Nuclear Matrix in Apoptotic Cell Death and Cell Proliferation. The role of Nuclear Mitotic Apparatus (NuMA) Protein

The nucleus is a membrane enclosed organelle containing most of the genetic information of the cell in the form of chromatin. The nucleus, which can be divided into many sub-organelles such as the nucleoli, the Cajal bodies and the nuclear lamina, is the site for several essential cellular functions such as the DNA replication and its regulation and most of the RNA synthesis and processing. The nucleus is often affected in disease: the size and the shape of the nucleus, the chromatin distribution and the size of the nucleoli have remained the basis for the grading of several cancers. The maintenance of the vertebrate body shape depends on the skeleton. Similarly, in a smaller context, the shape of the cell and the nucleus are mainly regulated by the cytoskeletal and nucleoskeletal elements. The nuclear matrix, which by definition is a detergent, DNase and salt resistant proteinaceous nuclear structure, has been suggested to form the nucleoskeleton responsible for the nuclear integrity. Nuclear mitotic apparatus protein, NuMA, a component of the nuclear matrix, is better known for its mitotic spindle organizing function. NuMA is one of the nuclear matrix proteins suggested to participate in the maintenance of the nuclear integrity during interphase but its interphase function has not been solved to date. This thesis study concentrated on the role of NuMA and the nuclear matrix as structural and functional components of the interphase nucleus. The first two studies clarified the essential role of caspase-3 in the disintegration of the nuclear structures during apoptosis. The second study also showed NuMA and chromatin to co-elute from cells in significant amounts and the apoptotic cleavage of NuMA was clarified to have an important role in the dissociation of NuMA from the chromatin. The third study concentrated on the interphase function of NuMA showing NuMA depletion to result in cell cycle arrest and the cytoplasmic relocalization of NuMA interaction partner GAS41. We suggest that the relocalization of the transcription factor GAS41 may mediate the cell cycle arrest. Thus, this study has given new aspects in the interactions of NuMA, chromatin and the nuclear matrix.

Nuclear magnetic resonance investigation of structure and dynamics of some electrolyte solutions

Electrolyte solutions are of importance in a wide range of scientific contexts and as such have attracted considerable theoretical and experimental effort over many years. Nuclear Magnetic resonance provides a precise and versatile tool for investigation of electrolyte solutions, both in water and in organic solvents. Many structural and dynamic properties can be obtained through NMR experiments. The solution of aluminum chloride in water was studied. Different concentrations were taken for investigation. Independence of maximum line shift from concentration and acidity was shown. Six-coordinated structure of solvation shell was confirmed by experiments on 'H and 27A1 nuclei. Diffusion coefficients were studied. The solution of nickel chloride in methanol was studied. Lines, corresponding to coordinated and bulk methanol were found. Four-, five- and six-coordinated structures were found in different temperatures. The line for coordinated -OD group of deuterated methanol was observed on 2H spectrum for the first time. Partial deuteration of CH3 group was detected. Inability to observe coordinated -OH group was explained.

Investigations of GaAs based heterostructures for spintronics

In the present work are reported investigations of structural, magnetic and electronic properties of GaAs/Ga1-xInxAs/GaAs quantum wells (QW) having a 0.5 - 1.8 monolayer thick Mn layer, separated from the quantum well by a 3 nm thick spacer. The structure of the samples is analyzed in details by photoluminescence and high-resolution X-ray difractometry and reflectometry, confirming that Mn atoms are practically absent from the QW. Transport properties and crystal structure are analyzed for the first time for this type of QW structures with so high mobility. Observedconductivity and the Hall effect in quantizing magnetic fields in wide temperature range, defined by transport of holes in the quantum well, demonstrate properties inherent to ferromagnetic systems with spin polarization of charge carriersin the QW. Investigation of the Shubnikov ¿ de Haas and the Hall effects gave the possibility to estimate the energy band parameters such as cyclotron mass andFermi level and calculate concentrations and mobilities of holes and show the high-quality of structures. Magnetic ordering is confirmed by the existence of the anomalous Hall effect.

The probabilistic risk analysis of external hazards of an interim storage for spent nuclear fuel

Tässä diplomityössä tehtiin Olkiluodon ydinvoimalaitoksella sijaitsevan käytetyn ydinpolttoaineen allasvarastointiin perustuvan välivaraston todennäköisyysperustainen ulkoisten uhkien riskianalyysi. Todennäköisyysperustainen riskianalyysi (PRA) on yleisesti käytetty riskien tunnistus- ja lähestymistapa ydinvoimalaitoksella. Työn tarkoituksena oli laatia täysin uusi ulkoisten uhkien PRA-analyysi, koska Suomessa ei ole aiemmin tehty vastaavanlaisia tämän tutkimusalueen riskitarkasteluja. Riskitarkastelun motiivina ovat myös maailmalla tapahtuneiden luonnonkatastrofien vuoksi korostunut ulkoisten uhkien rooli käytetyn ydinpolttoaineen välivarastoinnin turvallisuudessa. PRA analyysin rakenne pohjautui tutkimuksen alussa luotuun metodologiaan. Analyysi perustuu mahdollisten ulkoisten uhkien tunnistamiseen pois lukien ihmisen aikaansaamat tahalliset vahingot. Tunnistettujen ulkoisten uhkien esiintymistaajuuksien ja vahingoittamispotentiaalin perusteella ulkoiset uhat joko karsittiin pois tutkimuksessa määriteltyjen karsintakriteerien avulla tai analysoitiin tarkemmin. Tutkimustulosten perusteella voitiin todeta, että tiedot hyvin harvoin tapahtuvista ulkoisista uhista ovat epätäydellisiä. Suurinta osaa näistä hyvin harvoin tapahtuvista ulkoisista uhista ei ole koskaan esiintynyt eikä todennäköisesti koskaan tule esiintymään Olkiluodon vaikutusalueella tai edes Suomessa. Esimerkiksi salaman iskujen ja öljyaltistuksen roolit ja vaikutukset erilaisten komponenttien käytettävyyteen ovat epävarmasti tunnettuja. Tutkimuksen tuloksia voidaan pitää kokonaisuudessaan merkittävinä, koska niiden perusteella voidaan osoittaa ne ulkoiset uhat, joiden vaikutuksia olisi syytä tutkia tarkemmin. Yksityiskohtaisempi tietoisuus hyvin harvoin esiintyvistä ulkoisista uhista tarkentaisi alkutapahtumataajuuksien estimaatteja.

How (not) to interview children : interviews with young children in sexual abuse investigations in Finland

The present thesis had two main objectives: The first was to assess how child sexual abuse (CSA) interviews in Finland are conducted through analysing the interviewing techniques applied and the language used by the interviewers, as well as to suggest ways to improve interviews if they were found to have deficiencies. The second main aim was to contribute to the growing research corpus concerning CSA interviews, in particular, by addressing how interviewers follow up information provided by the child, by analysing whether child health care professionals would use childadapted language, and by studying the kind of modifications in the verbal behaviour of interviewers and children that were associated with a) repeated interviews, b) a support person’s presence at the interview, and c) the use of anatomically detailed dolls. Two complementary samples of CSA interviews were analysed. The first one was composed of child interviews with 3-12-year-old children (N = 27) that had been considered problematic by lawyers or other involved professionals (Studies I and IV). The second sample consisted of unselected interviews (N = 43) with children aged 3 to 8 years conducted in a number of hospitals in different parts of the country (Studies II and III). Study I: The verbal interaction between interviewer and child was analysed in a sample of interviews that had been considered to be problematic by involved professionals. Results showed that interviewers used inappropriate questioning techniques, relying on option-posing, specific suggestive and unspecific suggestive questions to a significant extent, these comprising around 50% of all interviewer utterances. The proportion of invitations, which the research community recommends interviewers to rely on, was strikingly low. Invitations and directive utterances were associated with an increase in informative responses by the child in terms of response type, number of new details reported, as well as length of response. The opposite was true for option-posing and suggestive utterances. Longer questions by the interviewer (in number of words) often rendered no reply from the child, whereas shorter questions were followed by descriptive answers. Even after the child had provided an informative answer, interviewers failed to follow up the information in an adequate way and instead continued to rely on focused and leading questions. Study II: Due to the possible bias of the sample analysed in Study I, the most important analyses were rerun with the unselected sample and reported separately. Results were quite similar between the two studies, indicating that the problems observed in Study I, with interviewers relying on option-posing and suggestive questions to a significant extent, are likely to be general and not specific for those interviews. Even if suggestive questions were slightly less and invitations slightly more common in this sample than in the previous study, almost half of the interviewer questions were still optionposing or suggestive, and also in this sample, interviewers failed to follow up information by the child in a facilitating manner. Differentiating between judicial and contextual details showed that while facilitators, invitations, and directive utterances elicited more contextual than judicial details, the opposite was true for specific suggestive utterances. These results might be explained by the reluctance of children to describe sexual details related to the abuse events. Alternatively, they may also be due to children describing incorrect sexual details as a result of suggestive interviewing techniques. Study III: This study examined features of the language used by the interviewers. Interviewer utterances included multiple questions, long statements, complicated grammar and concepts, as well as unclear references to persons and situations. More than a fifth of the interviewer utterances were coded as belonging to at least one of these categories. The results suggest that even professionals who are experienced in interacting with children may have difficulties in using a child-sensitive language, adding to the pool of studies showing similar problems to occur in legal hearings with children conducted by lawyers. As children rarely comment on, or even recognise, their lack of comprehension, the use of a language that is too complex can have detrimental consequences for the outcomes of investigative interviews. Interviewers used different approaches to introduce the topic of abuse. While 15% of the children spontaneously addressed the topic of abuse, probably indicating that they felt confident with the interviewer and the situation, in almost 50% of the cases, the interviewer introduced the topic of abuse in a way that can be considered leading. Interviews were characterised by a lack of structure, apparent in frequent rapid switches of topic by the interviewer. This manner was associated with a decrease in the number of new details provided by the children. Study IV: This study analysed possible changes in the interview dynamics associated with repeated interviewing, the presence of a support person (related to the child), and the use of anatomically detailed (AD) dolls. Repeated interviewing, in combination with suggestive questions, has previously been found to seriously contaminate children’s accounts. In the present material, interviewers used significantly more suggestive utterances in the repeated condition, thus endangering the reliability of the children’s reports. Few studies have investigated the effects of a support person’s presence at the interview. The results of the present study showed that interviewers talked more and children provided less information when a support person was present. Supporting some earlier findings regarding the use of AD dolls, the present results showed that using AD dolls was associated with longer interviewer utterances and shorter, less responsive, and less detailed child responses. Interviewers used up to five times more unspecific suggestive utterances when dolls were used, for instance through repeatedly asking the child to show “what really happened” with the dolls. Conclusion: The results indicate that CSA interviews in Finland are not conducted in a manner that follows best practice as defined by the research community and as stated in a number of guidelines. When comparing these questioning strategies with the recommendations, which have been predominant in the field for more than ten years now, it can be concluded that the interviews analysed were conducted in a manner that undermines the possibility to elicit an uncontaminated and accurate narrative from the children. A particularly worrying finding was the fact that interviewers did not follow up relevant information by the children in an adequate way. A number of clinical implications can be drawn from the results, particularly concerning the need for improvement in the quality of CSA interviews. There is convincing research regarding how to improve CSA interviews, notably through training forensic child interviewers to use a structured interviewing protocol, and providing them with continuous supervision and feedback. Allocating appropriate resources to improve the quality of forensic child interviews is a matter of protecting the rights of all persons involved in CSA investigations, in particular those of the children.

Structure-related magnetic fabric studies : implications for deformed and undeformed Precambrian rocks

The aim of this thesis research was to gain a better understanding of the emplacement of rapakivi granite intrusions, as well as the emplacement of gold-bearing hydrothermal fluids in structurally controlled mineralizations. Based on investigations of the magnetic fabric, the internal structures could be analysed and the intrusion mechanisms for rapakivi granite intrusions and respectively different deformation stages within gold-bearing shear and fault zones identified. Aeromagnetic images revealed circular structures within the rapakivi granite batholiths of Wiborg, Vehmaa and Åland. These circular structures represent intrusions that eventually build up these large batholiths. The rapakivi granite intrusions of Vehmaa, Ruotsinpyhtää within the Wiborg batholith and Saltvik intrusions within the Åland batholith all show bimodal magnetic susceptibilities with paramagnetic and ferromagnetic components. The distribution of the bimodality is related to different magma batches of the studied intrusions. The anisotropy of magnetic susceptibility (AMS) reveals internal structures that cannot be studied macroscopically or by microscope. The Ruotsinpyhtää and Vehmaa intrusions represent similar intrusion geometries, with gently to moderately outward dipping magnetic foliations. In the case of Vehmaa, the magnetic lineations are gently plunging and trend in the directions of the slightly elongated intrusion. The magnetic lineations represent magma flow. The shapes of the AMS ellipsoids are also more planar (oblate) in the central part of the intrusion, whereas they become more linear (prolate) near the margin. These AMS results, together with field observations, indicate that the main intrusion mechanism has involved the subsidence of older blocks with successive intrusion of fractionated magma during repeated cauldron subsidence. The Saltvik area within the Åland batholith consists of a number of smaller elliptical intrusions of different rapakivi types forming a multiple intrusive complex. The magnetic fabric shows a general westward dipping of the pyterlite and eastward dipping of the contiguous even-grained rapakivi granite, which indicates a central inflow of magma batches towards the east and west resulting from a laccolitic emplacement of magma batches, while the main mechanism for space creation was derived from subsidence. The magnetic fabric of structurally controlled gold potential shear and fault zones in Jokisivu, Satulinmäki and Koijärvi was investigated in order to describe the internal structures and define the deformation history and emplacement of hydrothermal fluids. A further aim of the research was to combine AMS studies with palaeomagnetic methods to constrain the timing for the shearing event relative to the precipitation of ferromagnetic minerals and gold. All of the studied formations are dominated by monoclinic pyrrhotite. The AMS directions generally follow the tectonic structures within the formations. However, internal variations in the AMS direction as well as the shapes of the AMS ellipsoids are observed within the shear zones. In Jokisivu and Satulinmäki in particular, the magnetic signatures of the shear zone core differ from the margins. Furthermore, the shape of the magnetic fabric in the shear zone core of Jokisivu is dominated by oblate shapes, whereas the margins exhibit prolate shapes. These variations indicate a later effect of the hydrothermal fluids on the general shear event. The palaeo-magnetic results reveal a deflection from the original Svecofennian age geomagnetic direction. These results, coupled with correlations between the orientation of the NRM vectors and the magnetic and rock fabrics, imply that the gold-rich hydrothermal fluids were emplaced pre/syntectonically during the late stages of the Svecofennian orogeny.

Dynamical and Chemical Structure of Galactic Halos

This doctoral dissertation presents studies of the formation and evolution of galaxies, through observations and simulations of galactic halos. The halo is the component of galaxies which hosts some of the oldest objects we know of in the cosmos; it is where clues to the history of galaxies are found, for example, by how the chemical structure is related to the dynamics of objects in the halo. The dynamical and chemical structure of halos, both in the Milky Way’s own halo, and in two elliptical galaxies, is the underlying theme in the research. I focus on the density falloff and chemistry of the two external halos, and on the dynamics, density falloff, and chemistry of the Milky Way halo. I first study galactic halos via computer simulations, to test the long- term stability of an anomalous feature recently found in kinematics of the Milky Way’s metal-poor stellar halo. I find that the feature is transient, making its origin unclear. I use a second set of simulations to test if an initially strong relation between the dynamics and chemistry of halo glob-ular clusters in a Milky Way-type galaxy is affected by a merging satellite galaxy, and find that the relation remains strong despite a merger in which the satellite is a third of the mass of the host galaxy. From simulations, I move to observing halos in nearby galaxies, a challenging procedure as most of the light from galaxies comes from the disk and bulge components as opposed to the halo. I use Hubble Space Tele scope observations of the halo of the galaxy M87 and, comparing to similar observations of NGC 5128, find that the chemical structure of the inner halo is similar for both of these giant elliptical galaxies. I use Very Large Telescope observations of the outer halo of NGC 5128 (Centaurus A) and, because of the difficultly in resolving dim extragalac- tic stellar halo populations, I introduce a new technique to subtract the contaminating background galaxies. A transition from a metal-rich stellar halo to a metal-poor has previously been discovered in two different types of galaxies, the disk galaxy M31 and the classic elliptical NGC 3379. Unexpectedly, I discover in this third type of galaxy, the merger remnant NGC 5128, that the density of metal-rich and metal-poor halo stars falls at the same rate within the galactocentric radii of 8 − 65 kpc, the limit of our observations. This thesis presents new results which open opportunities for future investigations.