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At least 1,099 records · Page 61

Darwinian Model Building

We present a way to generate heuristic mathematical models based on the Darwinian principles of variation and selection in a pool of individuals over many generations. Each individual has a genotype (the hereditary properties) and a phenotype (the expression of these properties in the environment). Variation is achieved by cross-over and mutation operations on the genotype which consists in the present case of a single chromosome. The genotypes 'live' in the environment of the data. Nested Sampling is used to optimize the free parameters of the models given the data, thus giving rise to the phenotypes. Selection is based on the phenotypes.The evidences which naturally follow from the Nested Sampling Algorithm are used in a second level of Nested Sampling to find increasingly better models.The data in this paper originate from the Leiden Cytology and Pathology Laboratory (LCPL), which screens pap smears for cervical cancer. We have data for 1750 women who on average underwent 5 tests each. The data on individual women are treated as a small time series. We will try to estimate the next value of the prime cancer indicator from previous tests of the same woman.

97 MATHEMATICS AND COMPUTING↗

A New F-18 Labeled PET Agent For Imaging Alzheimer's Plaques

Amyloid plaques and neurofibrillary tangles are hallmarks of Alzheimer's disease (AD). Advances in development of imaging agents have focused on targeting amyloid plaques. Notable success has been the development of C-11 labeled PIB (Pittsburgh Compound) and a number of studies have demonstrated the utility of this agent. However, the short half life of C-11 (t1/2: 20 min), is a limitation, thus has prompted the development of F-18 labeled agents. Most of these agents are derivatives of amyloid binding dyes; Congo red and Thioflavin. Some of these agents are in clinical trials with encouraging results. We have been exploring new class of agents based on 8-hydroxy quinoline, a weak metal chelator, targeting elevated levels of metals in plaques. Iodine-123 labeled clioquinol showed affinity for amyloid plaques however, it had limited brain uptake and was not successful in imaging in intact animals and humans. We have been successful in synthesizing F-18 labeled 8-hydroxy quinoline. Small animal PET/CT imaging studies with this agent showed high (7-10% ID/g), rapid brain uptake and fast washout of the agent from normal mice brains and delayed washout from transgenic Alzheimer's mice. These promising results encouraged us in further evaluation of this class of compounds for imaging AD plaques.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Monte Carlo Simulations Of The Dose Distributions From Carbon Microbeams Used In An Experimental Radiation Therapy Method

Recent upgrades of the MCNPX Monte Carlo code include transport of heavy ions. We employed the new code to simulate the energy and dose distributions produced by carbon beams in rabbit's head in and around a brain tumor. The work was within our experimental technique of interlaced carbon microbeams, which uses two 90 deg. arrays of parallel, thin planes of carbon beams (microbeams) interlacing to produce a solid beam at the target. A similar version of the method was earlier developed with synchrotron-generated x-ray microbeams. We first simulated the Bragg peak in high density polyethylene and other materials, where we could compare the calculated carbon energy deposition to the measured data produced at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The results showed that new MCNPX code gives a reasonable account of the carbon beam's dose up to {approx}200 MeV/nucleon beam energy. At higher energies, which were not relevant to our project, the model failed to reproduce the Bragg-peak's extent of increasing nuclear breakup tail. In our model calculations we determined the dose distribution along the beam path, including the angular straggling of the microbeams, and used the data for determining the optimal values of beam spacing in the array for producing adequate beam interlacing at the target. We also determined, for the purpose of Bragg-peak spreading at the target, the relative beam intensities of the consecutive exposures with stepwise lower beam energies, and simulated the resulting dose distribution in the spread out Bragg-peak. The details of the simulation methods used and the results obtained are presented.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Line scanning thermography for rapid nondestructive inspection of large scale composites

As next generation structures are utilizing larger amounts of composite materials, a rigorous and reliable method is needed to inspect these structures in order to prevent catastrophic failure and extend service life. Current inspection methods, such as ultrasonic, generally require extended down time and man hours as they are typically carried out via point-by-point measurements. A novel Line Scanning Thermography (LST) System has been developed for the non-contact, large-scale field inspection of composite structures with faster scanning times than conventional thermography systems. LST is a patented dynamic thermography technique where the heat source and thermal camera move in tandem, which allows the continuous scan of long surfaces without the loss of resolution. The current system can inspect an area of 10 in{sup 2} per 1 second, and has a resolution of 0.05x0.03 in{sup 2}. Advanced data gathering protocols have been implemented for near-real time damage visualization and post-analysis algorithms for damage interpretation. The system has been used to successfully detect defects (delamination, dry areas) in fiber-reinforced composite sandwich panels for Navy applications, as well as impact damage in composite missile cases and armor ceramic panels.

42 ENGINEERING↗

Development of Computer Tomography System for the Soft X-ray Microscope at Ritsumeikan University

A synchrotron-based full-field imaging soft x-ray microscope was tuned appropriately to perform computer tomography. The contrast and focal depth of the optical system were evaluated by using a Fresnel zone plate as a test object of variable spatial frequency. A focal depth of 15 {mu}m was obtained at the spatial frequency of 4.3 {mu}m{sup -1} according to Rayleigh's criterion. As a first trial of three-dimensional observation using this system, the cerebral cortex of the brain of a mouse, trimmed to a columnar shape by focused ion beam milling, was studied using a wavelength of 1.87-nm.

43 PARTICLE ACCELERATORS↗

High-Resolution Phase-Contrast Imaging of Submicron Particles in Unstained Lung Tissue

To access the risks and chances of deposition of submicron particles in the gas-exchange area of the lung, a precise three-dimensional (3D)-localization of the sites of deposition is essential--especially because local peaks of deposition are expected in the acinar tree and in individual alveoli. In this study we developed the workflow for such an investigation. We administered 200-nm gold particles to young adult rats by intratracheal instillation. After fixation and paraffin embedding, their lungs were imaged unstained using synchrotron radiation x-ray tomographic microscopy (SRXTM) at the beamline TOMCAT (Swiss Light Source, Villigen, Switzerland) at sample detector distances of 2.5 mm (absorption contrast) and of 52.5 mm (phase contrast). A segmentation based on a global threshold of grey levels was successfully done on absorption-contrast images for the gold and on the phase-contrast images for the tissue. The smallest spots containing gold possessed a size of 1-2 voxels of 370-nm side length. We conclude that a combination of phase and absorption contrast SRXTM imaging is necessary to obtain the correct segmentation of both tissue and gold particles. This method will be used for the 3D localization of deposited particles in the gas-exchange area of the lung.

60 APPLIED LIFE SCIENCES↗

A Comparative Study Using Numerical Methods for Surface X Ray Doses with Conventional and Digital Radiology Equipment in Pediatric Radiology

The place of the study is a pediatrics clinic which realizes a great variety of emergency, ambulatory ad hospital examinations. The radiology compartment respects work procedures and a system to ensure the quality of X ray examinations. The results show a constant for the programmator of the digital detector machine for the tension applied to the tube. For the screen-film detector machine the applied tension increases proportionally with the physical development of the child considering the trunk thickness.

61 RADIATION PROTECTION AND DOSIMETRY↗

Nanoparticles as contrast-enhancing agents in optical coherence tomography imaging of the structural components of skin: Quantitative evaluation

This work examines the effect of gold nanoshells and titania nanoparticles on the imaging contrast of structural components of skin in optical coherence tomography (OCT). Experimental data are compared to Monte Carlo (MC) simulation results. In experiments with pig skin in vivo, the epidermis - dermis contrast is improved from 0.78 {+-} 0.03 to 0.92 {+-} 0.04 by gold nanoshells applied to the skin surface and from 0.78 {+-} 0.03 to 0.86 {+-} 0.04 by titania nanoparticles. The contrast of glands is enhanced by titania from 0.68 {+-} 0.12 to 0.84 {+-} 0.07. The highest contrast is reached 120 - 150 min after applying gold nanoshells and 160 - 200 min after applying titania. According to the MC simulation results, the contrast of inclusions increases from zero to 0.85 and 0.65, respectively. (optical tomography)

77 NANOSCIENCE AND NANOTECHNOLOGY↗

Fibreoptic fluorescent microscopy in studying biological objects

The method of fluorescent microscopy is developed based on employment of a single-mode fibreoptic channel to provide high spatial resolution 3D images of large cleared biological specimens using the 488-nm excitation laser line. The transverse and axial resolution of the setup is 5 and 13 {mu}m, respectively. The transversal sample size under investigation is up to 10 mm. The in-depth scanning range depends on the sample transparency and reaches 4 mm in the experiment. The 3D images of whole mouse organs (heart, lungs, brain) and mouse embryos obtained using autofluorescence or fluorescence of exogenous markers demonstrate a high contrast and cellular-level resolution.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Interaction of silicon nanoparticles with the molecules of bovine serum albumin in aqueous solutions

Using the method of photon-correlation spectroscopy, the coefficient of translational diffusion D{sub t} and the hydrodynamic radius R of the particles in aqueous solutions of the bovine serum albumin, containing silicon nanoparticles, are determined. The character of the dependence of these parameters on the concentration of the protein indicates the absence of interaction between the studied particles in the chosen range of albumin concentrations 0.2 - 1.0 mg mL{sup -1}. (optical technologies in biophysics and medicine)

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Complex genetics cause and constrain fungal persistence in different parts of the mammalian body

Determining how genetic polymorphisms enable certain fungi to persist in mammalian hosts can improve understanding of opportunistic fungal pathogenesis, a source of substantial human morbidity and mortality. We examined the genetic basis of fungal persistence in mice using a cross between a clinical isolate and the lab reference strain of the budding yeast Saccharomyces cerevisiae. Employing chromosomally encoded DNA barcodes, we tracked the relative abundances of 822 genotyped, haploid segregants in multiple organs over time and performed linkage mapping of their persistence in hosts. Detected loci showed a mix of general and antagonistically pleiotropic effects across organs. General loci showed similar effects across all organs, while antagonistically pleiotropic loci showed contrasting effects in the brain vs the kidneys, liver, and spleen. Persistence in an organ required both generally beneficial alleles and organ-appropriate pleiotropic alleles. This genetic architecture resulted in many segregants persisting in the brain or in nonbrain organs, but few segregants persisting in all organs. These results show complex combinations of genetic polymorphisms collectively cause and constrain fungal persistence in different parts of the mammalian body.

59 BASIC BIOLOGICAL SCIENCES↗

Dynamical properties of the hydration shell of fully deuterated myoglobin

Freeze-dried perdeuterated sperm whale myoglobin was kept in a water-saturated atmosphere in order to obtain a hydration degree of 335 {sup 1}H{sub 2}O molecules per one myoglobin molecule. Incoherent neutron scattering was performed at the neutron spectrometer TOFTOF at the FRM II in an angular range of q from 0.6 to 1.8 A{sup -1} and a temperature range from 4 to 297 K. We used neutrons with a wavelength of {lambda}{alpha}E 6 A and an energy resolution of about 65 {mu}eV corresponding to motions faster than 10 ps. At temperatures above 225 K, broad lines appear in the spectra caused by quasielastic scattering. For an explanation of these lines, we assumed that there are only two types of protons, those that are part of the hydration water (72%) and those that belong to the protein (28%). The protons of the hydration water were analyzed with the diffusion model of Singwi and Sjoelander [Phys. Rev. 119, 863 (1960)]. In this model, a water molecule stays for a time {tau}{sub 0} in a bound state performing oscillatory motions. Thereafter, the molecule performs free diffusion for the time {tau}{sub 1} in a nonbound state followed again by the oscillatory motions for {tau}{sub 0} and so forth. We used the general formulation with no simplifications as {tau}{sub 0}>>{tau}{sub 1} or {tau}{sub 1}>>{tau}{sub 0}. At room temperature, we obtained {tau}{sub 0} {alpha}E 104 ps and {tau}{sub 1} {alpha}E 37 ps. For the protein bound hydrogen, the dynamics is described by a Brownian oscillator where the protons perform overdamped motions in limited space.

36 MATERIALS SCIENCE↗

Structure and Function of the Su(H)-Hairless Repressor Complex, the Major Antagonist of Notch Signaling in Drosophila melanogaster

Notch is a conserved signaling pathway that specifies cell fates in metazoans. Receptor-ligand interactions induce changes in gene expression, which is regulated by the transcription factor CBF1/Su(H)/Lag-1 (CSL). CSL interacts with coregulators to repress and activate transcription from Notch target genes. While the molecular details of the activator complex are relatively well understood, the structure-function of CSL-mediated repressor complexes is poorly defined. In Drosophila, the antagonist Hairless directly binds Su(H) (the fly CSL ortholog) to repress transcription from Notch targets. Here, we determine the X-ray structure of the Su(H)-Hairless complex bound to DNA. Hairless binding produces a large conformational change in Su(H) by interacting with residues in the hydrophobic core of Su(H), illustrating the structural plasticity of CSL molecules to interact with different binding partners. Based on the structure, we designed mutants in Hairless and Su(H) that affect binding, but do not affect formation of the activator complex. These mutants were validated in vitro by isothermal titration calorimetry and yeast two- and three-hybrid assays. Moreover, these mutants allowed us to solely characterize the repressor function of Su(H) in vivo.

59 BASIC BIOLOGICAL SCIENCES↗

Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals

Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, tick-borne viral disease. Humans are the only species known to develop illness after CCHF virus (CCHFV) infection, characterized by a nonspecific febrile illness that can progress to severe, often fatal, hemorrhagic disease. A variety of animals may serve as asymptomatic reservoirs of CCHFV in an endemic cycle of transmission. Seroepidemiological studies have been instrumental in elucidating CCHFV reservoirs and in determining endemic foci of viral transmission. Herein, we review over 50 years of CCHFV seroepidemiological studies in domestic and wild animals. Furthermore, this review highlights the role of livestock in the maintenance and transmission of CCHFV, and provides a detailed summary of seroepidemiological studies of wild animal species, reflecting their relative roles in CCHFV ecology.

59 BASIC BIOLOGICAL SCIENCES↗

Poleward Expansion of the White-Footed Mouse ( Peromyscus leucopus ) under Climate Change: Implications for the Spread of Lyme Disease

The white-footed mouse (Peromyscus leucopus) is an important reservoir host for Borrelia burgdorferi, the pathogen responsible for Lyme disease, and its distribution is expanding northward. We used an Ecological Niche Factor Analysis to identify the climatic factors associated with the distribution shift of the white-footed mouse over the last 30 years at the northern edge of its range, and modeled its current and potential future (2050) distributions using the platform BIOMOD. A mild and shorter winter is favouring the northern expansion of the white-footed mouse in Québec. With more favorable winter conditions projected by 2050, the distribution range of the white-footed mouse is expected to expand further northward by 3° latitude. We also show that today in southern Québec, the occurrence of B. burgdorferi is associated with high probability of presence of the white-footed mouse. Changes in the distribution of the white-footed mouse will likely alter the geographical range of B. burgdorferi and impact the public health in northern regions that have yet to be exposed to Lyme disease.

59 BASIC BIOLOGICAL SCIENCES↗

32 species validation of a new Illumina paired-end approach for the development of microsatellites

Development and optimization of novel species-specific microsatellites, or simple sequence repeats (SSRs) remains an important step for studies in ecology, evolution, and behavior. Numerous approaches exist for identifying new SSRs that vary widely in terms of both time and cost investments. A recent approach of using paired-end Illumina sequence data in conjunction with the bioinformatics pipeline, PAL_FINDER, has the potential to substantially reduce the cost and labor investment while also improving efficiency. However, it does not appear that the approach has been widely adopted, perhaps due to concerns over its broad applicability across taxa. Therefore, to validate the utility of the approach we developed SSRs for 32 species representing 30 families, 25 orders, 11 classes, and six phyla and optimized SSRs for 13 of the species. Overall the IPE method worked extremely well and we identified 1000s of SSRs for all species (mean = 128,485), with 17% of loci being potentially amplifiable loci, and 25% of these met our most stringent criteria designed to that avoid SSRs associated with repetitive elements. Approximately 61% of screened primers yielded strong amplification of a single locus.

54 ENVIRONMENTAL SCIENCES↗