Lung structure and function studied by synchrotron radiation

A novel method for functional lung imaging was introduced by adapting the K-edge subtraction method (KES) to in vivo studies of small animals. In this method two synchrotron radiation energies, which bracket the K-edge of the contrast agent, are used for simultaneous recording of absorption-contrast images. Stable xenon gas is used as the contrast agent, and imaging is performed in projection or computed tomography (CT) mode. Subtraction of the two images yields the distribution of xenon, while removing practically all features due to other structures, and the xenon density can be calculated quantitatively. Because the images are recorded simultaneously, there are no movement artifacts in the subtraction image. Time resolution for a series of CT images is one image/s, which allows functional studies. Voxel size is 0.1mm3, which is an order better than in traditional lung imaging methods. KES imaging technique was used in studies of ventilation distribution and the effects of histamine-induced airway narrowing in healthy, mechanically ventilated, and anaesthetized rabbits. First, the effect of tidal volume on ventilation was studied, and the results show that an increase in tidal volume without an increase in minute ventilation results a proportional increase in regional ventilation. Second, spiral CT was used to quantify the airspace volumes in lungs in normal conditions and after histamine aerosol inhalation, and the results showed large patchy filling defects in peripheral lungs following histamine provocation. Third, the kinetics of proximal and distal airway response to histamine aerosol were examined, and the findings show that the distal airways react immediately to histamine and start to recover, while the reaction and the recovery in proximal airways is slower. Fourth, the fractal dimensions of lungs was studied, and it was found that the fractal dimension is higher at the apical part of the lungs compared to the basal part, indicating structural differences between apical and basal lung level. These results provide new insights to lung function and the effects of drug challenge studies. Nowadays the technique is available at synchrotron radiation facilities, but the compact synchrotron radiation sources are being developed, and in relatively near future the method may be used at hospitals.

Modeling of Surface UV Radiation Using Satellite Data

Solar UV radiation is harmful for life on planet Earth, but fortunately the atmospheric oxygen and ozone absorb almost entirely the most energetic UVC radiation photons. However, part of the UVB radiation and much of the UVA radiation reaches the surface of the Earth, and affect human health, environment, materials and drive atmospheric and aquatic photochemical processes. In order to quantify these effects and processes there is a need for ground-based UV measurements and radiative transfer modeling to estimate the amounts of UV radiation reaching the biosphere. Satellite measurements with their near-global spatial coverage and long-term data conti-nuity offer an attractive option for estimation of the surface UV radiation. This work focuses on radiative transfer theory based methods used for estimation of the UV radiation reaching the surface of the Earth. The objectives of the thesis were to implement the surface UV algorithm originally developed at NASA Goddard Space Flight Center for estimation of the surface UV irradiance from the meas-urements of the Dutch-Finnish built Ozone Monitoring Instrument (OMI), to improve the original surface UV algorithm especially in relation with snow cover, to validate the OMI-derived daily surface UV doses against ground-based measurements, and to demonstrate how the satellite-derived surface UV data can be used to study the effects of the UV radiation. The thesis consists of seven original papers and a summary. The summary includes an introduction of the OMI instrument, a review of the methods used for modeling of the surface UV using satellite data as well as the con-clusions of the main results of the original papers. The first two papers describe the algorithm used for estimation of the surface UV amounts from the OMI measurements as well as the unique Very Fast Delivery processing system developed for processing of the OMI data received at the Sodankylä satellite data centre. The third and the fourth papers present algorithm improvements related to the surface UV albedo of the snow-covered land. Fifth paper presents the results of the comparison of the OMI-derived daily erythemal doses with those calculated from the ground-based measurement data. It gives an estimate of the expected accuracy of the OMI-derived sur-face UV doses for various atmospheric and other conditions, and discusses the causes of the differences between the satellite-derived and ground-based data. The last two papers demonstrate the use of the satellite-derived sur-face UV data. Sixth paper presents an assessment of the photochemical decomposition rates in aquatic environment. Seventh paper presents use of satellite-derived daily surface UV doses for planning of the outdoor material weathering tests.

Radiation effects in supported nanoparticles

Nanotechnology applications are entering the market in increasing numbers, nanoparticles being among the main classes of materials used. Particles can be used, e.g., for catalysing chemical reactions, such as is done in car exhaust catalysts today. They can also modify the optical and electronic properties of materials or be used as building blocks for thin film coatings on a variety of surfaces. To develop materials for specific applications, an intricate control of the particle properties, structure, size and shape is required. All these depend on a multitude of factors from methods of synthesis and deposition to post-processing. This thesis addresses the control of nanoparticle structure by low-energy cluster beam deposition and post-synthesis ion irradiation. Cluster deposition in high vacuum offers a method for obtaining precisely controlled cluster-assembled materials with minimal contamination. Due to the clusters small size, however, the cluster-surface interaction may drastically change the cluster properties on deposition. In this thesis, the deposition process of metal and alloy clusters on metallic surfaces is modelled using molecular dynamics simulations, and the mechanisms influencing cluster structure are identified. Two mechanisms, mechanical melting upon deposition and thermally activated dislocation motion, are shown to determine whether a deposited cluster will align epitaxially with its support. The semiconductor industry has used ion irradiation as a tool to modify material properties for decades. Irradiation can be used for doping, patterning surfaces, and inducing chemical ordering in alloys, just to give a few examples. The irradiation response of nanoparticles has, however, remained an almost uncharted territory. Although irradiation effects in nanoparticles embedded inside solid matrices have been studied, almost no work has been done on supported particles. In this thesis, the response of supported nanoparticles is studied systematically for heavy and light ion irradiation. The processes leading to damage production are identified and models are developed for both types of irradiation. In recent experiments, helium irradiation has been shown to induce a phase transformation from multiply twinned to single-crystalline nanoparticles in bimetallic alloys, but the nature of the transition has remained unknown. The alloys for which the effect has been observed are CuAu and FePt. It is shown in this thesis that transient amorphization leads to the observed transition and that while CuAu and FePt do not amorphize upon irradiation in bulk or as thin films, they readily do so as nanoparticles. This is the first time such an effect is demonstrated with supported particles, not embedded in a matrix where mixing is always an issue. An understanding of the above physical processes is essential, if nanoparticles are to be used in applications in an optimal way. This thesis clarifies the mechanisms which control particle morphology, and paves way for the synthesis of nanostructured materials tailored for specific applications.

Unraveling the packing pattern leading to gelation using SS NMR and X-ray diffraction: direct observation of the evolution of self-assembled fibers

A detailed understanding of the mode of packing patterns that leads to the gelation of low molecular mass gelators derived from bile acid esters was carried out using solid state NMR along with complementary techniques such as powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and polarizing optical microscopy (POM). Solid state C-13{H-1} cross polarization (CP) magic angle spinning (MAS) NMR of the low molecularmass gel in its native state was recorded for the first time. A close resemblance in the packing patterns of the gel, xerogel and bulk solid states was revealed upon comparing their C-13{H-1} CPMAS NMR spectral pattern. A doublet resonance pattern of C-13 signals in C-13{H-1}CPMAS NMR spectra were observed for the gelator molecules, whereas the non-gelators showed simple singlet resonance or resulted inthe formation of inclusion complexes/solvates. PXRD patterns revealed a close isomorphous nature of the gelators indicating the similarity in the mode of the packing pattern in their solid state. Direct imaging of the evolution of nanofibers (sol-gel transition) was carried out using POM, which proved the presence of self-assembled fibrillar networks (SAFINs) in the gel. Finally powder X-ray structure determination revealed the presence of two non-equivalent molecules in an asymmetric unit which is responsible for the doublet resonance pattern in the solid state NMR spectra.

Oncolytic Adenoviruses with Radiation Therapy for Treatment of Prostate Cancer

Prostate cancer is the most common cancer in males. Although many patients with localized disease can be cured with surgery and radiotherapy, advanced disease and especially castration resistant metastatic disease remains incurable, with a median life expectancy of less than 18 months. Oncolytic adenoviruses (Ads) are a new promising treatment against cancer due to their innate capacity to kill cancer cells. Viral replication in tumor cells leads to oncolysis and production of a multiplicity of new virions that are capable of further destroying cancerous tissue. Oncolytic Ads can be modified for tumor targeted infection and replication and be armed with therapeutic transgenes to maximize the oncolytic effect. Worldwide, clinical trials with oncolytic Ads have demonstrated good safety while the antitumor efficacy remains to be improved. Importantly, the best responses have been reported when oncolytic adenoviruses have been combined with standard cancer treatments, such as chemotherapy and radiation. Further, a challenge in many virotherapy approaches has been the monitoring of virus replication in vivo. Reporter genes have been extensively used as transgenes to evaluate the biodistribution of the virus and activity of specific promoters. However, these techniques are often limited to preclinical evaluation and not amenable to human use. The aim of the thesis was to find and develop new oncolytic Ads with maximum efficacy against metastatic, castration resistant prostate cancer and study them in vitro and in vivo combined to different forms of radiation therapy. Using combination therapy, we were aiming for better antitumor efficacy with reduced side effects. Capsid modified Ads for enhanced transduction were studied. Serotype 3 targeted chimera, Ad5/3, was found to have enhanced infectivity for prostate cancer and was used for developing new viruses for the study. Correlation between Ad-encoded marker peptide secretion and simultaneous viral replication was evaluated and the effects of radiotherapy on viral replication were studied in detail. We found that the repair of double strand breaks caused by ionizing radiation was inhibited by adenoviral proteins and led to autophagic cell death. Both subcutaneous models and intrapulmonary tumor models mimicking metastatic, aggressive disease were used in vivo. Virus efficacy was evaluated by intratumoral injections. Also, intravenous administration was evaluated to study the effectiveness in metastatic disease. Oncolytic adenovirus treatment led to significant tumor growth control and increased the survival rate of the mice. These results were further improved when oncolytic Ads were combined with radiation therapy. Oncolytic Ads expressing human sodium/iodide transporter (hNIS) as a transgene were evaluated for their oncolytic potency and for the functionality of hNIS in vitro and in vivo. Monitoring of viral replication was also assessed using different imaging modalities relative to clinical use. SPECT imaging of tumor-bearing mice was evaluated and combined with simultaneous CT-scanning to obtain important anatomical information on biodistribution, also in a three-dimensional form. It was shown that hNIS-expressing adenoviruses could harbour a bi-functional transgene allowing for localization and imaging of viral replication. Targeted radiotherapy was applied by systemic radioiodide administration and resulted in iodide accumulation into Ad-infected tumor. The combination treatment showed significantly enhanced antitumor efficacy in mice bearing prostate cancer tumors. In summary, the results presented above aim to provide new treatment modalities for castration resistant prostate cancer. Molecular insights were provided for better understanding of the benefits of combined radiation therapy and oncolytic adenoviruses, which will hopefully facilitate the translation of the approach into clinical use for humans.

An exact similarity solution in radiation-gas-dynamics

We have found an exact similarity solution of the point explosion problem in the case when the total energy of the shock wave that is produced is not constant but decreases with time and when the loss due to radiation escape is significant. We have compared the results of our exact solution with those of exact numerical solutions of Elliot and Wang and have explained the cause why our solution differs from theirs in certain aspects.

A class of one-dimensional steady-state flows in radiation-gas-dynamics

The study of steady-state flows in radiation-gas-dynamics, when radiation pressure is negligible in comparison with gas pressure, can be reduced to the study of a single first-order ordinary differential equation in particle velocity and radiation pressure. The class of steady flows, determined by the fact that the velocities in two uniform states are real, i.e. the Rankine-Hugoniot points are real, has been discussed in detail in a previous paper by one of us, when the Mach number M of the flow in one of the uniform states (at x=+∞) is greater than one and the flow direction is in the negative direction of the x-axis. In this paper we have discussed the case when M is less than or equal to one and the flow direction is still in the negative direction of the x-axis. We have drawn the various phase planes and the integral curves in each phase plane give various steady flows. We have also discussed the appearance of discontinuities in these flows.

Strong shock with radiation near the surface of a star

The propagation of a shock wave, originating in a stellar interior, is considered when it approaches the surface of the star and assumes a self-similar character, "forgetting" its initial conditions. The flow behind the shock is assumed to be spatially isothermal rather than adiabatic to simulate the conditions of large radiative transfer near the stellar surface. The adiabatic and isothermal flows behind such a shock are compared. The exact shock-propagation laws, obtained by solving the equations in similarity variables, for different values of the parameter δ in the undisturbed density law, ρ0 ∝ xδ, and γ, the ratio of specific heats, are compared with the approximate values calculated by Whitham's characteristic rule and the two show a generally good agreement.

Possible use of self-calibration to reduce systematic uncertainties in determining distance-redshift relation via gravitational radiation from merging binaries

By observing mergers of compact objects, future gravity wave experiments would measure the luminosity distance to a large number of sources to a high precision but not their redshifts. Given the directional sensitivity of an experiment, a fraction of such sources (gold plated) can be identified optically as single objects in the direction of the source. We show that if an approximate distance-redshift relation is known then it is possible to statistically resolve those sources that have multiple galaxies in the beam. We study the feasibility of using gold plated sources to iteratively resolve the unresolved sources, obtain the self-calibrated best possible distance-redshift relation and provide an analytical expression for the accuracy achievable. We derive the lower limit on the total number of sources that is needed to achieve this accuracy through self-calibration. We show that this limit depends exponentially on the beam width and give estimates for various experimental parameters representative of future gravitational wave experiments DECIGO and BBO.

Novel composite coded pattern for small angle measurement using imaging method -art.no.62891D

A novel approach for measurement of small rotation angles using imaging method is proposed and demonstrated. A plane mirror placed on a precision rotating table is used for imaging the newly designed composite coded pattern. The imaged patterns are captured with the help of a CCD camera. The angular rotation of the plane mirror is determined from a pair of the images of the pattern, captured once before and once after affecting the tilt of the mirror. Both simulation and experimental results suggest that the proposed approach not only retains the advantages of the original imaging method but also contributes significantly to the enhancement of its measuring range (+/- 4.13 degrees with accuracy of the order of 1 arcsec).

Glowworm-inspired robot swarm for simultaneous taxis towards multiple radiation sources

This paper presents a glowworm metaphor based distributed algorithm that enables a collection of minimalist mobile robots to split into subgroups, exhibit simultaneous taxis-behavior towards, and rendezvous at multiple radiation sources such as nuclear/hazardous chemical spills and fire-origins in a fire calamity. The algorithm is based on a glowworm swarm optimization (GSO) technique that finds multiple optima of multimodal functions. The algorithm is in the same spirit as the ant-colony optimization (ACO) algorithms, but with several significant differences. The agents in the glowworm algorithm carry a luminescence quantity called luciferin along with them. Agents are thought of as glowworms that emit a light whose intensity is proportional to the associated luciferin. The key feature that is responsible for the working of the algorithm is the use of an adaptive local-decision domain, which we use effectively to detect the multiple source locations of interest. The glowworms have a finite sensor range which defines a hard limit on the local-decision domain used to compute their movements. Extensive simulations validate the feasibility of applying the glowworm algorithm to the problem of multiple source localization. We build four wheeled robots called glowworms to conduct our experiments. We use a preliminary experiment to demonstrate the basic behavioral primitives that enable each glowworm to exhibit taxis behavior towards source locations and later demonstrate a sound localization task using a set of four glowworms.

Analysis of solar radiation pressure induced coupled liberations of a gravity stabilized axisymmetric satellite

This paper presents an analysis of solar radiation pressure induced coupled librations of gravity stabilized cylindrical spacecraft with a special reference to geostationary communication satellites. The Lagrangian approach is used to obtain the corresponding equations of motion. The solar induced torques are assumed to be free of librational angles and are represented by their Fourier expansion. The response and periodic solutions are obtained through linear and nonlinear analyses, using the method of harmonic balance in the latter case. The stability conditions are obtained using Routh-Hurwitz criteria. To establish the ranges of validity the analytic response is compared with the numerical solution. Finally, values of the system parameters are suggested to make the satellite behave as desired. Among these is a possible approach to subdue the solar induced roll resonance. It is felt that the approximate analysis presented here should significantly reduce the computational efforts involved in the design and stability analysis of the systems.

Phylogenetics and biogeography of a spectacular Old World radiation of butterflies: the subtribe Mycalesina (Lepidoptera: Nymphalidae: Satyrini)

Background: Butterflies of the subtribe Mycalesina (Nymphalidae: Satyrinae) are important model organisms in ecology and evolution. This group has radiated spectacularly in the Old World tropics and presents an exciting opportunity to better understand processes of invertebrate rapid radiations. However, the generic-level taxonomy of the subtribe has been in a constant state of flux, and relationships among genera are unknown. There are six currently recognized genera in the group. Mycalesis, Lohora and Nirvanopsis are found in the Oriental region, the first of which is the most speciose genus among mycalesines, and extends into the Australasian region. Hallelesis and Bicyclus are found in mainland Africa, while Heteropsis is primarily Madagascan, with a few species in Africa. We infer the phylogeny of the group with data from three genes (total of 3139 bp) and use these data to reconstruct events in the biogeographic history of the group.,Results: The results indicate that the group Mycalesina radiated rapidly around the Oligocene-Miocene boundary. Basal relationships are unresolved, but we recover six well-supported clades. Some species of Mycalesis are nested within a primarily Madagascan clade of Heteropsis,while Nirvanopsis is nested within Lohora. The phylogeny suggests that the group had its origin either in Asia or Africa, and diversified through dispersals between the two regions, during the late Oligocene and early Miocene. The current dataset tentatively suggests that the Madagascan fauna comprises two independent radiations. The Australasian radiation shares a common ancestor derived from Asia. We discuss factors that are likely to have played a key role in the diversification of the group. Conclusions: We propose a significantly revised classification scheme for Mycalesina. We conclude that the group originated and radiated from an ancestor that was found either in Asia or Africa, with dispersals between the two regions and to Australasia. Our phylogeny paves the way for further comparative studies on this group that will help us understand the processes underlying diversification in rapid radiations of invertebrates.