Reconstitution of the strand invasion step of double-strand break repair using human Rad51 Rad52 and RPA proteins.

The human Rad51 recombinase is essential for the repair of double-strand breaks in DNA that occur in somatic cells after exposure to ionising irradiation, or in germ line cells undergoing meiotic recombination. The initiation of double-strand break repair is thought to involve resection of the double-strand break to produce 3'-ended single-stranded (ss) tails that invade homologous duplex DNA. Here, we have used purified proteins to set up a defined in vitro system for the initial strand invasion step of double-strand break repair. We show that (i) hRad51 binds to the ssDNA of tailed duplex DNA molecules, and (ii) hRad51 catalyses the invasion of tailed duplex DNA into homologous covalently closed DNA. Invasion is stimulated by the single-strand DNA binding protein RPA, and by the hRad52 protein. Strikingly, hRad51 forms terminal nucleoprotein filaments on either 3' or 5'-ssDNA tails and promotes strand invasion without regard for the polarity of the tail. Taken together, these results show that hRad51 is recruited to regions of ssDNA occurring at resected double-strand breaks, and that hRad51 shows no intrinsic polarity preference at the strand invasion step that initiates double-strand break repair.

MRE11-RAD50-NBS1 is a critical regulator of FANCD2 stability and function during DNA double-strand break repair.

Monoubiquitination of the Fanconi anaemia protein FANCD2 is a key event leading to repair of interstrand cross-links. It was reported earlier that FANCD2 co-localizes with NBS1. However, the functional connection between FANCD2 and MRE11 is poorly understood. In this study, we show that inhibition of MRE11, NBS1 or RAD50 leads to a destabilization of FANCD2. FANCD2 accumulated from mid-S to G2 phase within sites containing single-stranded DNA (ssDNA) intermediates, or at sites of DNA damage, such as those created by restriction endonucleases and laser irradiation. Purified FANCD2, a ring-like particle by electron microscopy, preferentially bound ssDNA over various DNA substrates. Inhibition of MRE11 nuclease activity by Mirin decreased the number of FANCD2 foci formed in vivo. We propose that FANCD2 binds to ssDNA arising from MRE11-processed DNA double-strand breaks. Our data establish MRN as a crucial regulator of FANCD2 stability and function in the DNA damage response.

Olanzapine or chlorpromazine plus lithium in first episode psychotic mania: An 8-week randomised controlled trial.

BACKGROUND: Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments. METHODS: Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures. RESULTS: Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate (P=.032) and earlier occurrence (P=.043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons. CONCLUSIONS: Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample.

Large Break Blowdown Test Facility Study

Työn tarkoituksena on kerätä yhteen tiedot kaikista maailmalta löytyvistä ison LOCA:n ulospuhallusvaiheen tutkimiseen käytetyistä koelaitteistoista. Työn tarkoituksena on myös antaa pohjaa päätökselle, onko tarpeellista rakentaa uusi koelaitteisto nesterakenne-vuorovaikutuskoodien laskennan validoimista varten. Ennen varsinaisen koelaitteiston rakentamista olisi tarkoituksenmukaista myös rakentaa pienempi pilottikoelaitteisto, jolla voitaisiin testata käytettäviä mittausmenetelmiä. Sopivaa mittausdataa tarvitaan uusien CFD-koodien ja rakenneanalyysikoodien kytketyn laskennan validoimisessa. Näitä koodeja voidaan käyttää esimerkiksi arvioitaessa reaktorin sisäosien rakenteellista kestävyyttä ison LOCA:n ulospuhallusvaiheen aikana. Raportti keskittyy maailmalta löytyviin koelaitteistoihin, uuden koelaitteiston suunnitteluperusteisiin sekä aiheeseen liittyviin yleisiin asioihin. Raportti ei korvaa olemassa olevia validointimatriiseja, mutta sitä voi käyttää apuna etsittäessä validointitarkoituksiin sopivaa ison LOCA:n ulospuhallusvaiheen koelaitteistoa.

Maladaptive emotion regulation strategies and stress sensitivity mediate the relation between adverse life events and attenuated positive psychotic symptoms.

INTRODUCTION: There is now solid evidence for a relation between adverse life events (ALE) and psychotic symptoms in patients with psychosis and in the general population. A recent study has shown that this relation may be partially mediated by stress sensitivity, suggesting the influence of other factors. The aim of this study was to assess the mediation effect of emotion regulation strategies and stress sensitivity in the relation between ALE and attenuated positive psychotic symptoms (APPS) in the general population. METHODS: Hundred and twelve healthy volunteers were evaluated with measures of APPS, emotion regulation strategies, ALE and stress sensitivity. RESULTS: Results demonstrated that the relation between ALE, hallucination and delusion proneness was completely mediated by maladaptive emotion regulation strategies, but not by stress sensitivity. However, in addition to maladaptive emotion regulation strategies, stress sensitivity demonstrated a mediation effect between ALE and attenuated positive psychotic positive symptoms when positive psychotic symptoms were grouped together. CONCLUSIONS: There are probably several possible trajectories leading to the formation of positive psychotic symptoms and the results of the present study reveal that one such trajectory may involve the maladaptive regulation of negative emotions alongside a certain general vulnerability after experiencing ALE.

Trajectory and predictors of quality of life in first episode psychotic mania.

BACKGROUND: Little is known about the trajectory of quality of life (QoL) following a first episode of psychotic mania in bipolar disorder (BD). This 18-month longitudinal study investigated the trajectory of QoL, and the influence of premorbid adjustment and symptoms on 18-month QoL in a cohort of young people experiencing a first episode of psychotic mania. METHODS: As part of an overarching clinical trial, at baseline, sixty participants presenting with a first episode of psychotic mania (BD Type 1 - DSM-IV) completed symptomatic and functional assessments in addition to the Premorbid Adjustment Scale - General Subscale. Symptom measures were repeated at 18-month follow up. QoL was rated using the Quality of Life Scale (QLS) at designated time points. RESULTS: Mean QLS scores at initial measurement (8 weeks) were 61% of the maximum possible score, increasing significantly to 70% at 12 months, and 71.2% at 18-month follow-up. Premorbid adjustment and 18-month depressive symptoms were significantly associated with QoL at 18-month follow-up. LIMITATIONS: Study limitations include the small sample size, inclusion of participants with psychotic mania only, use of measures originally designed for use with schizophrenia spectrum disorders, and lack of premorbid or baseline measurement of QoL. CONCLUSIONS: Results suggest that QoL can be maintained early in BD, and reinforce the importance of assertively treating depressive symptoms throughout the course of this disorder. The emergence of a link between premorbid adjustment and poorer QoL in this cohort highlights the importance of assessing facets of adjustment when planning psychological interventions.

Essolube Break-In Oil (kuntoonajoöljy)

kuv., 10 x 14 cm

Essolube break-in oil kuntoonajoöljy

10 x 15 cm

Essolube break-in oil kuntoonajoöljy

kuv., 10 x 15 cm

Essolube break-in oil inköringsolja

kuv., 10 x 15 cm

Evaluation of Bubble Formation and Break Up in Suppression Pools by Using Pattern Recognition Methods

During a possible loss of coolant accident in BWRs, a large amount of steam will be released from the reactor pressure vessel to the suppression pool. Steam will be condensed into the suppression pool causing dynamic and structural loads to the pool. The formation and break up of bubbles can be measured by visual observation using a suitable pattern recognition algorithm. The aim of this study was to improve the preliminary pattern recognition algorithm, developed by Vesa Tanskanen in his doctoral dissertation, by using MATLAB. Video material from the PPOOLEX test facility, recorded during thermal stratification and mixing experiments, was used as a reference in the development of the algorithm. The developed algorithm consists of two parts: the pattern recognition of the bubbles and the analysis of recognized bubble images. The bubble recognition works well, but some errors will appear due to the complex structure of the pool. The results of the image analysis were reasonable. The volume and the surface area of the bubbles were not evaluated. Chugging frequencies calculated by using FFT fitted well into the results of oscillation frequencies measured in the experiments. The pattern recognition algorithm works in the conditions it is designed for. If the measurement configuration will be changed, some modifications have to be done. Numerous improvements are proposed for the future 3D equipment.

Analysis of PACTEL small break LOCA experiment using TRACE

A small break loss-of-coolant accident (SBLOCA) is one of problems investigated in an NPP operation. Such accident can be analyzed using an experiment facility and TRACE thermal-hydraulic system code. A series of SBLOCA experiments was carried out on Parallel Channel Test Loop (PACTEL) facility, exploited together with Technical Research Centre of Finland VTT Energy and Lappeenranta University of Technology (LUT), in order to investigate two-phase phenomena related to a VVER-type reactor. The experiments and a TRACE model of the PACTEL facility are described in the paper. In addition, there is the TRACE code description with main field equations. At the work, calculations of a SBLOCA series are implemented and after the calculations, the thesis discusses the validation of TRACE and concludes with an assessment of the usefulness and accuracy of the code in calculating small breaks.