strength required for dynamic soaring is determined. The minimum shear wind strength is of a magnitude that often exists or is exceeded in areas in which albatrosses are found. This result holds for two control cases dealt with, one of which shows a freely selectable and the other a constant lift coefficient characteristic. The mechanism of energy transfer from the shear flow to the bird is considered, and it is shown that there is a significant energy gain in the upper curve and a loss in the lower curve. As a result, the upper curve can be qualified as the characteristic flight phase of dynamic soaring to achieve an energy gain.     

Prediction of signal peptides using scaled window

Cells use a ZIP code system to sort newly synthesized proteins and deliver them wherever they are needed: into different internal compartments called organelles or even out of the cell altogether. One of the most essential features of the ZIP code system is the signal sequence or “address tag,” which is originally present in the N-terminal part of the protein and is trimmed away by the time it is secreted. Owing to the importance of signal peptides for understanding the molecular mechanisms of genetic diseases, reprogramming cells for gene therapy, and constructing new drugs for correcting a specific defect, it is highly desirable to develop a fast and accurate method to identify the signal peptides. In this paper, a scaled window model is proposed. Based on such a model as well as Markov chain theory, a new algorithm is formulated for predicting the signal peptides. Test results for the 1939 secretory proteins and 1440 non-secretary proteins have indicated that the new algorithm is particularly successful in the overall success rate, and hence can serve as a complementary tool to the existing algorithms for signal peptide prediction.     

Duncan's k-ratio Bayes rule approach to multiple comparisons: an overview

An alternative to frequentist approaches to multiple comparisons is Duncan's k-ratio Bayes rule approach. The purpose of this paper is to compile key results on k-ratio Bayes rules for a number of multiple comparison problems that heretofore, have only been available in separate papers or doctoral dissertations. Among other problems, multiple comparisons for means in one-way, two-way, and treatments-vs.-control structures will be reviewed. In the k-ratio approach, the optimal joint rule for a multiple comparisons problem is derived under the assumptions of additive losses and prior exchangeability for the component comparisons. In the component loss function for a comparison, a balance is achieved between the decision losses due to Type I and Type II errors by assuming that their ratio is k. The component loss is also linear in the magnitude of the error. Under the assumption of additive losses, the joint Bayes rule for the component comparisons applies to each comparison the Bayes test for that comparison considered alone. That is, a comparisonwise approach is optimal. However, under prior exchangeability of the comparisons, the component test critical regions adapt to omnibus patterns in the data. For example, for a balanced one-way array of normally distributed means, the Bayes critical t value for a difference between means is inversely related to the F ratio measuring heterogeneity among the means, resembling a continuous version of Fisher's F-protected least significant difference rule. For more complicated treatment structures, the Bayes critical t value for a difference depends intuitively on multiple F ratios and marginal difference(s) (if applicable), such that the critical t value warranted for the difference can range from being as conservative as that given by a familywise rule to actually being anti-conservative relative to that given by the unadjusted 5%-level Student's t test.     

Regulatory Issues for Genetic Testing in Clinical Practice

Whereas deliver of health care is nationally based with great differences in ways of service provision and financing between countries, and thus not subject to international regulations, genetic testing has become more exposed to international regulations and conventions. This is due to an interest of protecting the individual for abuse by inappropriate use of genetic information, but also to the fact that a specimen from a person aimed for a medical (clinical genetic) test is considered as "tradable goods", and thus also subject to other non-medical associated regulations. There is a substantial transborder flow of samples for genetic testing thus requiring internationally accepted quality standards. Therefore, laboratories acting on an international market need to follow certain rules and regulations, also applicable to obtain high-quality standards nationally. Further, genetic testing for rare disorders is often provided by a limited number of non-commercial laboratories and associated with research programs for the individual disorders. International surveys have revealed that there is a general lack of high standards for quality assurance. This article is aimed to give an introduction and overview of regulations, conventions, and quality standards applicable for the laboratory who is seeking to improve there quality performance.     

Responsibility amid the social determinants of health

It is natural to think that there is a tight connection between whether someone is responsible for some outcome and whether it is appropriate to hold her accountable for that outcome. And this natural thought naturally extends to health: if someone is responsible for her health, then, all else being equal, she is accountable for it. Given this, some have thought that responsibility for health has an important role to play in distributing the benefits and burdens of healthcare. But there is a reason for caution. That health is influenced by social, economic, and environmental factors is a matter of consensus. And some have argued that in light of these social determinants of health, individuals are not typically responsible for their health, rendering inappropriate policies that employ a responsibility‐for‐health criterion. This debate implicates a number of overlapping concepts and questions that are often difficult to pull apart. And I worry that those who maintain that social determinants undermine responsibility for health have latched on to the wrong target. The social determinants of health are relevant to such policies, but, I argue, not by globally undermining responsibility. Rather, social determinants are sometimes responsibility‐undermining, sometimes responsibility‐preserving, and often relevant to whether we should hold individuals accountable for their health regardless of their responsibility. This calls for a more nuanced appraisal of the ways in which the social determinants of health are relevant to such policies. And here I attempt to provide one.     

The impact of climate change on birds

Weather is of major importance for the population dynamics of birds, but the implications of climate change have only recently begun to be addressed. There is already compelling evidence that birds have been affected by recent climate changes. This review suggests that although there is a substantial body of evidence for changes in the phenology of birds, particularly of the timing of migration and of nesting, the consequences of these responses for a species' population dynamics is still an area requiring in-depth research. The potential for phenological miscuing (responding inappropriately to climate change, including a lack of response) and for phenological disjunction (in which a bird species becomes out of synchrony with its environment) are beginning to be demonstrated, and are also important areas for further research. The study of climatically induced distributional change is currently at a predictive modelling stage, and will need to develop methods for testing these predictions. Overall, there is a range of intrinsic and extrinsic factors that could potentially inhibit adaptation to climate change and these are a high priority for research.     

Seasonal population dynamics of ticks,and its influence on infection transmission: A semi-discrete approach

In this paper, a simple semi-discrete (ticks’ feeding is assumed to occur only during the summers of each year) model for tick population dynamics is presented. Conditions for existence, uniqueness, and stability of a positive equilibrium are found; the system is then studied numerically using parameter estimates calibrated for the tick Ixodes ricinus in Trentino, Italy, and the sensitivity to parameters is examined. Then, this model is extended to consider a tick-transmitted infection of one species of hosts, while other hosts are incompetent to the infection. Assuming, for simplicity, that the infection is not affecting the total number either of hosts or ticks, a threshold condition for infection persistence is obtained. The dependence of the equilibrium infection prevalence on parameters is studied numerically; in particular, we considered how infection prevalence depends on host densities. This analysis reveals that a ‘dilution effect’ occurs both for competent and for incompetent hosts; this means that, besides a lower threshold for host densities for infection to persist, there exists also an upper threshold: if host densities were higher than the upper threshold, the infection would go to extinction. Numerically, it is found that, for realistic parameter values, the upper threshold is not much higher than observed densities.     

Hill coefficient for estimating the magnitude of cooperativity in gating transitions of voltage-dependent ion channels

A frequently used measure for the extent of cooperativity in ligand binding by an allosteric protein is the Hill coefficient, obtained by fitting data of initial reaction velocity (or fractional binding saturation) as a function of substrate concentration to the Hill equation. Here, it is demonstrated that the simple two-state Boltzmann equation that is widely used to fit voltage-activation data of voltage-dependent ion channels is analogous to the Hill equation. A general empiric definition for a Hill coefficient (n(H)) for channel gating transitions that is analogous to the logarithmic potential sensitivity function of Almers is derived. This definition provides a novel framework for interpreting the meaning of the Hill coefficient. In considering three particular and simple gating schemes for a voltage-activated cation channel, the relation of the Hill coefficient to the magnitude and nature of cooperative interactions along the reaction coordinate of channel gating is demonstrated. A possible functional explanation for the low value of the Hill coefficient for gating transitions of the Shaker voltage-activated K(+) channel is suggested. The analogy between the Hill coefficients for ligand binding and for channel gating transitions further points to a unified conceptual framework in analyzing enzymes and channels behavior.     

The ethics of euthanasia: advocates' perspectives

The Netherlands is currently the only country in the world in which euthanasia is legally permissible. More specifically, Dutch law (briefly explained) allows that a doctor terminates the life of a patient of hers on his voluntary, well-considered and sustained request, if he is suffering unbearably and hopelessly. The aim of this paper is to reconstruct the Dutch debate on the moral permissibility of euthanasia so as to clarify and strengthen the various views that can be advanced in support of euthanasia. On the one view, The Pure Autonomy View (TPAV), the justification of euthanasia rests solely on the principle of respect for autonomy. That is, the reason for performing and permitting euthanasia is the patient's voluntary, well-considered and sustained, in one word: autonomous, request for euthanasia. On the alternative view, The Joint View (TJV), the principle of respect for autonomy and the principle of beneficence morally justify euthanasia together . That is, euthanasia is ethical if and partly because, since the patient is suffering unbearably and hopelessly, euthanasia is in his interest. According to this paper, there is no easy argument for one of these views rather than the other. Instead, as yet both TPAV and TJV seem inherently problematic. TPAV is unable to give a doctor a reason for performing euthanasia that appeals to her in her capacity as a doctor, such as relief of suffering. And TJV begs the question – for example, if a state were to legalize euthanasia on grounds of TJV, it would force the view upon its citizens that it may be in a person's interest to die.     

A simpler, more general method of finding the optimal foraging strategy for Bayesian birds

Oaten's (1977) stochastic model for optimal foraging in patches has been solved for a number of particular cases. A few cases, such as Poisson prey distribution and either systematic or random search, are easy to solve. In other cases, such as binomial prey distribution and random search, the form of the optimal strategy may be found using a theorem of McNamara, although more work is required to find which particular rule of the proper form is actually best. More generally (but not completely generally), optimal strategies may be found using dynamic programming. This requires that the number of prey found up to a particular time is a sufficient statistic for the number of prey remaining in a patch. This requirement cannot be dispensed with, but other simplifying assumptions that were used in the past are not necessary. In particular, it is not necessary, even for the sake of convenience, to assume that prey distribution has a form convenient for Bayesian analysis, such as a beta mixture of binomials or a gamma mixture of Poissons. Any prey distribution may be used if whatever prey are in a patch are located at random, and if search either is systematic for discrete time or for continuous time, or is random for continuous time. In earlier work, some pains had to be taken to find the rate of finding prey achieved by a given candidate strategy, but this is not necessary if expected gains and expected times are calculated routinely for each potential stopping point during dynamic programming. A new, simple method of finding optimal strategies is illustrated for discrete time and systematic search. This paper is based on a talk given at the Fifth Hans Kristiansson Symposium held in Lund, Sweden in August, 2003. The subject of the symposium was Bayesian foraging.     

Proprioception and Tension Receptors in Crab Limbs: Student Laboratory Exercises

The primary purpose of these procedures is to demonstrate for teaching and research purposes how to record the activity of living primary sensory neurons responsible for proprioception as they are detecting joint position and movement, and muscle tension. Electrical activity from crustacean proprioceptors and tension receptors is recorded by basic neurophysiological instrumentation, and a transducer is used to simultaneously measure force that is generated by stimulating a motor nerve. In addition, we demonstrate how to stain the neurons for a quick assessment of their anatomical arrangement or for permanent fixation. Staining reveals anatomical organization that is representative of chordotonal organs in most crustaceans. Comparing the tension nerve responses to the proprioceptive responses is an effective teaching tool in determining how these sensory neurons are defined functionally and how the anatomy is correlated to the function. Three staining techniques are presented allowing researchers and instructors to choose a method that is ideal for their laboratory.     

Remarks on the terminology used to describe developmental behaviour among the auks (Alcidae), with particular reference to that of the Great Auk Pinguinus impennis

Much of the historical record relating to the breeding biology of the Great Auk Pinguinus impennis consists of statements on which it is not safe to rely without corroboration. There is, nevertheless, sufficient evidence for a strong case to be argued for the species having evolved a precocial chick-rearing strategy, together with an incubation period that is remarkably brief for a bird of its size. In this way, the species would have minimized the time for which it had to remain ashore to raise its young. Before the evidence for this proposition is evaluated, a review is undertaken of the history and usage of the terminology most frequently used to describe the developmental condition of young birds on hatching. Modifications to the terminology have been suggested where there is a potential for confusion, and an entirely new term, 'hypoprecocial', introduced for downy young that require an appreciable period of brooding before quitting the breeding site. Regarding the species itself, it is suggested that the Great Auk had evolved a strategy that was more fully precocial than that of any seabird whose breeding biology is known to science.     

Use of computational fluid dynamics as a tool for establishing process design space for mixing in a bioreactor

The concept of "design space" plays an integral part in implementation of quality by design for pharmaceutical products. ICH Q8 defines design space as "the multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post-approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval." Computational fluid dynamics (CFD) is increasingly being used as a tool for modeling of hydrodynamics and mass transfer. In this study, a laboratory-scale aerated bioreactor is modeled using CFD. Eulerian-Eulerian multiphase model is used along with dispersed k-ε turbulent model. Population balance model is incorporated to account for bubble breakage and coalescence. Multiple reference frame model is used for the rotating region. We demonstrate the usefulness of CFD modeling for evaluating the effects of typical process parameters like impeller speed, gas flow rate, and liquid height on the mass transfer coefficient (k(L)a). Design of experiments is utilized to establish a design space for the above mentioned parameters for a given permissible range of k(L)a.     

Analysis of biochemical phase shift oscillators by a harmonic balancing technique

The use of harmonic balancing techniques for theoretically investigating a large class of biochemical phase shift oscillators is outlined and the accuracy of this approximate technique for large dimension nonlinear chemical systems is considered. It is concluded that for the equations under study these techniques can be successfully employed to both find periodic solutions and to indicate those cases which can not oscillate. The technique is a general one and it is possible to state a step by step procedure for its application. It has a substantial advantage in producing results which are immediately valid for arbitrary dimension. As the accuracy of the method increases with dimension, it complements classical small dimension methods. The results obtained by harmonic balancing analysis are compared with those obtained by studying the local stability properties of the singular points of the differential equation. A general theorem is derived which identifies those special cases where the results of first order harmonic balancing are identical to those of local stability analysis, and a necessary condition for this equivalence is derived. As a concrete example, the n-dimensional Goodwin oscillator is considered where p, the Hill coefficient of the feedback metabolite, is equal to three and four. It is shown that for p = 3 or 4 and n less than or equal to 4 the approximation indicates that it is impossible to construct a set of physically permissible reaction constants such that the system possesses a periodic solution. However for n greater than or equal to 5 it is always possible to find a large domain in the reaction constant space giving stable oscillations. A means of constructing such a parameter set is given. The results obtained here are compared with previously derived results for p = 1 and p = 2.     

Genome analysis technologies: towards species identification by genotype.

Traditional identification of species has been based on phenotypic traits, although it is clear that, theoretically, genotype-based classification is more accurate. This is especially the case for microorganisms which possess less identifiable traits and are more easily influenced by environment. Therefore, technology that allows identification of species based on genotype is highly desirable. Whole genome sequencing can provide a sufficient amount of information and can be determinative for this purpose but is very impractical for routine use. Thus, a competent technology is needed that allows a reproducible reduction in the amount of information required about a whole genome, while still providing sufficiently accurate identification. It is almost imperative for such a technology to be of a high cost-performance and of easy handling. Universality and portability are also strongly desired. Based on these criteria, the current state of genome analysis technologies are reviewed. Among various methodologies discussed here, amplified fragment length polymorphism (AFLP), genome profiling (GP) and microarrays are the subject of particular attention. As species identification is a base for most fields of biology including microbiology, ecology, epidemiology and for various biotechnologies, it is of paramount importance to establish a more efficient, easily handled and more objective methodology, in parallel with conventional phenotype-based methodologies. GP is currently considered to have the most optimal nature for identification of species since it can reproducibly reduce a huge amount of genome information to a manageable size by way of random polymerase chain reaction and can extract a sufficient amount of information for species identification from the DNA fragments thus profiled by temperature gradient gel electrophoresis. The potential ability of DNA microarrays for this purpose is also discussed and promises much for the future.