Structural Studies on the Second Mycobacterium smegmatis Dps: Invariant and Variable Features of Structure, Assembly and Function

A second DNA binding protein from stationary-phase cells of Mycobacterium smegmatis (MsDps2) has been identified from the bacterial genome. It was cloned, expressed and characterised and its crystal structure was determined. The core dodecameric structure of MsDps2 is the same as that of the Dps from the organism described earlier (MsDps1). However, MsDps2 possesses a long N-terminal tail instead of the C-terminal tail in MsDps1. This tail appears to be involved in DNA binding. It is also intimately involved in stabilizing the dodecamer. Partly on account of this factor, MsDps2 assembles straightway into the dodecamer, while MsDps1 does so on incubation after going through an intermediate trimeric stage. The ferroxidation centre is similar in the two proteins, while the pores leading to it exhibit some difference. The mode of sequestration of DNA in the crystalline array of molecules, as evidenced by the crystal structures, appears to be different in MsDps1 and MsDps2, highlighting the variability in the mode of Dps–DNA complexation. A sequence search led to the identification of 300 Dps molecules in bacteria with known genome sequences. Fifty bacteria contain two or more types of Dps molecules each, while 195 contain only one type. Some bacteria, notably some pathogenic ones, do not contain Dps. A sequence signature for Dps could also be derived from the analysis.

On the homogeneous and heterogeneous nucleation of some organic compounds

The conversion of a metastable phase into a thermodynamically stable phase takes place via the formation of clusters. Clusters of different sizes are formed spontaneously within the metastable mother phase, but only those larger than a certain size, called the critical size, will end up growing into a new phase. There are two types of nucleation: homogeneous, where the clusters appear in a uniform phase, and heterogeneous, when pre-existing surfaces are available and clusters form on them. The nucleation of aerosol particles from gas-phase molecules is connected not only with inorganic compounds, but also with nonvolatile organic substances found in atmosphere. The question is which ones of the myriad of organic species have the right properties and are able to participate in nucleation phenomena. This thesis discusses both homogeneous and heterogeneous nucleation, having as theoretical tool the classical nucleation theory (CNT) based on thermodynamics. Different classes of organics are investigated. The members of the first class are four dicarboxylic acids (succinic, glutaric, malonic and adipic). They can be found in both the gas and particulate phases, and represent good candidates for the aerosol formation due to their low vapor pressure and solubility. Their influence on the nucleation process has not been largely investigated in the literature and it is not fully established. The accuracy of the CNT predictions for binary water-dicarboxylic acid systems depends significantly on the good knowledge of the thermophysical properties of the organics and their aqueous solutions. A large part of the thesis is dedicated to this issue. We have shown that homogeneous and heterogeneous nucleation of succinic, glutaric and malonic acids in combination with water is unlikely to happen in atmospheric conditions. However, it seems that adipic acid could participate in the nucleation process in conditions occurring in the upper troposphere. The second class of organics is represented by n-nonane and n-propanol. Their thermophysical properties are well established, and experiments on these substances have been performed. The experimental data of binary homogeneous and heterogeneous nucleation have been compared with the theoretical predictions. Although the n-nonane - n-propanol mixture is far from being ideal, CNT seems to behave fairly well, especially when calculating the cluster composition. In the case of heterogeneous nucleation, it has been found that better characterization of the substrate - liquid interaction by means of line tension and microscopic contact angle leads to a significant improvement of the CNT prediction. Unfortunately, this can not be achieved without well defined experimental data.

Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial

Background The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and gefitinib in this setting. Methods This multicentre, international, open-label, exploratory, randomised controlled phase 2B trial (LUX-Lung 7) was done at 64 centres in 13 countries. Treatment-naive patients with stage IIIB or IV NSCLC and a common EGFR mutation (exon 19 deletion or Leu858Arg) were randomly assigned (1:1) to receive afatinib (40 mg per day) or gefitinib (250 mg per day) until disease progression, or beyond if deemed beneficial by the investigator. Randomisation, stratified by EGFR mutation type and status of brain metastases, was done centrally using a validated number generating system implemented via an interactive voice or web-based response system with a block size of four. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. Coprimary endpoints were progression-free survival by independent central review, time-to-treatment failure, and overall survival. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01466660. Findings Between Dec 13, 2011, and Aug 8, 2013, 319 patients were randomly assigned (160 to afatinib and 159 to gefitinib). Median follow-up was 27·3 months (IQR 15·3–33·9). Progression-free survival (median 11·0 months [95% CI 10·6–12·9] with afatinib vs 10·9 months [9·1–11·5] with gefitinib; hazard ratio [HR] 0·73 [95% CI 0·57–0·95], p=0·017) and time-to-treatment failure (median 13·7 months [95% CI 11·9–15·0] with afatinib vs 11·5 months [10·1–13·1] with gefitinib; HR 0·73 [95% CI 0·58–0·92], p=0·0073) were significantly longer with afatinib than with gefitinib. Overall survival data are not mature. The most common treatment-related grade 3 or 4 adverse events were diarrhoea (20 [13%] of 160 patients given afatinib vs two [1%] of 159 given gefitinib) and rash or acne (15 [9%] patients given afatinib vs five [3%] of those given gefitinib) and liver enzyme elevations (no patients given afatinib vs 14 [9%] of those given gefitinib). Serious treatment-related adverse events occurred in 17 (11%) patients in the afatinib group and seven (4%) in the gefitinib group. Ten (6%) patients in each group discontinued treatment due to drug-related adverse events. 15 (9%) fatal adverse events occurred in the afatinib group and ten (6%) in the gefitinib group. All but one of these deaths were considered unrelated to treatment; one patient in the gefitinib group died from drug-related hepatic and renal failure. Interpretation Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC compared with gefitinib, with a manageable tolerability profile. These data are potentially important for clinical decision making in this patient population.

First-Line afatinib versus chemotherapy in patients with non–small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases

Introduction Metastatic spread to the brain is common in patients with non–small cell lung cancer (NSCLC), but these patients are generally excluded from prospective clinical trials. The studies, phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations (LUX-Lung 3) and a randomized, open-label, phase III study of BIBW 2992 versus chemotherapy as first-line treatment for patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR activating mutation (LUX-Lung 6) investigated first-line afatinib versus platinum-based chemotherapy in epidermal growth factor receptor gene (EGFR) mutation-positive patients with NSCLC and included patients with brain metastases; prespecified subgroup analyses are assessed in this article. Methods For both LUX-Lung 3 and LUX-Lung 6, prespecified subgroup analyses of progression-free survival (PFS), overall survival, and objective response rate were undertaken in patients with asymptomatic brain metastases at baseline (n = 35 and n = 46, respectively). Post hoc analyses of clinical outcomes was undertaken in the combined data set (n = 81). Results In both studies, there was a trend toward improved PFS with afatinib versus chemotherapy in patients with brain metastases (LUX-Lung 3: 11.1 versus 5.4 months, hazard ratio [HR] = 0.54, p = 0.1378; LUX-Lung 6: 8.2 versus 4.7 months, HR = 0.47, p = 0.1060). The magnitude of PFS improvement with afatinib was similar to that observed in patients without brain metastases. In combined analysis, PFS was significantly improved with afatinib versus with chemotherapy in patients with brain metastases (8.2 versus 5.4 months; HR, 0.50; p = 0.0297). Afatinib significantly improved the objective response rate versus chemotherapy in patients with brain metastases. Safety findings were consistent with previous reports. Conclusions These findings lend support to the clinical activity of afatinib in EGFR mutation–positive patients with NSCLC and asymptomatic brain metastases.

Cilengitide combined with cetuximab and platinum-based chemotherapy as first-line treatment in advanced non-small-cell lung cancer (NSCLC) patients: Results of an open-label, randomized, controlled phase II study (CERTO)

Background: This multicentre, open-label, randomized, controlled phase II study evaluated cilengitide in combination with cetuximab and platinum-based chemotherapy, compared with cetuximab and chemotherapy alone, as first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods: Patients were randomized 1:1:1 to receive cetuximab plus platinum-based chemotherapy alone (control), or combined with cilengitide 2000 mg 1×/week i.v. (CIL-once) or 2×/week i.v. (CIL-twice). A protocol amendment limited enrolment to patients with epidermal growth factor receptor (EGFR) histoscore ≥200 and closed the CIL-twice arm for practical feasibility issues. Primary end point was progression-free survival (PFS; independent read); secondary end points included overall survival (OS), safety, and biomarker analyses. A comparison between the CIL-once and control arms is reported, both for the total cohorts, as well as for patients with EGFR histoscore ≥200. Results: There were 85 patients in the CIL-once group and 84 in the control group. The PFS (independent read) was 6.2 versus 5.0 months for CIL-once versus control [hazard ratio (HR) 0.72; P = 0.085]; for patients with EGFR histoscore ≥200, PFS was 6.8 versus 5.6 months, respectively (HR 0.57; P = 0.0446). Median OS was 13.6 for CIL-once versus 9.7 months for control (HR 0.81; P = 0.265). In patients with EGFR ≥200, OS was 13.2 versus 11.8 months, respectively (HR 0.95; P = 0.855). No major differences in adverse events between CIL-once and control were reported; nausea (59% versus 56%, respectively) and neutropenia (54% versus 46%, respectively) were the most frequent. There was no increased incidence of thromboembolic events or haemorrhage in cilengitide-treated patients. αvβ3 and αvβ5 expression was neither a predictive nor a prognostic indicator. Conclusions: The addition of cilengitide to cetuximab/chemotherapy indicated potential clinical activity, with a trend for PFS difference in the independent-read analysis. However, the observed inconsistencies across end points suggest additional investigations are required to substantiate a potential role of other integrin inhibitors in NSCLC treatment.

2nd ESMO Consensus Conference in Lung Cancer: Locally advanced stage III non-small-cell lung cancer

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11–12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.

Molecular line and continuum studies of the early stages of star formation

New stars form in dense interstellar clouds of gas and dust called molecular clouds. The actual sites where the process of star formation takes place are the dense clumps and cores deeply embedded in molecular clouds. The details of the star formation process are complex and not completely understood. Thus, determining the physical and chemical properties of molecular cloud cores is necessary for a better understanding of how stars are formed. Some of the main features of the origin of low-mass stars, like the Sun, are already relatively well-known, though many details of the process are still under debate. The mechanism through which high-mass stars form, on the other hand, is poorly understood. Although it is likely that the formation of high-mass stars shares many properties similar to those of low-mass stars, the very first steps of the evolutionary sequence are unclear. Observational studies of star formation are carried out particularly at infrared, submillimetre, millimetre, and radio wavelengths. Much of our knowledge about the early stages of star formation in our Milky Way galaxy is obtained through molecular spectral line and dust continuum observations. The continuum emission of cold dust is one of the best tracers of the column density of molecular hydrogen, the main constituent of molecular clouds. Consequently, dust continuum observations provide a powerful tool to map large portions across molecular clouds, and to identify the dense star-forming sites within them. Molecular line observations, on the other hand, provide information on the gas kinematics and temperature. Together, these two observational tools provide an efficient way to study the dense interstellar gas and the associated dust that form new stars. The properties of highly obscured young stars can be further examined through radio continuum observations at centimetre wavelengths. For example, radio continuum emission carries useful information on conditions in the protostar+disk interaction region where protostellar jets are launched. In this PhD thesis, we study the physical and chemical properties of dense clumps and cores in both low- and high-mass star-forming regions. The sources are mainly studied in a statistical sense, but also in more detail. In this way, we are able to examine the general characteristics of the early stages of star formation, cloud properties on large scales (such as fragmentation), and some of the initial conditions of the collapse process that leads to the formation of a star. The studies presented in this thesis are mainly based on molecular line and dust continuum observations. These are combined with archival observations at infrared wavelengths in order to study the protostellar content of the cloud cores. In addition, centimetre radio continuum emission from young stellar objects (YSOs; i.e., protostars and pre-main sequence stars) is studied in this thesis to determine their evolutionary stages. The main results of this thesis are as follows: i) filamentary and sheet-like molecular cloud structures, such as infrared dark clouds (IRDCs), are likely to be caused by supersonic turbulence but their fragmentation at the scale of cores could be due to gravo-thermal instability; ii) the core evolution in the Orion B9 star-forming region appears to be dynamic and the role played by slow ambipolar diffusion in the formation and collapse of the cores may not be significant; iii) the study of the R CrA star-forming region suggests that the centimetre radio emission properties of a YSO are likely to change with its evolutionary stage; iv) the IRDC G304.74+01.32 contains candidate high-mass starless cores which may represent the very first steps of high-mass star and star cluster formation; v) SiO outflow signatures are seen in several high-mass star-forming regions which suggest that high-mass stars form in a similar way as their low-mass counterparts, i.e., via disk accretion. The results presented in this thesis provide constraints on the initial conditions and early stages of both low- and high-mass star formation. In particular, this thesis presents several observational results on the early stages of clustered star formation, which is the dominant mode of star formation in our Galaxy.

Ethyl 6-chloro-2-[(2-chloro-7,8-dimethylquinolin-3-yl)methoxy]-4-phenylquino line-3-carboxylate

In the title compound, C30H24Cl2N2O3, the two quinoline ring systems are almost planar [maximum deviations = 0.029 (2) and 0.018 (3) angstrom] and the dihedral angle between them is 4.17 (8)degrees. The dihedral angle between the phenyl ring and its attached quinoline ring is 69.06 (13)degrees. The packing is stabilized by C-H center dot center dot center dot O, C-H center dot center dot center dot N, weak pi-pi stacking [centroid-centroid distances = 3.7985 (16) and 3.7662(17) angstrom] and C-H center dot center dot center dot pi interactions.

Basic Human Values in the Workplace

Työntekijöiden henkilökohtaisia arvoja ja niiden yhteyksiä asenteisiin ei ole juuri tutkittu. Tämän tutkimuksen tavoitteena oli selvittää, onko suomalaisessa metalliteollisuuden yrityksen henkilöstön (N=1314) arvojen rakenne S. H. Schwartzin arvoteorian mukainen. Lisäksi tutkittiin arvojen yhteyksiä organisaatiomuutosta koskeviin asenteisiin ja tiedon jakamiseen työyhteisössä. Arvomittarina käytettiin uutta 40-osioista Portrait Value Questionnairea (PVQ). Mittarin validiteetti osoitettiin ver-taamalla nyt kerätyn aineiston arvorakennetta aikaisemmalla mittarilla kerättyihin arvoteorian mukaisiin yliopisto-opiskelijoiden vastauksiin. Organisaatiomuutosta koskevien asenteiden ja tiedonjakamisen mittarit luotiin laadullisissa esitutkimuksissa. Tilastolliset analyysit osoittivat, että toimihenkilöiden ja työntekijöiden arvojen rakenteet noudattivat pääosin Schwartzin teoriaa, mutta turvallisuusarvot sijaitsivat molemmissa ryhmissä universalismin ja hyväntahtoisuuden joukossa. Universalismi ja hyväntahtoisuus ennustivat myönteistä asennetta organisaatiomuutoksia kohtaan, mutta perinteiden ja mielihyvän arvostaminen liittyivät kielteisiin muutosasenteisiin. Sosiaalisia normeja kunnioittavien eli yhdenmukaisuutta arvostavien henkilöiden muut arvot vaikuttivat muutosasenteisiin vähemmän kuin niillä, joille yhdenmukaisuus ei ollut tärkeää. Lisäksi suoriutumisarvon yhteys muutosasenteisiin oli yhdenmukaisuutta arvostavilla henkilöillä positiivinen, mutta niillä, jotka eivät arvostaneet yhdenmukaisuutta, yhteys oli negatiivinen. Itseohjautuvuutta arvostavat henkilöt pitivät työyhteisönsä tiedon jakamista heikompana, kun taas hyväntahtoisuutta ja yhdenmukaisuutta arvostavat pitivät sitä muihin nähden parempana. Suoriutumisarvo oli yhteydessä tiedonjakamiseen vain silloin, kun yhdenmukaisuus oli tärkeää. Työpaikkojen (N=19) keskiarvoja vertailtaessa havaittiin, että ne työpaikat, joissa arvostettiin paljon universalismia, hyväntahtoisuutta ja yhdenmukaisuutta sekä vähän valtaa ja suoriutumista saivat henkilöstöltään parhaat arvioinnit tiedon jakamisesta. Tutkimukseen osallistuneet henkilöt jaettiin työtehtäviensä perusteella kolmeen ammatilliseen ympäristöön: konven-tionaaliseen (mm. taloushallinto), realistiseen (mm. tuotanto) ja yrittäjämäiseen (mm. myynti). Yrittäjämäisessä ammatillisessa ympäristössä toimivat arvostivat enemmän kuin konventionaalisessa ympäristössä toimivat valtaa, itseohjautuvuutta ja suoriutumista. Realistisessa ympäristössä arvostettiin enemmän perinteitä ja mielihyvää kuin yrittäjämäisessä ympäristössä. Ryhmien väliset erot arvoissa johtuivat koulutuksesta, iästä ja sukupuolijakaumasta.

Sulkeuman ja neuvottelun ehdoilla : asiantuntija-aseman rakentuminen työelämässä

Closure and negotiation constructing professional position in working life The aim of the thesis is to analyse how professional positions are constructed in working life. A professional position refers to a formal professional membership, but also to a position at a work site. Formal jurisdiction provides resources for supporting a position, but the relations, practices and processes at the work site strongly shape it as well. Professional membership includes two gates: obtaining a professional diploma and access to a professional post. The concept of a professional position is based on two sub-concepts: legitimation and authority. Legitimation is society-level jurisdiction over professioning. Legitimation can be claimed in legislation, in the public space and the media, and at the work site. Authority requires constructing professional work territories and practicing authority in work-related decision making processes. The thesis is based on five articles which deal with the following topics: gendered professional careers; organising professional work; the impact of the social and cultural backgrounds when striving for professional positions; and models of research work. The articles represent two types of sociological research: the structural approach with quantitative methodology and the approach of micro-social analysis with qualitative methodology. The first approach was suitable for analyzing professional career formation and its social and ethnic conditions. The second approach has been applied in the articles dealing with the organization of professional work and models of research work. I have combined and analysed the results of these studies under the theoretical frame of the professional position in working life. Legislation is the most powerful form of legitimation. Professional membership is strongly regulated in disciplines where a degree requirement is defined by law. In addition, closures related to social conditions still affect professional positions, but their character is loose and changing. The closures related to social conditions are based on many mutually overlapping principles: social, cultural and ethnic backgrounds and gender. Despite the closures, professional experts have to negotiate their positions, particularly when the situation in the work sites and society changes. Professional authority is reinforced at the organizational level by legislation; when the institutional status of a public sector professional organization is defined by law, it reinforces the professional position of the employees. In the business line of new media, the employees need to negotiate with the management, other professional groups and clients when striving for reinforce their professional position.

Analysis of shore line protection works in tsunami hit areas of east coast of India

Evaluation and design of shore protection works in the case of tsunamis assumes considerable importance in view of the impact it had in the recent tsunami of 26th December 2004 in India and other countries in Asia. The fact that there are no proper guidelines have made in the matters worse and resulted in the magnitude of damage that occurred. Survey of the damages indicated that the scour as a result of high velocities is one of the prime reasons for damages in the case of simple structures. It is revealed that sea walls in some cases have been helpful to minimize the damages. The objective of this paper is to suggest that design of shore line protection systems using expected wave heights that get generated and use of flexible systems such as geocells is likely to give a better protection. The protection systems can be designed to withstand the wave forces that corresponding to different probabilities of incidence. A design approach of geocells protection system is suggested and illustrated with reference to the data of wave heights in the east coast of India.

Support vector machine approach for the switching transient peak overvoltages during line energization

At the time of restoration transmission line switching is one of the major causes, which creates transient overvoltages. Though detailed Electro Magnetic Transient studies are carried out extensively for the planning and design of transmission systems, such studies are not common in a day-today operation of power systems. However it is important for the operator to ensure during restoration of supply that peak overvoltages resulting from the switching operations are well within safe limits. This paper presents a support vector machine approach to classify the various cases of line energization in the category of safe or unsafe based upon the peak value of overvoltage at the receiving end of line. Operator can define the threshold value of voltage to assign the data pattern in either of the class. For illustration of proposed approach the power system used for switching transient peak overvoltages tests is a 400 kV equivalent system of an Indian southern gri

Itämafia : Uhkakuvapolitiikka, rikosilmiöt ja kulttuuriset merkitykset

The Eastern Mafia Threat policy, crime phenomena, and cultural meanings An interdisciplinary research on the crime phenomena and the threat policy relating to the organized crime and the mafia of Russia and Estonia is based on 151 expert interviews, statistics, documents, research literature, and press material. The main part of the material consists of interviews of the Finnish, Estonian and Russian police authorities specialized in the problem of organized crime, and the reports on the crime situation drawn up in the Finnish diplomatic representations in Tallinn and St Petersburg. The interviews have been gathered in the years 1996-2001. The main theoretical tools of the research are constructivist research on social problems, and political psychology. Definitional processes of social problems and cultural semantic structures behind them are identified in the analysis and connected to the analysis of the crime cases. Both in the Anglo-American and Russian cultural frames there appears an inflated and exaggerated talk, according to which the mafia rules everything in Russia and is spreading everywhere. There is the traditional anti-Semitic paranoia in the core of this cultural symbiosis produced by Russian legal nihilism, the theory of totalitarianism of Sovietology, and the inertia of Russian anti-capitalism. To equate the Sicilian Mafia with Russia is an anachronism, since no empirical proof of systematic uncontrolled violence or absolute power vacuum in Russia can be found. In the Anglo-American policy of threat images, "the Russian mafia" was seen as a commodified conspiracy theory, which the police, the media, and the research took advantage of, blurring the line between fact and fiction. In Finland, the evolution of the policy of threat images proceeded in three phases: Initially, extensive rolling of refugees and criminals from Russia to Finland was emphasized in the beginning of the 1990's. In the second phase, the eastern mafia was said to infiltrate all over Finnish society and administration. Finland was, however, found immune to this kind of spreading. In the third phase, in the 21st century, the organized crime of Finland was said to be lead from abroad. In Finland, the policy of threat images was especially canalised to moral panics connected to "eastern prostitution". In Estonia, the policy of threat images emphasized the crime organized by the Russian authorities and politicians in order to weaken Estonia. In Russia, the policy of threat images emphasized the total criminalizing of society caused by criminal capitalism. In every country, the policy of threat images was affected by a so-called large-group identity, a term by Vamik Volkan, in which a so-called chosen trauma caused a political paranoia of an outer and inner danger. In Finland, procuring, car theft, and narcotics crimes were at their widest arranged by the Finnish often with the help of the Estonians. The Russians had no influence in the most serious violent crimes in Finland, although the number of assassinations were at least 5, 000 in Russia in the 1990's. In Russia, the assassinations were on one hand connected to marital problems, on the other hand to the pursuit of public attention and a hoped-for effect by the aid of the murder of an influential person. In the white-collar crime phenomena between Finland and Russia, the Finnish state and Finnish corporations gained remarkable benefit of the frauds aimed at the states of the Soviet Union and Russia in 1980's-21st century. The situation of Estonia was very difficult compared to that of Russia in the 1990's, which was manifested in the stagnation of the Estonian police and judicial authorities, the crimes of the police and the voluntary paramilitary organization, bomb explosions, the rebellion called "the jaeger crisis" in the voluntary paramilitary organization, and the "blood autumn" of Eastern Virumaa, in other words terror. The situation of Estonia had a powerful effect on the crime situation of Finland and on the security of the Finnish diplomats. In the continuum of the Finnish policy of threat images, Russia and the Russians were, however, presented as a source of a marked danger.

NMR study of internal motions in certain iron group fluosilicates

NMR study of ferrous fluosilicate hexahydrate indicated the presence of motion of both proton and fluorine nuclei. Only a single narrow line was observed for protons for any arbitrary orientation of a single crystal with respect to the applied magnetic field. This can be interpreted in terms of a phase-correlated flip motion of the interproton vectors between two disordered orientations or in terms of a hindered rotation of the Fe(H2O) 6 octahedron about the fourfold axes, together with the flip motion. The fluorine second moment indicated that the SiF6 octahedron also is undergoing reorientation. The temperature variation of the powder linewidth showed a transition around 195°K and led to rather low values for the potential barriers hindering the motions. No significant temperature variation of the linewidth was observed for hexahydrated cobalt fluosilicate in the temperature range between 90°K and room temperature. Similar observations in a powder sample of tetrahydrated copper fluosilicate also showed the presence of internal motions. The linewidth transition in this case took place at about 220°K and was found to be rather abrupt. The potential barrier for the motion was found to be relatively high.

Data integration from two microarray platforms identifies bi-allelic genetic inactivation of RIC8A in a breast cancer cell line

Background: Using array comparative genomic hybridization (aCGH), a large number of deleted genomic regions have been identified in human cancers. However, subsequent efforts to identify target genes selected for inactivation in these regions have often been challenging. Methods: We integrated here genome-wide copy number data with gene expression data and non-sense mediated mRNA decay rates in breast cancer cell lines to prioritize gene candidates that are likely to be tumour suppressor genes inactivated by bi-allelic genetic events. The candidates were sequenced to identify potential mutations. Results: This integrated genomic approach led to the identification of RIC8A at 11p15 as a putative candidate target gene for the genomic deletion in the ZR-75-1 breast cancer cell line. We identified a truncating mutation in this cell line, leading to loss of expression and rapid decay of the transcript. We screened 127 breast cancers for RIC8A mutations, but did not find any pathogenic mutations. No promoter hypermethylation in these tumours was detected either. However, analysis of gene expression data from breast tumours identified a small group of aggressive tumours that displayed low levels of RIC8A transcripts. qRT-PCR analysis of 38 breast tumours showed a strong association between low RIC8A expression and the presence of TP53 mutations (P = 0.006). Conclusion: We demonstrate a data integration strategy leading to the identification of RIC8A as a gene undergoing a classical double-hit genetic inactivation in a breast cancer cell line, as well as in vivo evidence of loss of RIC8A expression in a subgroup of aggressive TP53 mutant breast cancers.