Random matrices: Universality of ESDs and the circular law

Given an n x n complex matrix A, let mu(A)(x, y) := 1/n vertical bar{1 <= i <= n, Re lambda(i) <= x, Im lambda(i) <= y}vertical bar be the empirical spectral distribution (ESD) of its eigenvalues lambda(i) is an element of C, i = l, ... , n. We consider the limiting distribution (both in probability and in the almost sure convergence sense) of the normalized ESD mu(1/root n An) of a random matrix A(n) = (a(ij))(1 <= i, j <= n), where the random variables a(ij) - E(a(ij)) are i.i.d. copies of a fixed random variable x with unit variance. We prove a universality principle for such ensembles, namely, that the limit distribution in question is independent of the actual choice of x. In particular, in order to compute this distribution, one can assume that x is real or complex Gaussian. As a related result, we show how laws for this ESD follow from laws for the singular value distribution of 1/root n A(n) - zI for complex z. As a corollary, we establish the circular law conjecture (both almost surely and in probability), which asserts that mu(1/root n An) converges to the uniform measure on the unit disc when the a(ij) have zero mean.

Partially conserved axial-vector current inS-matrix theory

Mandelstam�s argument that PCAC follows from assigning Lorentz quantum numberM=1 to the massless pion is examined in the context of multiparticle dual resonance model. We construct a factorisable dual model for pions which is formulated operatorially on the harmonic oscillator Fock space along the lines of Neveu-Schwarz model. The model has bothm ? andm ? as arbitrary parameters unconstrained by the duality requirement. Adler self-consistency condition is satisfied if and only if the conditionm?2?m?2=1/2 is imposed, in which case the model reduces to the chiral dual pion model of Neveu and Thorn, and Schwarz. The Lorentz quantum number of the pion in the dual model is shown to beM=0.

Passive immunization with an antibody to the beta-subunit of ovine luteinizing hormone as a method of early abortion--a feasibility study in monkeys (Macaca radiata)

Antiserum to the beta-subunit of ovine luteinizing hormone (oLH-beta) raised in monkeys (Macaca radiata) has been tested by a variety of criteria both in vivo and in vitro to establish its ability to neutralize oLH, hLH, and human chorionic gonadotropin (hCG). Passive administration of this antiserum caused inhibition of ovulation and termination of pregnancy in recipient monkeys as indicated by premature vaginal bleeding and a significant reduction in serum progesterone and estrogen levels. The results suggest that antiserum raised in monkeys against oLH-beta can neutralize monkey LH as well as monkey CG.

Functional Surfaces for Microfluidics in Proteomic Analysis

Microchips for use in biomolecular analysis show a lot of promise for medical diagnostics and biomedical basic research. Among the potential advantages are more sensitive and faster analyses as well as reduced cost and sample consumption. Due to scaling laws, the surface are to volume ratios of microfluidic chips is very high. Because of this, tailoring the surface properties and surface functionalization are very important technical issues for microchip development. This thesis studies two different types of functional surfaces, surfaces for open surface capillary microfluidics and surfaces for surface assisted laser desorption ionization mass spectrometry, and combinations thereof. Open surface capillary microfluidics can be used to transport and control liquid samples on easily accessible open surfaces simply based on surface forces, without any connections to pumps or electrical power sources. Capillary filling of open partially wetting grooves is shown to be possible with certain geometries, aspect ratios and contact angles, and a theoretical model is developed to identify complete channel filling domains, as well as partial filling domains. On the other hand, partially wetting surfaces with triangular microstructures can be used for achieving directional wetting, where the water droplets do not spread isotropically, but instead only spread to a predetermined sector. Furthermore, by patterning completely wetting and superhydrophobic areas on the same surface, complex droplet shapes are achieved, as the water stretches to make contact with the wetting surface, but does not enter into the superhydrophobic domains. Surfaces for surface assisted laser desorption ionization mass spectrometry are developed by applying various active thin film coatings on multiple substrates, in order to separate surface and bulk effects. Clear differences are observed between both surface and substrate layers. The best performance surfaces consisted of amorphous silicon coating and an inorganic-organic hybrid substrate, with nanopillars and nanopores. These surfaces are used for matrix-free ionization of drugs, peptides and proteins, and for some analytes, the detection limits were in the high attomoles. Microfluidics and laser desorption ionization surfaces are combined on a functionalized drying platforms, where the surface is used to control the shape of the deposited analyte droplet, and the shape of the initial analyte droplet affects the dried droplet solute deposition pattern. The deposited droplets can then directly detected by mass spectrometry. Utilizing this approach, results of analyte concentration, splitting and separation are demonstrated.

Identification of molecules relevant for the invasiveness of fibrosarcomas and melanomas

Cancer is becoming the leading cause of deaths in the world. As 90% of all deaths from cancer are caused by metastasis, discovery of the mechanisms behind cancer cell invasion and metastasis is of utmost importance. Only new effective therapies targeting cancer progression can reduce cancer mortality rates. The aim of this study was to identify molecules that are relevant for tumor cell invasion and spreading in fibrosarcomas and melanomas, and to analyze their potential for cancer biomarkers or therapeutic targets. First, the gene expression changes of normal cells and transformed cells showing high invasiveness, S-adenosylmethionine decarboxylase (AdoMetDC)-transfected murine fibroblasts and human melanoma cells, were studied by microarray analyses. The function of the identified candidate molecules were then studied in detail in these cell lines. Finally, the physiological relevance of the identified changes was studied by immunohistochemical analyses of human sarcoma and melanoma specimens or by a mouse xenograft model. In fibrosarcoma cells, the most remarkable change detected was a dramatic up-regulation of the actin-sequestering molecule thymosin beta 4 (TB4), which was shown to be important for the transformed phenotype of the AdoMetDC-transfected cells (Amdc-s and -as). A sponge toxin latrunculin A, inhibiting the binding of TB4 to actin, was found to selectively inhibit the migration and invasion of these cells. Further, Amdc-s-induced mouse tumors and human high-grade sarcomas were found to show intense TB4 immunostaining. In addition to TB4, integrin subunits alfa 6 and beta 7 (ItgA6 and ItgB7) were found to be up-regulated in Amdc-s and -as cells. ItgA6 was shown to dimerize mainly with ItgB1 in Amdc-s. Inhibition of ItgA6 or ItgB1 function with neutralizing antibodies fully blocked the invasiveness of Amdc-s cells, and importantly also human HT-1080 fibrosarcoma cells, in three-dimensional (3D)-Matrigel mimicking tumor extracellular matrix (ECM). By immunohistochemical analyses, strong staining for ITGA6 was detected in human high-grade fibrosarcomas and other sarcomas, especially at the invasion fronts of the tumors. In the studied melanoma cell lines, the expression levels of the adhesion-related ECM proteins tenascin-C (TN-C), fibronectin (FN), and transforming growth factor beta-induced (TGFBI) were found to be highly up-regulated. By immunohistochemistry, intense TN-C and FN staining was detected in invasive and metastatic melanoma tumors, showing co-localization (together with procollagen-I) in tubular meshworks and channels around the invading melanoma cells. In vitro, TN-C and FN were further found to directly stimulate the migration of melanoma cells in 3D-collagen-I matrix. The third candidate protein, TGFBI, was found to be an anti-adhesive molecule for melanoma cells, and knockdown of its expression in metastatic melanoma cells (TGFBI-KD cells) led to dramatically impaired tumor growth in immunocompromized mice. Interestingly, the control tumors showed intense TGFBI immunostaining in the invasion fronts, showing partial co-localization with the fibrillar FN staining, whereas the small TGFBI-KD cell-induced tumors displayed amorphous, non-fibrillar FN staining. These data suggest an important role for TGFBI in FN fibrillogenesis and melanoma progression. In conclusion, we have identified several invasion-related molecules, which show potential for cancer diagnostic or prognostic markers, or therapeutic targets. Based on our previous and present fibrosarcoma studies, we propose the possibility of using ITGA6 antagonists (affecting tumor cell adhesion) in combination with TB4 inhibitors (affecting tumor cell migration) and cathepsin L inhibitors (affecting the degradation of basement membrane and ECM proteins) for the treatment of fibrosarcomas and other tumors overexpressing these molecules. With melanoma cells, in turn, we point to the importance of three secreted ECM proteins, TN-C, FN, and TGFBI, in melanoma progression. Of these, especially the potential of TN-C as a prognostic melanoma biomarker and TGFBI as a promising therapeutic target molecule are clearly worth additional studies.

A matrix identity and perturbation expressions

An identity expressing formally the diagonal and off-diagonal elements of an inverse of a matrix is deduced employing operator techniques. Several well-known perturbation expressions for the self-energy are deduced as special cases. A new approximation and other applications following from the above formalism are briefly indicated through illustrations from a perturbed harmonic oscillator, chemisorption approximations and Kelly's result in the problem of electron correlation.

On computing an equivalent symmetric matrix for a nonsymmetric matrix

A real or a complex symmetric matrix is defined here as an equivalent symmetric matrix for a real nonsymmetric matrix if both have the same eigenvalues. An equivalent symmetric matrix is useful in computing the eigenvalues of a real nonsymmetric matrix. A procedure to compute equivalent symmetric matrices and its mathematical foundation are presented.

The effects of organic environmental toxicants on hard tissue formation in developing tooth : An in vitro study in mice

Dioxins are organic toxicants that are known to impair tooth development, especially dental hard tissue formation. The most toxic dioxin congener is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Further, clinical studies suggest that maternal smoking during pregnancy can affect child s tooth development. One of the main components of tobacco smoke is the group of non-halogenated polycyclic aromatic hydrocarbons (PAHs), a representative of which is 7,12-dimethylbenz[a]anthracene (DMBA). Tributyltin (TBT), an organic tin compound, has been shown to impair bone mineralization in experimental animals. In addition to exposure to organic toxicants, a well-established cause for enamel hypomineralization is excess fluoride intake. The principal aim of this thesis project was to examine in vitro if, in addition to dioxins, other organic environmental toxicants, like PAHs and organic tin compounds, have adverse effects on tooth development, specifically on formation and mineralization of the major dental hard tissues, the dentin and the enamel. The second aim was to investigate in vitro if fluoride could intensify the manifestation of the detrimental developmental dental effects elicited by TCDD. The study was conducted by culturing mandibular first and second molar tooth germs of E18 NMRI mouse embryos in a Trowell-type organ culture and exposing them to DMBA, TBT, and sodium fluoride (NaF) and/or TCDD at various concentrations during the secretory and mineralization stages of development. Specific methods used were HE-staining for studying cell and tissue morphology, BrdU-staining for cell proliferation, TUNEL-staining for apoptosis, and QPCR, in situ hybridization and immunohistochemistry for the expressions of selected genes associated with mineralization. This thesis work showed that DMBA, TBT, TCDD and NaF interfere with dentin and enamel formation of embryonic mouse tooth in vitro, and that fluoride can potentiate the harmful effect of TCDD. The results suggested that adverse effects of TBT involve altered expression of genes associated with mineralization, and that DMBA and TBT as well as NaF and TCDD together primarily affect dentin mineralization. Since amelogenesis does not start until mineralization of dentin begins, impaired enamel matrix secretion could be a secondary effect. Dioxins, PAHs and organotins are all liposoluble and can be transferred to the infant by breast-feeding. Since doses are usually very low, developmental toxicity on most of the organs is difficult to indentify clinically. However, tooth may act as an indicator of exposure, since the major dental hard tissues, the dentin and the enamel, are not replaced once they have been formed. Thus, disturbed dental hard tissue formation raises the question of more extensive developmental toxicity.

Monikasvoinen TAVA-partisiippi : Tutkimus suomen TAVA-partisiipin käyttökonteksteista ja verbiliittojen kieliopillistumisesta

The multifaceted passive present participle in Finnish This study investigates the uses of the passive present participle in Finnish. The participle occurs in a variety of syntactic environments and exhibits a rich polysemy. Former descriptions have treated it as a mainly modal element, but it has several non-modal uses as well. The present study provides an overview of its uses and meanings, with the main focus on the factors which trigger the modal reading. In addition, the study contains two case studies on modal periphrastic constructions consisting of the verb 'to be' and the present passive participle, the Obligation construction, e.g., on men-tä-vä [is go-pass-ptc], and the Possiblity construction, e.g., on pelaste-tta-v-i-ssa [is save-pass-ptc-pl-ine]. The study is based on empirical data of 9000 sentences obtained from i) large collections of transcribed material from Finnish dialects, ii) a corpus of modern Finnish newspaper texts, iii) corpora of Old Finnish texts. Both in colloquial and standard Finnish the reading of the participle is highly dependent of the context and determined by such factors as the overall syntactic environment and other co-occurring elements. One of the main findings here is that the Finnish passive present participle is not modal per se. The contextual modal reading arises whenever the state of affairs is conceptualized from the viewpoint of the implied subject of the participle, and the meaning of possibility or obligation depends mostly on whether the situation is pleasant or undesirable. In sections examining the grammaticalization of the Possibility and Obligation constructions, the perspective is diachronic. Both constructions have derived from copula constructions with the passive present participle as a predicate (adjective or adverb). These sections show how a linguistic change can be investigated on the basis of the patterns of usage in the empirical data. The Possibility construction is currently going through a restructuration to a passive verbal complex. The source of this construction is reflected in its present-day use by the fact that it heavily biased towards a small set of verbs. The Obligation construction has grammaticalized to a construction comparable to a compound tense. Patterns of use of the construction show that grammaticalization originates in specific syntactic constructions with an implication of practical necessity. Furthermore, it is shown that the Obligation construction has grammaticalized in different directions in standard and colloquial Finnish. Differing from the study on most typical phenomena investigated in the literature on grammaticalization of modality, the present study opens new perspectives and methods for discussion on these questions.

The neuronal cell adhesion molecule ICAM-5

The neuronal cell adhesion molecule ICAM-5 ICAM-5 (telencephalin) belongs to the intercellular adhesion molecule (ICAM)-subgroup of the immunoglobulin superfamily (IgSF). ICAMs participate in leukocyte adhesion and adhesion-dependent functions in the central nervous system (CNS) through interacting with the leukocyte-specific b2 integrins. ICAM-5 is found in the mammalian forebrain, appears at the time of birth, and is located at the cell soma and neuronal dendrites. Recent studies also show that it is important for the regulation of immune functions in the brain and for the development and maturation of neuronal synapses. The clinical importance of ICAM-5 is still under investigation; it may have a role in the development of Alzheimer s disease (AD). In this study, the role of ICAM-5 in neuronal differentiation and its associations with a-actinin and N-methyl-D-aspartic acid (NMDA) receptors were examined. NMDA receptors (NMDARs) are known to be involved in many neuronal functions, including the passage of information from one neuron to another one, and thus it was thought important to study their role related to ICAM-5. The results suggested that ICAM-5 was able to induce dendritic outgrowth through homophilic adhesion (ICAM-5 monomer binds to another ICAM-5 monomer in the same or neighbouring cell), and the homophilic binding activity appeared to be regulated by monomer/multimer transition. Moreover, ICAM-5 binding to a-actinin was shown to be important for neuritic outgrowth. It was examined whether matrix metalloproteinases (MMPs) are the main enzymes involved in ICAM-5 ectodomain cleavage. The results showed that stimulation of NMDARs leads to MMP activation, cleavage of ICAM-5 and it is accompanied by dendritic spine maturation. These findings also indicated that ICAM-5 and NMDA receptor subunit 1 (NR1) compete for binding to a-actinin, and ICAM-5 may regulate the NR1 association with the actin cytoskeleton. Thus, it is concluded that ICAM-5 is a crucial cell adhesion molecule involved in the development of neuronal synapses, especially in the regulation of dendritic spine development, and its functions may also be involved with memory formation and learning.

Simultaneous display of image and spectrum in the same plane: a generalized analysis

A generalized analysis, using the Vander Lugt operational notation, of the building block optical system comprising a single holographic optical element (HOE) for achieving simultaneous display of the spectrum and the image of an object in a single plane, has been carried out. The salient features of this analysis are: (1) it allows comprehensive characterization of the HOE, (2) it provides insights into the many possible configurations for the system, and (3) it explains the existing results in a consistent manner.

An integer arithmetic method to compute generalized matrix inverse and solve linear equations exactly

An algorithm that uses integer arithmetic is suggested. It transforms anm ×n matrix to a diagonal form (of the structure of Smith Normal Form). Then it computes a reflexive generalized inverse of the matrix exactly and hence solves a system of linear equations error-free.

Occupational chronic solvent encephalopathy in Finland 1995 - 2007 : incidence and diagnostic methods

The occurrence of occupational chronic solvent encephalopathy (CSE) seems to decrease, but still every year reveals new cases. To prevent CSE and early retirement of solvent-exposed workers, actions should focus on early CSE detection and diagnosis. Identifying the work tasks and solvent exposure associated with high risk for CSE is crucial. Clinical and exposure data of all the 128 cases diagnosed with CSE as an occupational disease in Finland during 1995-2007 was collected from the patient records at the Finnish Institute of Occupational Health (FIOH) in Helsinki. The data on the number of exposed workers in Finland were gathered from the Finnish Job-exposure Matrix (FINJEM) and the number of employed from the national workforce survey. We analyzed the work tasks and solvent exposure of CSE patients and the findings in brain magnetic resonance imaging (MRI), quantitative electroencephalography (QEEG), and event-related potentials (ERP). The annual number of new cases diminished from 18 to 3, and the incidence of CSE decreased from 8.6 to 1.2 / million employed per year. The highest incidence of CSE was in workers with their main exposure to aromatic hydrocarbons; during 1995-2006 the incidence decreased from 1.2 to 0.3 / 1 000 exposed workers per year. The work tasks with the highest incidence of CSE were floor layers and lacquerers, wooden surface finishers, and industrial, metal, or car painters. Among 71 CSE patients, brain MRI revealed atrophy or white matter hyperintensities or both in 38% of the cases. Atrophy which was associated with duration of exposure was most frequently located in the cerebellum and in the frontal or parietal brain areas. QEEG in a group of 47 patients revealed increased power of the theta band in the frontal brain area. In a group of 86 patients, the P300 amplitude of auditory ERP was decreased, but at individual level, all the amplitude values were classified as normal. In 11 CSE patients and 13 age-matched controls, ERP elicited by a multimodal paradigm including an auditory, a visual detection, and a recognition memory task under single and dual-task conditions corroborated the decrease of auditory P300 amplitude in CSE patients in single-task condition. In dual-task conditions, the auditory P300 component was, more often in patients than in controls, unrecognizable. Due to the paucity and non-specificity of the findings, brain MRI serves mainly for differential diagnostics in CSE. QEEG and auditory P300 are insensitive at individual level and not useful in the clinical diagnostics of CSE. A multimodal ERP paradigm may, however, provide a more sensitive method to diagnose slight cognitive disturbances such as CSE.

Liquid-crystal display as a spectral selector for visible spectrometers

The polarization properties of a twisted nematic liquid crystal display (TNLCD) are studied experimentally with the aim of using it as a wavelength selector. The output of a white LED is split into its constituent wavelengths with a resolution of 2-5 nm in proportion to a voltage applied to the TNLCD. The feasibility of employing the display as a wavelength selector in visible spectrometers is demonstrated. A simple inexpensive design of a spectrometer built around an LED and a TNLCD is suggested.