Ultra high throughput sequencing excludes MDH1 as candidate gene for RP28-linked retinitis pigmentosa

Purpose: Mutations in IDH3B, an enzyme participating in the Krebs cycle, have recently been found to cause autosomal recessive retinitis pigmentosa (arRP). The MDH1 gene maps within the RP28 arRP linkage interval and encodes cytoplasmic malate dehydrogenase, an enzyme functionally related to IDH3B. As a proof of concept for candidate gene screening to be routinely performed by ultra high throughput sequencing (UHTs), we analyzed MDH1 in a patient from each of the two families described so far to show linkage between arRP and RP28. Methods: With genomic long-range PCR, we amplified all introns and exons of the MDH1 gene (23.4 kb). PCR products were then sequenced by short-read UHTs with no further processing. Computer-based mapping of the reads and mutation detection were performed by three independent software packages. Results: Despite the intrinsic complexity of human genome sequences, reads were easily mapped and analyzed, and all algorithms used provided the same results. The two patients were homozygous for all DNA variants identified in the region, which confirms previous linkage and homozygosity mapping results, but had different haplotypes, indicating genetic or allelic heterogeneity. None of the DNA changes detected could be associated with the disease.

Maan magneettikentän dipolimallin toimivuus inklinaatiojakauman perusteella

The magnetic field of the Earth is 99 % of the internal origin and generated in the outer liquid core by the dynamo principle. In the 19th century, Carl Friedrich Gauss proved that the field can be described by a sum of spherical harmonic terms. Presently, this theory is the basis of e.g. IGRF models (International Geomagnetic Reference Field), which are the most accurate description available for the geomagnetic field. In average, dipole forms 3/4 and non-dipolar terms 1/4 of the instantaneous field, but the temporal mean of the field is assumed to be a pure geocentric axial dipolar field. The validity of this GAD (Geocentric Axial Dipole) hypothesis has been estimated by using several methods. In this work, the testing rests on the frequency dependence of inclination with respect to latitude. Each combination of dipole (GAD), quadrupole (G2) and octupole (G3) produces a distinct inclination distribution. These theoretical distributions have been compared with those calculated from empirical observations from different continents, and last, from the entire globe. Only data from Precambrian rocks (over 542 million years old) has been used in this work. The basic assumption is that during the long-term course of drifting continents, the globe is sampled adequately. There were 2823 observations altogether in the paleomagnetic database of the University of Helsinki. The effect of the quality of observations, as well as the age and rocktype, has been tested. For comparison between theoretical and empirical distributions, chi-square testing has been applied. In addition, spatiotemporal binning has effectively been used to remove the errors caused by multiple observations. The modelling from igneous rock data tells that the average magnetic field of the Earth is best described by a combination of a geocentric dipole and a very weak octupole (less than 10 % of GAD). Filtering and binning gave distributions a more GAD-like appearance, but deviation from GAD increased as a function of the age of rocks. The distribution calculated from so called keypoles, the most reliable determinations, behaves almost like GAD, having a zero quadrupole and an octupole 1 % of GAD. In no earlier study, past-400-Ma rocks have given a result so close to GAD, but low inclinations have been prominent especially in the sedimentary data. Despite these results, a greater deal of high-quality data and a proof of the long-term randomness of the Earth's continental motions are needed to make sure the dipole model holds true.

A generalized mathematical theory and experimental verification of proportional notches

A theory and generalized synthesis procedure is advocated for the design of weir notches and orifice-notches having a base in any given shape, to a depth a, such that the discharge through it is proportional to any singular monotonically-increasing function of the depth of flow measured above a certain datum. The problem is reduced to finding an exact solution of a Volterra integral equation in Abel form. The maximization of the depth of the datum below the crest of the notch is investigated. Proof is given that for a weir notch made out of one continuous curve, and for a flow proportional to the mth power of the head, it is impossible to bring the datum lower than (2m − 1)a below the crest of the notch. A new concept of an orifice-notch, having discontinuity in the curve and a division of flow into two distinct portions, is presented. The division of flow is shown to have a beneficial effect in reducing the datum below (2m − 1)a from the crest of the weir and still maintaining the proportionality of the flow. Experimental proof with one such orifice-notch is found to have a constant coefficient of discharge of 0.625. The importance of this analysis in the design of grit chambers is emphasized.

Syntheses of the trans,meso- and racemic C11 acids, degradation products of diterpene acids

Syntheses of the isomers of the C11 acid, 1(a),3(a)- dimethylcyclohexane-1 (e),2(e),3(e)-tricarboxylic acid (A) and 1(a),3(e)-dimethylcyclohexane-1(e),2(e),3(a)-tricarboxylic acid (B), the latter by two different routes, are reported. Two of the four possible isomers of the precursor triester, trimethyl 1-methylcyclohexane-1,2,3-tricarboxylate, on individual methylation followed by hydrolysis, gave the trans,meso-acid (A), identified by comparison with an authentic sample, and the cis,trans-form (B) whose structure and configuration were proved by comparison with a specimen obtained by the unambiguous and highly stereoselective second synthesis. This demonstrated that methylation of the triester isomers occurs stereospecifically and exclusively at C-3. In the second sequence, it has been possible to assign definite conformations to four key intermediates and the final product, directly from n.m.r. spectra, from changes in these spectra accompanying specific steps, and from chemical evidence. Comparison of the n.m.r. spectra of the isomeric triesters (A) and (B) has provided unequivocal proof of the accepted trans,meso configuration for the abietic acid degradation product (A).

Rot bilong mipela

In my master's thesis I explore the political significance of logging in Papua New Guinea (PNG). In commercial logging the post-colonial state of PNG, its local communities, transnational companies and non-governmental organizations come interestingly together. The central research questions are what forms of political awareness and mobilization does commercial logging bring up in the small scale communities and how – if at all – does logging change the relationship between these communities and the state of PNG. The thesis is based on three months of ethnographic fieldwork conducted in 2007 in a village located in the East New Britain province of PNG. The village, inhabited mainly by the Mengen people, was an interesting case, because logging operations had been conducted in the area with the permission of the people, while on the other hand some villagers had formed a conservation association of their own. Parliamentary elections were also held in PNG during the time of my fieldwork. During my stay in the village I took part in the village life and conducted interviews. In addition to this, much of my material is based on informal discussions with people. On my way to and from the village I also interviewed several Papua New Guinean NGO-workers in the national and provincial capitals. In my thesis I show that environmental conservation in the village is part of a larger attempt to protect local autonomy, culture and the environment, i.e. it is a ”localistic” movement. Locals supporting conservation, as well as those supporting logging, take actively part in national parliamentary as well as local level politics. In my thesis I have attempted to unpack the notion of ”local” by examining internal power relations of the community and describing various lines of thought and opinions that base on local cultural values. Along with this, commercial logging seems also to elicit the role of the state in two-fold way in East New Britain. On the one hand, the government seeks to use logging roads built by logging companies as the basis of its own national infrastructure, even though the company roads are often of manifestably poor quality and short-lived. On the other hand, problems caused by logging, such as land disputes, create a need among local communities for the state and its services. Central themes in my thesis are the local values invested in the environment, as well as the ways in which the locals produce their environment both conceptually as well as physically. As subsistence farmers the locals depend economically on the condition of their environment. However, the value of the environment goes beyond economical questions. For example, the environment holds proof of the history of the community. Conversely, also the state and companies attempt to conceptualize, modify and administer the environment. This is done through processes such as mapping and road building, both crucial political questions in East New Britain. Here the anthropological discussion about space and place, as well as political geography are central. The diverse ways of conceptualizing the environment, as well as logging, cause often disputes about the ownership of land areas. Because of this I discuss local ways of holding the land communally, as well as PNG's land legislation and ways of dispute management. Land tenure and disputes are political questions that the locals have to deal with and in some cases these questions also create a need for the judiciary system of the state. The disputes affect also political activity, which I discuss at some length in my thesis as well. Interestingly, the locals, regardless of their political views and affiliations, establish transnational connections ranging from NGOs to government departments and multinational companies.

Essays on Stock Options, Incentives, and Managerial Action

Executive compensation and managerial behavior have received an increasing amount of attention in the financial economics literature since the mid 1970s. The purpose of this thesis is to extend our understanding of managerial compensation, especially how stock option compensation is linked to the actions undertaken by the management. Furthermore, managerial compensation is continuously and heatedly debated in the media and an emerging consensus from this discussion seems to be that there still exists gaps in our knowledge of optimal contracting. In Finland, the first executive stock options were introduced in the 1980s and throughout the last 15 years it has become increasingly popular for Finnish listed firms to use this type of managerial compensation. The empirical work in the thesis is conducted using data from Finland, in contrast to most previous studies that predominantly use U.S. data. Using Finnish data provides insight of how market conditions affect compensation and managerial action and provides an opportunity to explore what parts of the U.S. evidence can be generalized to other markets. The thesis consists of four essays. The first essay investigates the exercise policy of the executive stock option holders in Finland. In summary, Essay 1 contributes to our understanding of the exercise policies by examining both the determinants of the exercise decision and the markets reaction to the actual exercises. The second essay analyzes the factors driving stock option grants using data for Finnish publicly listed firms. Several agency theory based variables are found to have have explanatory power on the likelihood of a stock option grant. Essay 2 also contributes to our understanding of behavioral factors, such as prior stock return, as determinants of stock option compensation. The third essay investigates the tax and stock option motives for share repurchases and dividend distributions. We document strong support for the tax motive for share repurchases. Furthermore, we also analyze the dividend distribution decision in companies with stock options and find a significant difference between companies with and without dividend protected options. We thus document that the cutting of dividends found in previous U.S. studies can be avoided by dividend protection. In the fourth essay we approach the puzzle of negative skewness in stock returns from an altogether different angle than in previous studies. We suggest that negative skewness in stock returns is generated by management disclosure practices and find proof for this. More specifically, we find that negative skewness in daily returns is induced by returns for days when non-scheduled firm specific news is disclosed.

Design of incentive compatible protocols for wireless networks: A game theoretic approach

In this thesis work, we design rigorous and efficient protocols/mechanisms for different types of wireless networks using a mechanism design [1] and game theoretic approach [2]. Our work can broadly be viewed in two parts. In the first part, we concentrate on ad hoc wireless networks [3] and [4]. In particular, we consider broadcast in these networks where each node is owned by independent and selfish users. Being selfish, these nodes do not forward the broadcast packets. All existing protocols for broadcast assume that nodes forward the transit packets. So, there is need for developing new broadcast protocols to overcome node selfishness. In our paper [5], we develop a strategy proof pricing mechanism which we call immediate predecessor node pricing mechanism (IPNPM) and an efficient new broadcast protocol based on IPNPM. We show the efficacy of our proposed broadcast protocol using simulation results.

An efficient pricing based protocol for broadcasting in wireless ad hoc networks

In many applications of wireless ad hoc networks, wireless nodes are owned by rational and intelligent users. In this paper, we call nodes selfish if they are owned by independent users and their only objective is to maximize their individual goals. In such situations, it may not be possible to use the existing protocols for wireless ad hoc networks as these protocols assume that nodes follow the prescribed protocol without deviation. Stimulating cooperation among these nodes is an interesting and challenging problem. Providing incentives and pricing the transactions are well known approaches to stimulate cooperation. In this paper, we present a game theoretic framework for truthful broadcast protocol and strategy proof pricing mechanism called Immediate Predecessor Node Pricing Mechanism (IPNPM). The phrase strategy proof here means that truth revelation of cost is a weakly dominant-strategy (in game theoretic terms) for each node. In order to steer our mechanism-design approach towards practical implementation, we compute the payments to nodes using a distributed algorithm. We also propose a new protocol for broadcast in wireless ad hoc network with selfish nodes based on IPNPM. The features of the proposed broadcast protocol are reliability and a significantly reduced number of packet forwards compared to the number of network nodes, which in turn leads to less system-wide power consumption to broadcast a single packet. Our simulation results show the efficacy of the proposed broadcast protocol.

On the L2 stability of linear multidimensional time varying systems

This paper analyzes the L2 stability of solutions of systems with time-varying coefficients of the form [A + C(t)]x′ = [B + D(t)]x + u, where A, B, C, D are matrices. Following proof of a lemma, the main result is derived, according to which the system is L2 stable if the eigenvalues of the coefficient matrices are related in a simple way. A corollary of the theorem dealing with small periodic perturbations of constant coefficient systems is then proved. The paper concludes with two illustrative examples, both of which deal with the attitude dynamics of a rigid, axisymmetric, spinning satellite in an eccentric orbit, subject to gravity gradient torques.

Bounded-input/bounded-output stability of linear multidimensional time- varying systems

The present study of the stability of systems governed by a linear multidimensional time-varying equation, which are encountered in spacecraft dynamics, economics, demographics, and biological systems, gives attention the lemma dealing with L(inf) stability of an integral equation that results from the differential equation of the system under consideration. Using the proof of this lemma, the main result on L(inf) stability is derived according; a corollary of the theorem deals with constant coefficient systems perturbed by small periodic terms. (O.C.)

Rigorous scaling law for the heat current in disordered harmonic chain

We study the energy current in a model of heat conduction, first considered in detail by Casher and Lebowitz. The model consists of a one-dimensional disordered harmonic chain of n i.i.d. random masses, connected to their nearest neighbors via identical springs, and coupled at the boundaries to Langevin heat baths, with respective temperatures T_1 and T_n. Let EJ_n be the steady-state energy current across the chain, averaged over the masses. We prove that EJ_n \sim (T_1 - T_n)n^{-3/2} in the limit n \to \infty, as has been conjectured by various authors over the time. The proof relies on a new explicit representation for the elements of the product of associated transfer matrices.

Experimental Verification of the Lateral Periodicity of Axially Periodic Incoherent Fields Using the Lau Effect

General' objects, which are specially prepared to possess restricted spatial frequency spectra, have been used in the conventional Lau experiment to obtain experimental proof for the existence of lateral periodicity arising from axial periodicity, for a subclass of axially periodic wavefields in an incoherent situation.

Models of Dispersal and Diversification

Ecology and evolutionary biology is the study of life on this planet. One of the many methods applied to answering the great diversity of questions regarding the lives and characteristics of individual organisms, is the utilization of mathematical models. Such models are used in a wide variety of ways. Some help us to reason, functioning as aids to, or substitutes for, our own fallible logic, thus making argumentation and thinking clearer. Models which help our reasoning can lead to conceptual clarification; by expressing ideas in algebraic terms, the relationship between different concepts become clearer. Other mathematical models are used to better understand yet more complicated models, or to develop mathematical tools for their analysis. Though helping us to reason and being used as tools in the craftmanship of science, many models do not tell us much about the real biological phenomena we are, at least initially, interested in. The main reason for this is that any mathematical model is a simplification of the real world, reducing the complexity and variety of interactions and idiosynchracies of individual organisms. What such models can tell us, however, both is and has been very valuable throughout the history of ecology and evolution. Minimally, a model simplifying the complex world can tell us that in principle, the patterns produced in a model could also be produced in the real world. We can never know how different a simplified mathematical representation is from the real world, but the similarity models do strive for, gives us confidence that their results could apply. This thesis deals with a variety of different models, used for different purposes. One model deals with how one can measure and analyse invasions; the expanding phase of invasive species. Earlier analyses claims to have shown that such invasions can be a regulated phenomena, that higher invasion speeds at a given point in time will lead to a reduction in speed. Two simple mathematical models show that analysis on this particular measure of invasion speed need not be evidence of regulation. In the context of dispersal evolution, two models acting as proof-of-principle are presented. Parent-offspring conflict emerges when there are different evolutionary optima for adaptive behavior for parents and offspring. We show that the evolution of dispersal distances can entail such a conflict, and that under parental control of dispersal (as, for example, in higher plants) wider dispersal kernels are optimal. We also show that dispersal homeostasis can be optimal; in a setting where dispersal decisions (to leave or stay in a natal patch) are made, strategies that divide their seeds or eggs into fractions that disperse or not, as opposed to randomized for each seed, can prevail. We also present a model of the evolution of bet-hedging strategies; evolutionary adaptations that occur despite their fitness, on average, being lower than a competing strategy. Such strategies can win in the long run because they have a reduced variance in fitness coupled with a reduction in mean fitness, and fitness is of a multiplicative nature across generations, and therefore sensitive to variability. This model is used for conceptual clarification; by developing a population genetical model with uncertain fitness and expressing genotypic variance in fitness as a product between individual level variance and correlations between individuals of a genotype. We arrive at expressions that intuitively reflect two of the main categorizations of bet-hedging strategies; conservative vs diversifying and within- vs between-generation bet hedging. In addition, this model shows that these divisions in fact are false dichotomies.

On the alleged equivalence of certain field theories

Abstract. We critically examine some recent claims that certain field theories with and without boson kinetic energy terms are equivalent. We point out that the crucial element in these claims is the finiteness or otherwise of the boson wavefunction renormalisation constant. We show that when this constant is finite, the equivalence proof offered in the literature fails in a direct way. When the constant is divergent, the claimed equivalence is only a consequence of improper use of divergent quantities.

Heme is a positive regulator of cytochrome P-450 gene transcription

Inhibitors of heme biosynthesis such as CoCl2, 3-amino-1,2,4-triazole, and thioacetamide block the 3-methylcholanthrene-mediated induction of cytochrome P-450 (c + d) messenger RNAs and their transcription in rat liver. This effect is specific, since the messenger RNA levels for albumin and glutathione transferase (Ya + Yc) and their transcription are not significantly influenced under conditions of heme depletion. Exogenous administration of heme at very low doses (50 μg/100 g body wt) is able to completely counteract the effects of the heme biosynthetic inhibitors on cytochrome P-450 (c + d) messenger RNA levels and their transcription. This constitutes a direct proof for the role of heme as a positive regulator of cytochrome P-450 gene transcription.