Molecular genetics of X-linked cone-rod dystrophy and Åland Island eye disease

Inherited retinal diseases are the most common cause of vision loss among the working population in Western countries. It is estimated that ~1 of the people worldwide suffer from vision loss due to inherited retinal diseases. The severity of these diseases varies from partial vision loss to total blindness, and at the moment no effective cure exists. To date, nearly 200 mapped loci, including 140 cloned genes for inherited retinal diseases have been identified. By a rough estimation 50% of the retinal dystrophy genes still await discovery. In this thesis we aimed to study the genetic background of two inherited retinal diseases, X-linked cone-rod dystrophy and Åland Island eye disease. X-linked cone-rod dystrophy (CORDX) is characterized by progressive loss of visual function in school age or early adulthood. Affected males show reduced visual acuity, photophobia, myopia, color vision defects, central scotomas, and variable changes in fundus. The disease is genetically heterogeneous and two disease loci, CORDX1 and CORDX2, were known prior to the present thesis work. CORDX1, located on Xp21.1-11.4, is caused by mutations in the RPGR gene. CORDX2 is located on Xq27-28 but the causative gene is still unknown. Åland Island eye disease (AIED), originally described in a family living in Åland Islands, is a congenital retinal disease characterized by decreased visual acuity, fundus hypopigmentation, nystagmus, astigmatism, red color vision defect, myopia, and defective night vision. AIED shares similarities with another retinal disease, congenital stationary night blindness (CSNB2). Mutations in the L-type calcium channel α1F-subunit gene, CACNA1F, are known to cause CSNB2, as well as AIED-like disease. The disease locus of the original AIED family maps to the same genetic interval as the CACNA1F gene, but efforts to reveal CACNA1F mutations in patients of the original AIED family have been unsuccessful. The specific aims of this study were to map the disease gene in a large Finnish family with X-linked cone-rod dystrophy and to identify the disease-causing genes in the patients of the Finnish cone-rod dystrophy family and the original AIED family. With the help of linkage and haplotype analyses, we could localize the disease gene of the Finnish cone-rod dystrophy family to the Xp11.4-Xq13.1 region, and thus establish a new genetic X-linked cone-rod dystrophy locus, CORDX3. Mutation analyses of candidate genes revealed three novel CACNA1F gene mutations: IVS28-1 GCGTC>TGG in CORDX3 patients, a 425 bp deletion, comprising exon 30 and flanking intronic regions in AIED patients, and IVS16+2T>C in an additional Finnish patient with a CSNB2-like phenotype. All three novel mutations altered splice sites of the CACNA1F gene, and resulted in defective pre-mRNA splicing suggesting altered or absent channel function as a disease mechanism. The analyses of CACNA1F mRNA also revealed novel alternative wt splice variants, which may enhance channel diversity or regulate the overall expression level of the channel. The results of our studies may be utilized in genetic counseling of the families, and they provide a basis for studies on the pathogenesis of these diseases. In the future, the knowledge of the genetic defects may be used in the identification of specific therapies for the patients.

Pre-maps : An Educational Programme for Reading Tactile Maps

It is demanding for children with visual impairment to become aware of the world beyond their immediate experience. They need to learn to control spatial experiences as a whole and understand the relationships between objects, surfaces and themselves. Tactile maps can be an excellent source of information for depicting space and environment. By means of tactile maps children can develop their spatial understanding more efficiently than through direct travel experiences supplemented with verbal explanations. Tactile maps can help children when they are learning to understand environmental, spatial, and directional concepts. The ability to read tactile maps is not self-evident; it is a skill, which must be learned. The main research question was: can children who are visually impaired learn to read tactile maps at the preschool age if they receive structural teaching? The purpose of this study was to develop an educational program for preschool children with visual impairment, the aim of which was to teach them to read tactile maps in order to strengthen their orientation skills and to encourage them to explore the world beyond their immediate experience. The study is a multiple case study describing the development of the map program consisting of eight learning tasks. The program was developed with one preschooler who was blind, and subsequently the program was implemented with three other children. Two of the children were blind from birth, one child had lost her vision at the age of two, and one child had low vision. The program was implemented in a normal preschool. Another objective of the pre-map program was to teach the preschooler with visual impairment to understand the concept of a map. The teaching tools were simple, map-like representations called pre-maps. Before a child with visual impairment can read a comprehensive tactile map, it is important to learn to understand map symbols, and how a three-dimensional model changes to a two-dimensional tactile map. All teaching sessions were videotaped; the results are based on the analysis of the videotapes. Two of the children completed the program successfully, and learned to read a tactile map. The two other children felt happy during the sessions, but it was problematic for them to engage fully in the instruction. One of the two eventually completed the program, while the other developed predominantly emerging skills. The results of the children's performances and the positive feedback from the teachers, assistants and the parents proved that this pre-map program is appropriate teaching material for preschool children who are visually impaired. The program does not demand high-level expertise; also parents, preschool teachers, and school assistants can carry out the program.

Composition operators, Aleksandrov measures and value distribution of analytic maps in the unit disc

A composition operator is a linear operator that precomposes any given function with another function, which is held fixed and called the symbol of the composition operator. This dissertation studies such operators and questions related to their theory in the case when the functions to be composed are analytic in the unit disc of the complex plane. Thus the subject of the dissertation lies at the intersection of analytic function theory and operator theory. The work contains three research articles. The first article is concerned with the value distribution of analytic functions. In the literature there are two different conditions which characterize when a composition operator is compact on the Hardy spaces of the unit disc. One condition is in terms of the classical Nevanlinna counting function, defined inside the disc, and the other condition involves a family of certain measures called the Aleksandrov (or Clark) measures and supported on the boundary of the disc. The article explains the connection between these two approaches from a function-theoretic point of view. It is shown that the Aleksandrov measures can be interpreted as kinds of boundary limits of the Nevanlinna counting function as one approaches the boundary from within the disc. The other two articles investigate the compactness properties of the difference of two composition operators, which is beneficial for understanding the structure of the set of all composition operators. The second article considers this question on the Hardy and related spaces of the disc, and employs Aleksandrov measures as its main tool. The results obtained generalize those existing for the case of a single composition operator. However, there are some peculiarities which do not occur in the theory of a single operator. The third article studies the compactness of the difference operator on the Bloch and Lipschitz spaces, improving and extending results given in the previous literature. Moreover, in this connection one obtains a general result which characterizes the compactness and weak compactness of the difference of two weighted composition operators on certain weighted Hardy-type spaces.

The influence of school smoking policy and school prevention programs on the smoking behaviour of high school students in Prince Edward Island, Canada

The aim of the study was to examine the influence of school smoking policy and school smoking prevention programs on the smoking behaviour of students in high schools in Prince Edward Island using the School Health Action Planning Evaluation System (SHAPES). A total sample included 13,131 observations of students in grades 10-12 in ten high schools in Prince Edward Island over three waves of data collection (1999, 2000, and 2001). Changes in prevalence of smoking and factors influencing smoking behaviour were analyzed using descriptive statistics and Chi-Square tests. Multi-level logistic regression analyses were used to examine how both school and student characteristics were associated with smoking behaviour (I, II, III, IV). Since students were located within schools, a basic 2-level nested structure was used in which individual students (level 1) were nested within schools (level 2). For grade 12 students, the combination of both school policies and programs was not associated with the risk of smoking and the presence of the new policy was not associated with decreased risk of smoking, unless there were clear rules in place (I). For the grade 10 study, (II) schools with both policies and programs were not associated with decreased risk of smoking. However, the smoking behaviour of older students (grade 12) at a school was associated with younger students’ (grade 10) smoking behaviour. Students first enrolled in a high school in grade 9, rather than grade 10, were at increased risk of occasional smoking. For students who transitioned from grade 10 to 12 (III), close friends smoking had a substantial influence on smoking behaviour for both males and females (III). Having one or more close friends who smoke (Odds Ratio (OR) = 37.46; 95% CI = 19.39 to 72.36), one or more smokers in the home (OR = 2.35; 95% CI = 1.67 to 3.30) and seeing teachers and staff smoking on or near school property (OR=1.78; 95% CI = 1.13 to 2.80), were strongly associated with increased risk of smoking for grade 12 students. Smoking behaviour increased for both junior (Group 1) and senior (Group 2) students (IV). Group 1 students indicated a greater decrease in smoking behaviour and factors influencing smoking behaviour compared to those of Group 2. Students overestimating the percentage of youth their age who smoke was strongly associated with increased likelihood of smoking. Smoking rates showed a decreasing trend (1999, 2000, and 2001). However, policies and programs alone were not successful in influencing smoking behaviour of youth. Rather, factors within the students and schools contextual environment influenced smoking behaviour. Comprehensive approaches are required for school-based tobacco prevention interventions. Keywords: schools, policy, programs, smoking prevention, adolescents Subject Terms: school-based programming, public health, health promotion

Semi-supervised learning of WLAN radio maps

In this thesis a manifold learning method is applied to the problem of WLAN positioning and automatic radio map creation. Due to the nature of WLAN signal strength measurements, a signal map created from raw measurements results in non-linear distance relations between measurement points. These signal strength vectors reside in a high-dimensioned coordinate system. With the help of the so called Isomap-algorithm the dimensionality of this map can be reduced, and thus more easily processed. By embedding position-labeled strategic key points, we can automatically adjust the mapping to match the surveyed environment. The environment is thus learned in a semi-supervised way; gathering training points and embedding them in a two-dimensional manifold gives us a rough mapping of the measured environment. After a calibration phase, where the labeled key points in the training data are used to associate coordinates in the manifold representation with geographical locations, we can perform positioning using the adjusted map. This can be achieved through a traditional supervised learning process, which in our case is a simple nearest neighbors matching of a sampled signal strength vector. We deployed this system in two locations in the Kumpula campus in Helsinki, Finland. Results indicate that positioning based on the learned radio map can achieve good accuracy, especially in hallways or other areas in the environment where the WLAN signal is constrained by obstacles such as walls.

Future chemistry teachers use of knowledge dimensions and high-order cognitive skills in pre-laboratory concept maps

This poster describes a pilot case study, which aim is to study how future chemistry teachers use knowledge dimensions and high-order cognitive skills (HOCS) in their pre-laboratory concept maps to support chemistry laboratory work. The research data consisted of 168 pre-laboratory concept maps that 29 students constructed as a part of their chemistry laboratory studies. Concept maps were analyzed by using a theory based content analysis through Anderson & Krathwohls' learning taxonomy (2001). This study implicates that novice concept mapper students use all knowledge dimensions and applying, analyzing and evaluating HOCS to support the pre-laboratory work.

Helsingin lämpösaareke ajallisena ja paikallisena ilmiönä

The urban heat island phenomenon is the most well-known all-year-round urban climate phenomenon. It occurs in summer during the daytime due to the short-wave radiation from the sun and in wintertime, through anthropogenic heat production. In summertime, the properties of the fabric of city buildings determine how much energy is stored, conducted and transmitted through the material. During night-time, when there is no incoming short-wave radiation, all fabrics of the city release the energy in form of heat back to the urban atmosphere. In wintertime anthropogenic heating of buildings and traffic deliver energy into the urban atmosphere. The initial focus of Helsinki urban heat island was on the description of the intensity of the urban heat island (Fogelberg 1973, Alestalo 1975). In this project our goal was to carry out as many measurements as possible over a large area of Helsinki to give a long term estimate of the Helsinki urban heat island. Helsinki is a city with 550 000 inhabitants and located on the north shore of Finnish Bay of the Baltic Sea. Initially, comparison studies against long-term weather station records showed that our regular, but weekly, sampling of observations adequately describe the Helsinki urban heat island. The project covered an entire seasonal cycle over the 12 months from July 2009 to June 2010. The measurements were conducted using a moving platform following microclimatological traditions. Tuesday was selected as the measuring day because it was the only weekday during the one year time span without any public holidays. Once a week, two set of measurements, in total 104, were conducted in the heterogeneous temperature conditions of Helsinki city centre. In the more homogeneous suburban areas, one set of measurements was taken every second week, to give a total of 52.The first set of measurements took place before noon, and the second 12 hours, just prior to midnight. Helsinki Kaisaniemi weather station was chosen as the reference station. This weather station is located in a large park in the city centre of Helsinki. Along the measurement route, 336 fixed points were established, and the monthly air temperature differences to Kaisaniemi were calculated to produce monthly and annual maps. The monthly air temperature differences were interpolated 21.1 km by 18.1 km horizontal grid with 100 metre resolution residual kriging method. The following independent variables for the kriging interpolation method were used: topographical height, portion of sea area, portion of trees, fraction of built-up and not built-up area, volumes of buildings, and population density. The annual mean air temperature difference gives the best representation of the Helsinki urban heat island effect- Due to natural variability of weather conditions during the measurement campaign care must be taken when interpretation the results for the monthly values. The main results of this urban heat island research project are: a) The city centre of Helsinki is warmer than its surroundings, both on a monthly main basis, and for the annual mean, however, there are only a few grid points, 46 out of 38 191, which display a temperature difference of more than 1K. b) If the monthly spatial variation is air temperature differences is small, then usually the temperature difference between the city and the surroundings is also small. c) Isolated large buildings and suburban centres create their own individual heat island. d) The topographical influence on air temperature can generally be neglected for the monthly mean, but can be strong under certain weather conditions.