Contact-induced apical asymmetry drives the thigmotropic responses of Candida albicans hyphae

Acknowledgements We thank Marco Thiel for assistance with data interpretation, Peter Sudbery for the provision of strains and Jeremy Craven for useful discussions. This work was supported by a BBSRC-DTG to D. D. T., NIH award DK083592 to F. J. B. and P. A. J., and a Royal Society URF UF080611 and MRC NIRG 90671 to A. C. B.Non peer reviewedPublisher PD

Takagi–Sugeno Fuzzy Modeling of Skin Permeability

The skin is a major exposure route for many potentially toxic chemicals. It is, therefore, important to be able to predict the permeability of compounds through skin under a variety of conditions. Available skin permeability databases are often limited in scope and not conducive to developing effective models. This sparseness and ambiguity of available data prompted the use of fuzzy set theory to model and predict skin permeability. Using a previously published database containing 140 compounds, a rule-based Takagi–Sugeno fuzzy model is shown to predict skin permeability of compounds using octanol-water partition coefficient, molecular weight, and temperature as inputs. Model performance was estimated using a cross-validation approach. In addition, 10 data points were removed prior to model development for additional testing with new data. The fuzzy model is compared to a regression model for the same inputs using both R2 and root mean square error measures. The quality of the fuzzy model is also compared with previously published models. The statistical analysis demonstrates that the fuzzy model performs better than the regression model with identical data and validation protocols. The prediction quality for this model is similar to others that were published. The fuzzy model provides insights on the relationships between lipophilicity, molecular weight, and temperature on percutaneous penetration. This model can be used as a tool for rapid determination of initial estimates of skin permeability

Takagi–Sugeno Fuzzy Modeling of Skin Permeability

The skin is a major exposure route for many potentially toxic chemicals. It is, therefore, important to be able to predict the permeability of compounds through skin under a variety of conditions. Available skin permeability databases are often limited in scope and not conducive to developing effective models. This sparseness and ambiguity of available data prompted the use of fuzzy set theory to model and predict skin permeability. Using a previously published database containing 140 compounds, a rule-based Takagi–Sugeno fuzzy model is shown to predict skin permeability of compounds using octanol-water partition coefficient, molecular weight, and temperature as inputs. Model performance was estimated using a cross-validation approach. In addition, 10 data points were removed prior to model development for additional testing with new data. The fuzzy model is compared to a regression model for the same inputs using both R2 and root mean square error measures. The quality of the fuzzy model is also compared with previously published models. The statistical analysis demonstrates that the fuzzy model performs better than the regression model with identical data and validation protocols. The prediction quality for this model is similar to others that were published. The fuzzy model provides insights on the relationships between lipophilicity, molecular weight, and temperature on percutaneous penetration. This model can be used as a tool for rapid determination of initial estimates of skin permeability

Mapping warm molecular hydrogen with Spitzer's Infrared Array Camera (IRAC)

Photometric maps, obtained with Spitzer's Infrared Array Camera (IRAC), can provide a valuable probe of warm molecular hydrogen within the interstellar medium. IRAC maps of the supernova remnant IC443, extracted from the Spitzer archive, are strikingly similar to spectral line maps of the H2 pure rotational transitions that we obtained with the Infrared Spectrograph (IRS) instrument on Spitzer. IRS spectroscopy indicates that IRAC Bands 3 and 4 are indeed dominated by the H2 v=0-0 S(5) and S(7) transitions, respectively. Modeling of the H2 excitation suggests that Bands 1 and 2 are dominated by H2 v=1-0 O(5) and v=0-0 S(9). Large maps of the H2 emission in IC433, obtained with IRAC, show band ratios that are inconsistent with the presence of gas at a single temperature. The relative strengths of IRAC Bands 2, 3, and 4 are consistent with pure H2 emission from shocked material with a power-law distribution of gas temperatures. CO vibrational emissions do not contribute significantly to the observed Band 2 intensity. Assuming that the column density of H2 at temperatures T to T+dT is proportional to T raised to the power -b for temperatures up to 4000 K, we obtained a typical estimate of 4.5 for b. The power-law index, b, shows variations over the range 3 to 6 within the set of different sight-lines probed by the maps, with the majority of sight-lines showing b in the range 4 to 5. The observed power-law index is consistent with the predictions of simple models for paraboloidal bow shocks.Comment: 27 pages, including 11 figures. Accepted for publication in Ap

Risk of colon cancer in hereditary non-polyposis colorectal cancer patients as predicted by fuzzy modeling: Influence of smoking

AIM: To investigate whether a fuzzy logic model could predict colorectal cancer (CRC) risk engendered by smoking in hereditary non-polyposis colorectal cancer (HNPCC) patients. METHODS: Three hundred and forty HNPCC mismatch repair (MMR) mutation carriers from the Creighton University Hereditary Cancer Institute Registry were selected for modeling. Age-dependent curves were generated to elucidate the joint effects between gene mutation (hMLH1 or hMSH2), gender, and smoking status on the probability of developing CRC. RESULTS: Smoking significantly increased CRC risk in male hMSH2 mutation carriers (P \u3c 0.05). hMLH1 mutations augmented CRC risk relative to hMSH2 mutation carriers for males (P \u3c 0.05). Males had a significantly higher risk of CRC than females for hMLH1 non smokers (P \u3c 0.05), hMLH1 smokers (P \u3c 0.1) and hMSH2 smokers (P \u3c 0.1). Smoking promoted CRC in a dose-dependent manner in hMSH2 in males (P \u3c 0.05). Females with hMSH2 mutations and both sexes with the hMLH1 groups only demonstrated a smoking effect after an extensive smoking history (P \u3c 0.05). CONCLUSION: CRC promotion by smoking in HNPCC patients is dependent on gene mutation, gender and age. These data demonstrate that fuzzy modeling may enable formulation of clinical risk scores, thereby allowing individualization of CRC prevention strategies

Household Preparedness Motivation in Lahar Hazard Zones: Assessing the Adoption of Preparedness Behaviors Among Laypeople and Response Professionals in Communities Downstream from Mount Baker and Glacier Peak (USA) Volcanoes

As the number of people living at risk from volcanic hazards in the U.S. Pacific Northwest grows, more detailed studies of household preparedness in at-risk communities are needed to develop effective mitigation, response, and recovery plans. This study examines two aspects of preparedness behavior motivation in the Skagit Valley (WA), which is at risk from Mount Baker and Glacier Peak lahars. First, we examine the influence of perceived response-efficacy, protective response costs, self-efficacy, and ascription of responsibility on preparedness. Results indicate few respondents believe high perceived protective response costs, low perceived response-efficacy, or low perceived protection responsibility prevent them from adopting frequently recommended preparedness behaviors. Correlations with preparedness suggest perceived self-efficacy and ascription of responsibility play a more dominant role in determining preparedness behaviors, albeit a less readily recognized role. Second, we investigate how participation in hazard management at a professional level (e.g., working as a first responder or leader within the local city government, hospitals, school districts, Red Cross, or utilities, transportation, or water companies) influences knowledge, risk perception, and household preparedness. Results show that professional participation minimally influences household preparedness, but successfully improves perceived self-efficacy, confidence in officials, and information seeking behavior. Given these results, we argue (1) for inclusion of ascription of responsibility variables in studies of preparedness behavior motivation and (2) that specific types of participation in response-related activities (e.g., public, professional, specific training programs) may affect household preparedness differently, whereas self-efficacy and confidence in officials may improve regardless of participation type because of increased interaction with emergency officials

The Future of History: Investigating the Preservation of Information in the Digital Age

Abstract This study investigates the challenges of preserving information in the digital age, and explores how this may affect the future of historical knowledge. The study is based on a series of semi-structured interviews with forty-one historians, archivists, librarians, and web researchers. While the results reject the idea of a single ‘digital black hole’ in historical records, they emphasize the importance of the issue for the future of history, and the complexity of the solutions to be adopted. The need for planning, for education, and for cooperation between historians and the information professions is also emphasized

Bone loss and aggravated autoimmune arthritis in HLA-DRβ1-bearing humanized mice following oral challenge with Porphyromonas gingivalis

BACKGROUND: The linkage between periodontal disease and rheumatoid arthritis is well established. Commonalities among the two are that both are chronic inflammatory diseases characterized by bone loss, an association with the shared epitope susceptibility allele, and anti-citrullinated protein antibodies. METHODS: To explore immune mechanisms that may connect the two seemingly disparate disorders, we measured host immune responses including T-cell phenotype and anti-citrullinated protein antibody production in human leukocyte antigen (HLA)-DR1 humanized C57BL/6 mice following exposure to the Gram-negative anaerobic periodontal disease pathogen Porphyromonas gingivalis. We measured autoimmune arthritis disease expression in mice exposed to P. gingivalis, and also in arthritis-resistant mice by flow cytometry and multiplex cytokine-linked and enzyme-linked immunosorbent assays. We also measured femoral bone density by microcomputed tomography and systemic cytokine production. RESULTS: Exposure of the gingiva of DR1 mice to P. gingivalis results in a transient increase in the percentage of Th17 cells, both in peripheral blood and cervical lymph nodes, a burst of systemic cytokine activity, a loss in femoral bone density, and the generation of anti-citrullinated protein antibodies. Importantly, these antibodies are not produced in response to P. gingivalis treatment of wild-type C57BL/6 mice, and P. gingivalis exposure triggered expression of arthritis in arthritis-resistant mice. CONCLUSIONS: Exposure of gingival tissues to P. gingivalis has systemic effects that can result in disease pathology in tissues that are spatially removed from the initial site of infection, providing evidence for systemic effects of this periodontal pathogen. The elicitation of anti-citrullinated protein antibodies in an HLA-DR1-restricted fashion by mice exposed to P. gingivalis provides support for the role of the shared epitope in both periodontal disease and rheumatoid arthritis. The ability of P. gingivalis to induce disease expression in arthritis-resistant mice provides support for the idea that periodontal infection may be able to trigger autoimmunity if other disease-eliciting factors are already present

Parametric Forcing of Waves with Non-Monotonic Dispersion Relation: Domain Structures in Ferrofluids?

Surface waves on ferrofluids exposed to a dc-magnetic field exhibit a non-monotonic dispersion relation. The effect of a parametric driving on such waves is studied within suitable coupled Ginzburg-Landau equations. Due to the non-monotonicity the neutral curve for the excitation of standing waves can have up to three minima. The stability of the waves with respect to long-wave perturbations is determined $via$ a phase-diffusion equation. It shows that the band of stable wave numbers can split up into two or three sub-bands. The resulting competition between the wave numbers corresponding to the respective sub-bands leads quite naturally to patterns consisting of multiple domains of standing waves which differ in their wave number. The coarsening dynamics of such domain structures is addressed.Comment: 23 pages, 6 postscript figures, composed using RevTeX. Submitted to PR

The proneural wave in the Drosophila optic lobe is driven by an excitable reaction-diffusion mechanism.

In living organisms, self-organised waves of signalling activity propagate spatiotemporal information within tissues. During the development of the largest component of the visual processing centre of the Drosophila brain, a travelling wave of proneural gene expression initiates neurogenesis in the larval optic lobe primordium and drives the sequential transition of neuroepithelial cells into neuroblasts. Here, we propose that this 'proneural wave' is driven by an excitable reaction-diffusion system involving epidermal growth factor receptor (EGFR) signalling interacting with the proneural gene l'sc. Within this framework, a propagating transition zone emerges from molecular feedback and diffusion. Ectopic activation of EGFR signalling in clones within the neuroepithelium demonstrates that a transition wave can be excited anywhere in the tissue by inducing signalling activity, consistent with a key prediction of the model. Our model illuminates the physical and molecular underpinnings of proneural wave progression and suggests a generic mechanism for regulating the sequential differentiation of tissues.Wellcome Trust Royal Societ