Mining of biological data I: identifying discriminating features via mean hypothesis testing

Large volumes of data are routinely collected during bioprocess operations and, more recently, in basic biological research using genomics-based technologies. While these data often lack sufficient detail to be used for mechanism identification, it is possible that the underlying mechanisms affecting cell phenotype or process outcome are reflected as specific patterns in the overall or temporal sensor logs. This raises the possibility of identifying outcome-specific fingerprints that can be used for process or phenotype classification and the identification of discriminating characteristics, such as specific genes or process variables. The aim of this work is to provide a systematic approach to identifying and modeling patterns in historical records and using this information for process classification. This approach differs from others in that emphasis is placed on analyzing the data structure first and thereby extracting potentially relevant features prior to model creation. The initial step in this overall approach is to first identify the discriminating features of the relevant measurements and time windows, which can then be subsequently used to discriminate among different classes of process behavior. This is achieved via a mean hypothesis testing algorithm. Next, the homogeneity of the multivariate data in each class is explored via a novel cluster analysis technique called PC1 Time Series Clustering to ensure that the data subsets used accurately reflect the variability displayed in the historical records. This will be the topic of the second paper in this series. We present here the method for identifying discriminating features in data via mean hypothesis testing along with results from the analysis of case studies from industrial fermentations Copyright 2000 Academic Press.     

Metallophytes—a view from the rhizosphere

Abundance of Fabaceae declines in representation through post-fire-succession in fynbos vegetation of the Cape Floristic Region (CFR). This reduction in legume occurrence coincides with a known decline in post-fire soil P availability. It was hypothesized that the disappearance of legume species during post-fire succession is due to an inability to acquire P effectively from sparingly soluble sources. P-acquisition strategies and response to P supply were compared between legume (Aspalathus, Cyclopia, Indigofera, Podalyria) and non-legume (Elegia, Leucadendron, Protea) genera when supplied with 1 or 10 mg P kg^?1 dry sand. Each genus consisted of a seeder (non-persistent) and resprouter (persistent) species. Non-legumes showed a greater investment in below-ground biomass, more root clusters, with higher concentrations of carboxylates exuded by cluster roots and carboxylates that were better suited to the mobilization of sparingly soluble P compared to legumes. The growth response to increased P supply was 53% higher in legumes than in non-legumes. The lack of a growth response to an elevated P supply in the non-legumes was attributed to N-limitation. Legume resprouters had a higher investment in cluster-root biomass and a lower capacity to down-regulate P-uptake than the seeders. Therefore the inability to acquire sufficient P from low concentration and sparingly soluble soil P-sources may contribute to the lack of indigenous legume persistence in fynbos vegetation of the CFR.     

beta-Alkylthio indolyl carbinols: potent nonsteroidal antiandrogens with oral efficacy in a prostate cancer model

Through an in vivo screening model, we developed the in vivo SAR of beta-alkylthio indolyl carbinols. Through these efforts we identified a compound with potent oral in vivo efficacy in both immature and mature rat prostate weight reduction models and in a murine xenograft prostate cancer model.     

Disgust sensitivity and the neurophysiology of left-right political orientations

Disgust has been described as the most primitive and central of emotions. Thus, it is not surprising that it shapes behaviors in a variety of organisms and in a variety of contexts--including homo sapien politics. People who believe they would be bothered by a range of hypothetical disgusting situations display an increased likelihood of displaying right-of-center rather than left-of-center political orientations. Given its primal nature and essential value in avoiding pathogens disgust likely has an effect even without registering in conscious beliefs. In this article, we demonstrate that individuals with marked involuntary physiological responses to disgusting images, such as of a man eating a large mouthful of writhing worms, are more likely to self-identify as conservative and, especially, to oppose gay marriage than are individuals with more muted physiological responses to the same images. This relationship holds even when controlling for the degree to which respondents believe themselves to be disgust sensitive and suggests that people's physiological predispositions help to shape their political orientations.     

Effects of alpha-synuclein immunization in a mouse model of Parkinson's disease

Abnormal folding of alpha-synuclein (alpha-syn) is thought to lead to neurodegeneration and the characteristic symptoms of Lewy body disease (LBD). Since previous studies suggest that immunization might be a potential therapy for Alzheimer's disease, we hypothesized that immunization with human (h)alpha-syn might have therapeutic effects in LBD. For this purpose, halpha-syn transgenic (tg) mice were vaccinated with halpha-syn. In mice that produced high relative affinity antibodies, there was decreased accumulation of aggregated halpha-syn in neuronal cell bodies and synapses that was associated with reduced neurodegeneration. Furthermore, antibodies produced by immunized mice recognized abnormal halpha-syn associated with the neuronal membrane and promoted the degradation of halpha-syn aggregates, probably via lysosomal pathways. Similar effects were observed with an exogenously applied FITC-tagged halpha-syn antibody. These results suggest that vaccination is effective in reducing neuronal accumulation of halpha-syn aggregates and that further development of this approach might have a potential role in the treatment of LBD.     

Population trends associated with skin peptide defenses against chytridiomycosis in Australian frogs

Many species of amphibians in the wet tropics of Australia have experienced population declines linked with the emergence of a skin-invasive chytrid fungus, Batrachochytrium dendrobatidis. An innate defense, antimicrobial peptides produced by granular glands in the skin, may protect some species from disease. Here we present evidence that supports this hypothesis. We tested ten synthesized peptides produced by Australian species, and natural peptide mixtures from five Queensland rainforest species. Natural mixtures and most peptides tested in isolation inhibited growth of B. dendrobatidis in vitro. The three most active peptides (caerin 1.9, maculatin 1.1, and caerin 1.1) were found in the secretions of non-declining species (Litoria chloris, L. caerulea, and L. genimaculata). Although the possession of a potent isolated antimicrobial peptide does not guarantee protection from infection, non-declining species (L. lesueuri and L. genimaculata) inhabiting the rainforest of Queensland possess mixtures of peptides that may be more protective than those of the species occurring in the same habitat that have recently experienced population declines associated with chytridiomycosis (L. nannotis, L. rheocola, and Nyctimystes dayi). This study demonstrates that in vitro effectiveness of skin peptides correlates with the degree of decline in the face of an emerging pathogen. Further research is needed to assess whether this non-specific immune defense may be useful in predicting disease susceptibility in other species.     

Does waterproofing Thermochron iButton dataloggers influence temperature readings?

Miniature Thermochron iButton dataloggers have transformed the ways in which researchers collect thermal data. However, one important limitation is that these dataloggers are not waterproof, which can lead to device failure and loss of data under field conditions. Several methods have been used to increase their water resistance, but no study to date has investigated whether any of these techniques affects the accuracy of temperature readings. Waterproofing potentially could affect the accuracy of iButtons by biasing temperatures or altering rates of warming and cooling. We compared temperature profiles of unmodified Thermochron iButtons (model DS1921G) to iButtons that we coated with a clear plastic dip (designed to coat tool handles) to determine whether this waterproof coating affects the accuracy of temperatures they record. We also compared temperatures recorded by uncoated and coated iButtons that were embedded within physical models that mimic frog body temperatures. Finally, we used our field data to test whether coating iButtons with plastic prevents failure of dataloggers during fieldwork. Although we found statistically significant differences between the temperatures recorded by uncoated and coated iButtons, and also between uncoated and coated iButtons embedded in frog models, these effects were relatively small (0–1.3 °C). We also found that coating iButtons with plastic reduced the likelihood of device failure under field conditions (from 8.3% to 0%). We conclude that coating Thermochron iButtons with plastic is an affordable and reliable method of waterproofing dataloggers that prevents device failure and data loss with minimal influence on temperature readings.