Peer teaching and project planning

While project work is now widespread in higher education due consideration has not been given to the development of the intellectual skills on which such work depends. As an aid to better project work peer teaching has advantages in both cost and effectiveness. However, to be effective, students must be able to call on a procedure for analysing and representing clearly the structure of the situation with which they are concerned. This can be achieved by using a simplified version of Forrester dynamic systems models. Examples are described of some typical situations in which this approach has been successfully applied.     

The moss fauna 1: Tardigrades

The Tardigrada is described as a group of animals suitable for close study in project work. Reasons for their suitability are given and an illustrated key is included.     

Turning up the heat on L-type Ca2+ channels promotes neuronal firing and seizure activity

It is well recognized clinically that fever in young children (< 6 y of age) may lead to seizure activity in a small, but significant percentage of these individuals, which may have negative consequences for the developing brain and progressive cognitive function. In rodent models, exposure of acute brain slices to hyperthermic temperatures (i.e., 38–41°C) is reported to evoke membrane depolarization and increased neuronal firing, although the underlying molecular/cellular events responsible for these phenomena are not fully understood. Elevated temperature may alter membrane excitability by influencing individual ion channels within a given neuron, or alter the behavior and connectivity of neurons and glia that operate within a local network. In the present study, Radzicki and colleagues have examined the possibility that modest increases in tissue/body temperature (up to 40.5°C) may enhance the activity of voltage-gated Ca²⁺ channels, which could then promote spontaneous firing of individual neurons and greater network discharge. The results of this work indicate that fever-like temperatures positively and reversibly influence the gating properties of L-type Ca²⁺ channels, and that the L-type blocker nimodipine reduces both temperature-induced increases in spontaneous neuronal firing and the incidence/duration of discharge activity in a whole animal model of febrile seizure.     

Bioenergetic Constraints on Primate Abundance

Explaining variation in primate population densities is central to understanding primate ecology, evolution, and conservation. Yet no researchers to date have successfully explained variation in primate population density across dietary class and phylogeny. Most previous work has focused on measures of food availability, as access to food energy likely constrains the number of individuals supported in a given area. However, energy output may provide a measure of energy constraints on population density that does not require detailed data on food availability for a given taxon. Across mammals, many studies have shown that population densities generally scale with body mass^−0.75. Because individual energy expenditures scale with body mass^0.75, population energy use (the product of population density and individual energy use) does not change with body mass, which suggests the existence of energy constraints on population density across body sizes, i.e., taxa are limited to a given amount of energy use, constraining larger taxa to lower densities. We examined population energy use and individual energy expenditure in primates and tested this energy equivalence across body mass. We also used a residual analysis to remove the effects of body mass on primate population densities and energy expenditures using basal metabolic rates (BMR; kcal/d) as a proxy for total daily energy expenditure. After taking into account phylogeny, population energy use did not significantly correlate with body mass. Larger primates, which use more energy per day, live at lower population densities than smaller primates. In addition, we found a significant negative correlation between residuals of BMR from body mass and residuals of population density from body mass after taking phylogeny into account. Thus, energy costs constrain population density across a diverse sample of primates at a given body mass, and primate species that have relatively low BMRs exist at relatively high densities. A better understanding of the determinants of primate energy costs across geography and phylogeny will ultimately help us explain and predict primate population densities.     

The fastest genome evolution ever described: HIV variation in situ

Human immunodeficiency virus is an RNA virus in which the degree of genetic variation observed is phenomenal-up to 20% within an infected individual. This is essentially due to remorseless cycles of viral replication, most probably due to chronic activation of the immune system. It can be estimated that the number of variants in existence worldwide must be in excess of 10¹⁴–10¹⁸, and given the nature of RNA viruses even more novel variants should emerge.     

Amino acid biophysical properties in the statistical prediction of peptide-MHC class I binding

Background

Peptides derived from endogenous antigens can bind to MHC class I molecules. Those which bind with high affinity can invoke a CD8⁺ immune response, resulting in the destruction of infected cells. Much work in immunoinformatics has involved the algorithmic prediction of peptide binding affinity to various MHC-I alleles. A number of tools for MHC-I binding prediction have been developed, many of which are available on the web.

Results

We hypothesize that peptides predicted by a number of tools are more likely to bind than those predicted by just one tool, and that the likelihood of a particular peptide being a binder is related to the number of tools that predict it, as well as the accuracy of those tools. To this end, we have built and tested a heuristic-based method of making MHC-binding predictions by combining the results from multiple tools. The predictive performance of each individual tool is first ascertained. These performance data are used to derive weights such that the predictions of tools with better accuracy are given greater credence. The combined tool was evaluated using ten-fold cross-validation and was found to signicantly outperform the individual tools when a high specificity threshold is used. It performs comparably well to the best-performing individual tools at lower specificity thresholds. Finally, it also outperforms the combination of the tools resulting from linear discriminant analysis.

Conclusion

A heuristic-based method of combining the results of the individual tools better facilitates the scanning of large proteomes for potential epitopes, yielding more actual high-affinity binders while reporting very few false positives.     

Impact assessment of ionizing radiation on human and non-human biota from the vicinity of a near-surface radioactive waste repository

This work describes the radiological assessment of the near-surface Maisiagala radioactive waste repository (Lithuania) over the period 2005–2012, with focus on water pathways and special emphasis on tritium. The study includes an assessment of the effect of post-closure upgrading, the durability of which is greater than 30 years. Both human and terrestrial non-human biota are considered, with local low-intensity forestry and small farms being the area of concern. The radiological exposure was evaluated using the RESRAD-OFFSITE, RESRAD-BIOTA and ERICA codes in combination with long-term data from a dedicated environmental monitoring programme. All measurements were performed at the Lithuanian Institute of Physics as part of this project. It is determined that, after repository upgrading, radiological exposure to humans are significantly lower than the human dose constraint of 0.2 mSv/year valid in the Republic of Lithuania. Likewise, for non-human biota, dose rates are below the ERICA/PROTECT screening levels. The potential annual effective inhalation dose that could be incurred by the highest-exposed human individual (which is due to tritiated water vapour airborne release over the most exposed area) does not exceed 0.1 μSv. Tritium-labelled drinking water appears to be the main pathway for human impact, representing about 83 % of the exposure. Annual committed effective dose (CED) values for members of the public consuming birch sap as medical practice are calculated to be several orders of magnitude below the CEDs for the same location associated with drinking of well water. The data presented here indicate that upper soil-layer samples may not provide a good indication of potential exposure to terrestrial deep-rooted trees, as demonstrated by an investigation of stratified ³H in soil moisture, expressed on a wet soil mass basis, in an area with subsurface contamination.     

Kinetics of ion movement in the squid giant axon

The loss of Na²², K⁴², and Cl³⁶ from single giant axons of the squid, Loligo pealii, following exposure to an artificial sea water containing these radioisotopes, occurs in two stages, an initial rapid one followed by an exponential decline. The time constants of the latter stage for the 3 ion species are, respectively, 290, 200, and 175 minutes. The outflux of sodium is depressed while that of potassium is accelerated in the absence of oxygen; the emergence of potassium is slowed by cocaine, while that of sodium is unaffected. One cm. ends of the axons take up about twice as much radiosodium as the central segment; this difference in activity is largely preserved during exposure to inactive solution. Such marked differences are not observed with radiopotassium. From the experimental data estimates are given of the influxes and outfluxes of the individual ions. The kinetics of outflux suggests a cortical layer of measureable thickness which contains the ions in different proportions from those in the medium and which governs the rate of emergence of these ions from the axon as though it contained very few but large (relative to ion dimensions) pores.     

Observations on Idiotypy of Rabbit Antibodies against <Emphasis Type="Italic">Salmonella abortus-equi</Emphasis>

IDIOTYPIC specificities are antigenic specificities each of which seems to be peculiar to antibodies of one given individual (or perhaps of one group of individuals) against one given antigen^1,2. They are detected by reactions—usually of specific precipitation-using anti-idiotypic sera³. We have used anti-Salmonella abortus-equi (SAE) sera of two rabbits to agglutinate bacteria which were injected into two series of six rabbits; three rabbits of each series gave precipitating anti-idiotypic sera.     

Transport adenosine triphosphatase activity in the rat cornea

Summary The sodium-potassium activated adenosine triphosphatase (NaKATPase) activity of the rat cornea was investigated histochemically using a Pb²⁺-precipitation technique in which adenosine triphosphate (ATP) is used as substrate and two methods for potassium-dependent para-nitrophenyl-phosphatase (K-NPPase) activity.With all the three techniques used it was demonstrated that the sodium-potassium-activated adenosine triphosphatase (NaK-ATPase) activity is localized in the cell membranes of the endothelium whereas a much weaker activity was observed in the epithelium. When the Pb²⁺-technique was used, the epithelial cell membranes showed a weaker reaction in the presence of ouabain. This activity was only Mg²⁺-dependent and was presumably due to an Mg²⁺-dependent ATPase.The validity of the histochemical techniques for NaK-ATPase activity is discussed. The results emphasize the importance of the endothelium as the main site of Na⁺ transport in the cornea. Small amounts of the enzyme are also present in the epithelium, which seems to be rich in Mg²⁺-ATPase. Provided that careful controls are performed, all the methods give consistent results in the cornea.The work is part of an eye research project by Arto Palkama and supported by grants from the Sigrid Jusélius Foundation, Helsinki, Finland, to A.P. and from the Finnish Cultural Foundation, Helsinki, Finland, to T.T. and M.P.The authors are grateful to Miss Irma Hiltunen for skilful technical assistance     

Flower visiting by hoverflies (Syrphidae)

An account is given of a study of resource-partitioning in hoverflies (Syrphidae) which feed almost exclusively on flowers. Suggestions are made for school project work using hoverflies.     

Determination of sulfonamide antibiotics by gas chromatography coupled with atomic emission detection

The paper describes the analysis of nine sulfonamides, chosen as the most widely used representatives of an important class of antibacterial drugs. Atomic emission detection has been found to allow simultaneous quantification and identification of the N¹-methylated derivatives, which are resolved efficiently by conventional capillary gas chromatography. Results are given concerning the linearity of the response and the characterization of the individual compounds by the elemental ratio of their carbon, nitrogen and sulfur content. The method looks promising for the quantitative analysis and confirmation of sulfonamide residues in complex mixtures.     

Invariant probabilities for systems in a random environment—With applications to the Brusselator

In this paper we are concerned with problems of the long-term behavior for nonlinear systems in random environment. The general model is assumed to be given by an ordinary differential equation with random parameters or random input. The disturbance process can be taken from a fairly general class of Markov processes having a bounded state space. In terms of the system’s dynamics we give sufficient conditions for the existence and uniqueness of invariant probabilities. Finally, we apply these results to the two-dimensional biochemical model which is known as the Brusselator. This work is part of a research project supported by the ‘Stiftung Volkswagenwerk’.     

BIITE: A Tool to Determine HLA Class II Epitopes from T Cell ELISpot Data

Activation of CD4⁺ T cells requires the recognition of peptides that are presented by HLA class II molecules and can be assessed experimentally using the ELISpot assay. However, even given an individual’s HLA class II genotype, identifying which class II molecule is responsible for a positive ELISpot response to a given peptide is not trivial. The two main difficulties are the number of HLA class II molecules that can potentially be formed in a single individual (3–14) and the lack of clear peptide binding motifs for class II molecules. Here, we present a Bayesian framework to interpret ELISpot data (BIITE: Bayesian Immunogenicity Inference Tool for ELISpot); specifically BIITE identifies which HLA-II:peptide combination(s) are immunogenic based on cohort ELISpot data. We apply BIITE to two ELISpot datasets and explore the expected performance using simulations. We show this method can reach high accuracies, depending on the cohort size and the success rate of the ELISpot assay within the cohort.     

Investigations on the growth and metabolism of cultured explants of Daucus carota

Summary Knowing that the element Fe essentially triggers the action of the coconut milk stimulus for the growth of carrot explants and thereafter interacts with added Mo and Mn, the effects of these trace elements on growth (fresh and dry weight) and metabolism of both nitrogenous and nitrogen-free metabolites have been determined. An outstanding effect of Fe is to determine the level of protein synthesized, and the combination of Mo with Fe increases both protein and the content of non-protein nitrogen compounds. The role of Mn seems to reside in the mobilization of the soluble (non-protein) nitrogen compounds but its effects, which tend to compete with Fe in combination with Mo, tend to divert these compounds from protein synthesis. The element Fe appears again as a key element which determines the linkage between the use of carbon from carbohydrate and its entry into nitrogen metabolism: this has been shown by the use of ¹⁴C-fructose as the source. Whereas Fe promotes the use of ¹⁴C from fructose and directs it into protein, neither Mo nor Mn could achieve this either separately or in combination. The paper presents both the individual effects due to the trace elements and their interactions when supplied in combination. Stress is laid upon the need to consider the effects which are due to the inorganic elements in combination with the componenents of such growth-promoting systems as those present in coconut milk. These interactions are illustrated by polygonal diagrams (Figs. 3, 4 and 5). The point is made that any of several single entities of such an interacting complex may be in a given case rendered limiting, and the consequences of this fact for the concept of kinins or cell division factors are outlined. Any concept that requires cell division to be mediated solely by a given kind of chemical substance, or cell-division factor, would on the evidence here given present problems.The collaboration with K. H. Neumann was made possible by a German-Cornell Exchange Scholarship tenable at Cornell University and awarded by the Deutsche Akademische Austauschdienst, Bad Godesberg. The collaboration with K. V. N. Rao was made possible by the award of a Fulbright Travel grant and a Smith-Mundt stipend. In both cases (K. H. N. and K. V. N. R.) work continued after their scholarships expired under arrangements made possible by a grant to one of us (F. C. S.) from the National Institutes of Health, Bethesda, Md. K. H. Neumann was associated with the work throughout both at Cornell University and subsequently at the Justus Liebig Universität at Giessen (Institute für Pflanzenernährung); K. V. N. Rao was concerned with the work in its later stages at Cornell.     

The Development of Artistic Perception in Schoolchildren

The elements of the material of a work of art (in literature these are the individual words or individual facts used by the author) make no aesthetic sense outside of a context. In themselves they are understandable in the particular cultural-historical environment and cause no difficulties in perception during the course of reading.¹     

Quantitative analysis of spatial-temporal correlations during germination of spores of Bacillus Species

Bacteria of Bacillus species sporulate upon starvation, and the resultant dormant spores germinate when the environment appears likely to allow the resumption of vegetative growth. Normally, the rates of germination of individual spores in populations are very heterogeneous, and the current work has investigated whether spore-to-spore communication enhances the synchronicity of germination. In order to do this work, time-lapse optical images of thousands of individual spores were captured during germination, and an image analysis algorithm was developed to do the following: (i) measure the positions and germination rates of many thousands of individual spores and (ii) compute pairwise correlations of their germination. This analysis showed that an individual spore''s germination rate was dependent on its distance from other spores, especially at short distances. Thus, spores that were within a few micrometers exhibited an increased synchronicity in germination, suggesting that there is a mechanism for short-range communication between such spores during germination. However, two molecules known to be germinants that are released during germination, l-alanine and the 1:1 chelate of Ca²⁺ and dipicolinic acid, did not mediate spore-to-spore communication during germination.     

Cortisol metabolism in the domestic cat and implications for non-invasive monitoring of adrenocortical function in endangered felids

Three domestic cats were given i.m. injections of ³H-cortisol to determine the time course and relative proportion of excreted ³H-cortisol metabolites into urine and feces. Most urinary radioactivity was detected in the first sample collected at 3.9 ± 2.5 hr postinjection and accounted for 13.9 ± 2.1% of the total radioactivity recovered. High performance liquid chromatography (HPLC) detected four urinary metabolites, one of which (13.7% urinary radioactivity) eluted with the ³H-cortisol reference tracer and was quantifiable using a commercial cortisol radioimmunoassay (RIA). The majority of cortisol metabolites in feces (85.9 ± 2.1%) was excreted at 22.3 ± 6.2 hr. HPLC analysis detected several fecal metabolites consisting primarily of nonhydolyzable water-soluble forms, none of which eluted with ³H-cortisol or ³H-corticosterone reference tracers. No immunoreactivity was detected in HPLC-separated fecal eluates using the cortisol RIA; however, two of the more polar metabolites were quantifiable using a commerical cortisosterone RIA. The physiological relevance of the immunoreactive fecal metabolites was determined in four domestic cats given an adrenocorticotropin (ACTH) challenge. Increased serum cortisol concentrations were detected within 30 min of ACTH injection, which was maintained for at least 6 hr. A corresponding increase in fecal cortisol metabolite concentrations (ranging from 238% to 826% over individual baseline values) was observed 24–48 hr later. These data indicate that adrenocortical activity can be monitored nonivasively in the cat by measuring cortisol metabolites excreted in feces. This procedure is a potentially valuable tool for endangered felid management to help evaluate responses to physiological and psychological stressors associated with environmental conditions and husbandry practices. (This article is a US Government work and, as such, is in the public domain in the United States of America.) © 1996 Wiley-Liss, Inc.