Hanging drop: An in vitro air toxic exposure model using human lung cells in 2D and 3D structures

Using benzene as a candidate air toxicant and A549 cells as an in vitro cell model, we have developed and validated a hanging drop (HD) air exposure system that mimics an air liquid interface exposure to the lung for periods of 1 h to over 20 days. Dose response curves were highly reproducible for 2D cultures but more variable for 3D cultures. By comparing the HD exposure method with other classically used air exposure systems, we found that the HD exposure method is more sensitive, more reliable and cheaper to run than medium diffusion methods and the CULTEX (R) system. The concentration causing 50% of reduction of cell viability (EC50) for benzene, toluene, p-xylene, m-xylene and o-xylene to A549 cells for 1 h exposure in the HD system were similar to previous in vitro static air exposure. Not only cell viability could be assessed but also sub lethal biological endpoints such as DNA damage and interleukin expressions. An advantage of the HD exposure system is that bioavailability and cell concentrations can be derived from published physicochemical properties using a four compartment mass balance model. The modelled cellular effect concentrations EC50(cell) for 1 h exposure were very similar for benzene, toluene and three xylenes and ranged from 5 to 15 mmol/kg(dry weight) which corresponds to the intracellular concentration of narcotic chemicals in many aquatic species, confirming the high sensitivity of this exposure method. (C) 2013 Elsevier B.V. All rights reserved.

Structures of some unusual types of organic compounds

Structures of a variety of compounds isolated in reactions and elucidated with the help of spectral (uv,ir,nmr and mass) data, have been discussed. In a few cases, the assigned structures were confirmed by x-ray crystal structure analysis.

Damage assessment of structures with uncertainty by using mode-shape curvatures and fuzzy logic

Uncertainties associated with the structural model and measured vibration data may lead to unreliable damage detection. In this paper, we show that geometric and measurement uncertainty cause considerable problem in damage assessment which can be alleviated by using a fuzzy logic-based approach for damage detection. Curvature damage factor (CDF) of a tapered cantilever beam are used as damage indicators. Monte Carlo simulation (MCS) is used to study the changes in the damage indicator due to uncertainty in the geometric properties of the beam. Variation in these CDF measures due to randomness in structural parameter, further contaminated with measurement noise, are used for developing and testing a fuzzy logic system (FLS). Results show that the method correctly identifies both single and multiple damages in the structure. For example, the FLS detects damage with an average accuracy of about 95 percent in a beam having geometric uncertainty of 1 percent COV and measurement noise of 10 percent in single damage scenario. For multiple damage case, the FLS identifies damages in the beam with an average accuracy of about 94 percent in the presence of above mentioned uncertainties. The paper brings together the disparate areas of probabilistic analysis and fuzzy logic to address uncertainty in structural damage detection.

Polarized Ethylenes: Structures of (l,3-Dimethyl-2-imidazolidinylidene)malononitrile and (l,3-Dimethyl-2-perhydropyrimidinylidene)malononitrile

Crystal structures of the title compounds, (I) and (II), have been determined by three-dimensional diffraction methods. Crystals of CsHIoN 4 (I) are monoclinic, space group P21/a with Z = 4, Mr= 162, a = 7.965 (1), b = 16.232 (2), c = 7.343 (1) A, fl = 113.54 (1) °, V = 890.7 A 3, D,n = 1.218, D x = 1.208 gcm -3, g(Cu Ka, 2 = 1.5418/~) = 6.47 em -1, F(000) = 344. The crystals of C9H12N4 (II) are orthorhombic, space group P21en, with Z = 4, Mr = 176, a = 7.983 (3), b = 8.075 (2), c = 14.652 (3) ./k, V = 44.43/~3, Dm= 1.219, D x = 1.237 g cm -3, #(Mo Ka, ). = 0.7107 ,/k) = 0.868 cm -1, F(000) = 376. Both structures were solved by direct methods and refined to R = 5.8% for (I) and 5.3 % for (II). The C-C double-bond distances are 1.407 (3) in (I) and 1.429 (6)/~ in (II), appreciably longer than normal. The steric and push-pull effects result in rotation about the C=C bond, the rotation angles being 20.2 (3) in (I) and 31.5 (6) o in (II).

The structures of ethyl 1,2,2-tricyano-3,3-dimethylcyclopropane-1-carboxylate and ethyl 2',3,3'-tricyanocyclohexanespirocyclopropane-2'-carboxylate

The crystal and molecular structures of C ,,H,IN302 (I) and C14HIsN302 (II) have been determined by direct methods using three-dimensional X-ray diffractometer data. Crystals of (I) are orthorhombic, space group Pna21, with a = 14.662(6), b = 10.492(5), c = 7.375 (3)A, Z = 4, V = 1134.5 A 3, D O = 1.25 (by flotation), D e = 1.269 Mgm -a, g(MoKa) = 0.085 mm -1. Crystals of (II) are monoclinic, space group P21/a, with a = 7.886 (5), b = 22.011 (8), c = 8.100 (3) A, fl = 103.12 (5) °, Z = 4, V = 1369.2 A 3, D O = 1.23 (by flotation), D e = 1.255 Mg m -3, g(Mo Kct) = 0.080 mm -1. Least-squares full-matrix refinement based on 782 (I) and 1400 independent reflections (II) converged at R = 0.040 (I) and 0.042 (II). The effect of electron-withdrawing substituents on the geometry of the cyclopropane ring is discussed.

Discovering hidden structures in molecular data using a Bayesian partition model approach

Advancements in the analysis techniques have led to a rapid accumulation of biological data in databases. Such data often are in the form of sequences of observations, examples including DNA sequences and amino acid sequences of proteins. The scale and quality of the data give promises of answering various biologically relevant questions in more detail than what has been possible before. For example, one may wish to identify areas in an amino acid sequence, which are important for the function of the corresponding protein, or investigate how characteristics on the level of DNA sequence affect the adaptation of a bacterial species to its environment. Many of the interesting questions are intimately associated with the understanding of the evolutionary relationships among the items under consideration. The aim of this work is to develop novel statistical models and computational techniques to meet with the challenge of deriving meaning from the increasing amounts of data. Our main concern is on modeling the evolutionary relationships based on the observed molecular data. We operate within a Bayesian statistical framework, which allows a probabilistic quantification of the uncertainties related to a particular solution. As the basis of our modeling approach we utilize a partition model, which is used to describe the structure of data by appropriately dividing the data items into clusters of related items. Generalizations and modifications of the partition model are developed and applied to various problems. Large-scale data sets provide also a computational challenge. The models used to describe the data must be realistic enough to capture the essential features of the current modeling task but, at the same time, simple enough to make it possible to carry out the inference in practice. The partition model fulfills these two requirements. The problem-specific features can be taken into account by modifying the prior probability distributions of the model parameters. The computational efficiency stems from the ability to integrate out the parameters of the partition model analytically, which enables the use of efficient stochastic search algorithms.

Paleomagnetic and rock magnetic study with emphasis on the Precambrian intrusions and impact structures in Fennoscandia and South Africa

The importance of supercontinents in our understanding of the geological evolution of the planet Earth has been recently emphasized. The role of paleomagnetism in reconstructing lithospheric blocks in their ancient paleopositions is vital. Paleomagnetism is the only quantitative tool for providing ancient latitudes and azimuthal orientations of continents. It also yields information of content of the geomagnetic field in the past. In order to obtain a continuous record on the positions of continents, dated intrusive rocks are required in temporal progression. This is not always possible due to pulse-like occurrences of dykes. In this work we demonstrate that studies of meteorite impact-related rocks may fill some gaps in the paleomagnetic record. This dissertation is based on paleomagnetic and rock magnetic data obtained from samples of the Jänisjärvi impact structure (Russian Karelia, most recent 40Ar-39Ar age of 682 Ma), the Salla diabase dyke (North Finland, U-Pb 1122 Ma), the Valaam monzodioritic sill (Russian Karelia, U-Pb 1458 Ma), and the Vredefort impact structure (South Africa, 2023 Ma). The paleomagnetic study of Jänisjärvi samples was made in order to obtain a pole for Baltica, which lacks paleomagnetic data from 750 to ca. 600 Ma. The position of Baltica at ca. 700 Ma is relevant in order to verify whether the supercontinent Rodinia was already fragmented. The paleomagnetic study of the Salla dyke was conducted to examine the position of Baltica at the onset of supercontinent Rodinia's formation. The virtual geomagnetic pole (VGP) from Salla dyke provides hints that the Mesoproterozoic Baltica - Laurentia unity in the Hudsonland (Columbia, Nuna) supercontinent assembly may have lasted until 1.12 Ga. Moreover, the new VGP of Salla dyke provides new constraint on the timing of the rotation of Baltica relative to Laurentia (e.g. Gower et al., 1990). A paleomagnetic study of the Valaam sill was carried out in order to shed light into the question of existence of Baltica-Laurentia unity in the supercontinent Hudsonland. Combined with results from dyke complex of the Lake Ladoga region (Schehrbakova et al., 2008) a new robust paleomagnetic pole for Baltica is obtained. This pole places Baltica on a latitude of 10°. This low latitude location is supported also by Mesoproterozoic 1.5 1.3 Ga red-bed sedimentation (for example the Satakunta sandstone). The Vredefort impactite samples provide a well dated (2.02 Ga) pole for the Kaapvaal Craton. Rock magnetic data reveal unusually high Koenigsberger ratios (Q values) in all studied lithologies of the Vredefort dome. The high Q values are now first time also seen in samples from the Johannesburg Dome (ca. 120 km away) where there is no impact evidence. Thus, a direct causative link of high Q values to the Vredefort impact event can be ruled out.

Homogeneous model theory of metric structures

This thesis studies homogeneous classes of complete metric spaces. Over the past few decades model theory has been extended to cover a variety of nonelementary frameworks. Shelah introduced the abstact elementary classes (AEC) in the 1980s as a common framework for the study of nonelementary classes. Another direction of extension has been the development of model theory for metric structures. This thesis takes a step in the direction of combining these two by introducing an AEC-like setting for studying metric structures. To find balance between generality and the possibility to develop stability theoretic tools, we work in a homogeneous context, thus extending the usual compact approach. The homogeneous context enables the application of stability theoretic tools developed in discrete homogeneous model theory. Using these we prove categoricity transfer theorems for homogeneous metric structures with respect to isometric isomorphisms. We also show how generalized isomorphisms can be added to the class, giving a model theoretic approach to, e.g., Banach space isomorphisms or operator approximations. The novelty is the built-in treatment of these generalized isomorphisms making, e.g., stability up to perturbation the natural stability notion. With respect to these generalized isomorphisms we develop a notion of independence. It behaves well already for structures which are omega-stable up to perturbation and coincides with the one from classical homogeneous model theory over saturated enough models. We also introduce a notion of isolation and prove dominance for it.

Mathematical models on the impact of noise and dyadic molecular structures on the properties of a cardiac myocyte

In cardiac myocytes (heart muscle cells), coupling of electric signal known as the action potential to contraction of the heart depends crucially on calcium-induced calcium release (CICR) in a microdomain known as the dyad. During CICR, the peak number of free calcium ions (Ca) present in the dyad is small, typically estimated to be within range 1-100. Since the free Ca ions mediate CICR, noise in Ca signaling due to the small number of free calcium ions influences Excitation-Contraction (EC) coupling gain. Noise in Ca signaling is only one noise type influencing cardiac myocytes, e.g., ion channels playing a central role in action potential propagation are stochastic machines, each of which gates more or less randomly, which produces gating noise present in membrane currents. How various noise sources influence macroscopic properties of a myocyte, how noise is attenuated and taken advantage of are largely open questions. In this thesis, the impact of noise on CICR, EC coupling and, more generally, macroscopic properties of a cardiac myocyte is investigated at multiple levels of detail using mathematical models. Complementarily to the investigation of the impact of noise on CICR, computationally-efficient yet spatially-detailed models of CICR are developed. The results of this thesis show that (1) gating noise due to the high-activity mode of L-type calcium channels playing a major role in CICR may induce early after-depolarizations associated with polymorphic tachycardia, which is a frequent precursor to sudden cardiac death in heart failure patients; (2) an increased level of voltage noise typically increases action potential duration and it skews distribution of action potential durations toward long durations in cardiac myocytes; and that (3) while a small number of Ca ions mediate CICR, Excitation-Contraction coupling is robust against this noise source, partly due to the shape of ryanodine receptor protein structures present in the cardiac dyad.

Tannakian Formalism Applied to the Category of Mixed Hodge Structures

Many problems in analysis have been solved using the theory of Hodge structures. P. Deligne started to treat these structures in a categorical way. Following him, we introduce the categories of mixed real and complex Hodge structures. Category of mixed Hodge structures over the field of real or complex numbers is a rigid abelian tensor category, and in fact, a neutral Tannakian category. Therefore it is equivalent to the category of representations of an affine group scheme. The direct sums of pure Hodge structures of different weights over real or complex numbers can be realized as a representation of the torus group, whose complex points is the Cartesian product of two punctured complex planes. Mixed Hodge structures turn out to consist of information of a direct sum of pure Hodge structures of different weights and a nilpotent automorphism. Therefore mixed Hodge structures correspond to the representations of certain semidirect product of a nilpotent group and the torus group acting on it.

Mining Sequential Data – in Search of Segmental Structures

Segmentation is a data mining technique yielding simplified representations of sequences of ordered points. A sequence is divided into some number of homogeneous blocks, and all points within a segment are described by a single value. The focus in this thesis is on piecewise-constant segments, where the most likely description for each segment and the most likely segmentation into some number of blocks can be computed efficiently. Representing sequences as segmentations is useful in, e.g., storage and indexing tasks in sequence databases, and segmentation can be used as a tool in learning about the structure of a given sequence. The discussion in this thesis begins with basic questions related to segmentation analysis, such as choosing the number of segments, and evaluating the obtained segmentations. Standard model selection techniques are shown to perform well for the sequence segmentation task. Segmentation evaluation is proposed with respect to a known segmentation structure. Applying segmentation on certain features of a sequence is shown to yield segmentations that are significantly close to the known underlying structure. Two extensions to the basic segmentation framework are introduced: unimodal segmentation and basis segmentation. The former is concerned with segmentations where the segment descriptions first increase and then decrease, and the latter with the interplay between different dimensions and segments in the sequence. These problems are formally defined and algorithms for solving them are provided and analyzed. Practical applications for segmentation techniques include time series and data stream analysis, text analysis, and biological sequence analysis. In this thesis segmentation applications are demonstrated in analyzing genomic sequences.

Gas-crystal photoreaction: the structures of 4,4'-dimethoxy(thiobenzophenone) (I), C15H14O2S, and 4,4'-bis(dimethylamino)thiobenzophenone (II), C17H20N2S

(I): M r = 258.34, triclinic, Pi, a = 9.810 (3), b=9.635(3), e=15.015(4)A, a=79.11(2), #= 102.38 (3), y = 107.76 (3) o, V= 1308.5 A 3, Z = 4, Din= 1.318 (3) (by flotation in KI solution), D x = 1.311 g cm -3, Cu Ka, 2 = 1.5418/~, g = 20-05 cm -1, F(000) = 544, T---- 293 K, R = 0.074 for 2663 reflections. (II): M r = 284.43, monoclinic, P2~/c, a= 17.029 (5), b=6.706 (5), c= 14.629 (4), t= 113.55 (2) ° , V=1531.4A 3, Z=4, Dm=1.230(5) (by flotation in KI solution), Dx= 1.234gem -3, Mo Ka, 2 = 0.7107 A, g = 1.63 cm-1; F(000) = 608, T= 293 K, R = 0.062 for 855 reflections. The orientation of the C=S chromophores in the crystal lattice and their reactivity in the crystalline state are discussed. The C--S bonds are much shorter than the normal bond length [1.605 (4) (I), 1.665 (8) A (II) cf. 1.71 A].

Sequence effects in structures of the dinucleotides d-pApT AND d-pTpA

The H1',H2' and H2″ regions of the 270-MHz PMR spectra of two deoxydinucleotides, d-pTpA and d-pApT, have been analyzed. The coupling constants in the sugar ring indicate that both A and T sugars have a tendency to acquire 2E conformations. There is also a marginal difference in the 2E populations of the T sugar in the two dinucleotides. The trends in the chemical shifts of base protons indicate different stacking of the bases in d-pApT and d-pTpA. The sequence effects on base stacking and pentose conformation are discussed.