An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Arkaismi, konteksti ja kirjuri:sananloppuisen <em>k</em>:n merkintä Christfrid Gananderin kansanrunokokoelmassa

Abstract In my study, I am using methods of text criticism to analyse how Chrisfrid Ganander (1741–1790) marked the word-final k in the Kalevala-metre old poems that he recorded in his dictionary and in Mythologia Fennica. These poems were published in the XV part of the Ancient Poems of the Finnish People. My study is linked to folkloristics, but belongs principally to the field of research into Old Literary Finnish. In my philological analysis I am comparing Ganander’s poetic texts with other old texts in the Kalevala-metre and analysing their relations and the origins and history of the texts. I am interpreting the phonetic and morphologic structure of the poems with the help of the context and on the cultural historical basis of the texts. The results of my study would seem to indicate that Ganander marked the final k clearly more frequently than his other contemporaries. In earlier studies Ganander’s marking of the final k has been criticized for inconsistency. In fact, in my data, the occurrences of the word-final k are not morphologically regular in the sense that the final k would always systematically occur in, e.g., imperatives. However, a regular pattern can be found in the way in which the cases with a final k fit the general ideas about the occurrence of the final k. Nevertheless, my data also include a few extraordinary occurrences of the final k and even some cases that may be deemed erroneous. The irregularities in the marking can be explained by the fact that Ganander had several different text versions of the same poem. The way in which Ganander marked the final k seems to have been affected mostly by the source texts and locality of the verses; their morphology, phonetic environment, and verse type. Yet, Ganander seems to have even used the final k deliberately in some cases. This is evident from a few cases of the final k in the texts Ganander produced himself and certain results of my philological analysis. The essential is that Ganander marked his final k’s in places where they could be expected from a historical perspective. Thus, it seems that he had an idea of where the final k’s should be. Ganander seems to have followed the marking of the final k’s in his sources very faithfully. However, it is especially interesting that he also marked the final k’s in verses based on source texts where the final k’s had not been marked. Ganander may have had old notes about these poems in his possession that the others did not have access to or that were not preserved in their collections. These verses might even represent poetry collected by Ganander himself. It seems that Ganander managed to catch and record rare and old linguistic material that has not, in fact, been preserved anywhere else. As a philologist, Ganander was versatile, critical, and enlightened, but he also made up some of his analyses purely on the basis of poetic verses. His dictionary includes even erroneous and incoherent interpretations. Ganander’s dictionary quotations that are based on folklore texts may also seem imaginative in the sense that he was trying to explain the world of folk poetry in them. Ganander’s philological interpretations – including their errors – have left their mark on later literary works. Thus, the poetic language as it was recorded by Ganander has affected the description of the Finnish language in dictionaries and grammars. The study and analysis of the language in the folk poems may therefore shed light on the history of the scientific description of the Finnish language.Tiivistelmä Tarkastelen tutkimuksessani tekstikriittisin menetelmin, miten Chrisfrid Ganander (1741–1790) on merkinnyt sananloppuista k:ta sanakirjaansa ja Mythologia Fennicaan kirjaamiinsa kansanrunoteksteihin, jotka on julkaistu Suomen kansan vanhat runot -teoksen XV osassa. Tutkimukseni sivuaa folkloristiikkaa, mutta sijoittuu pääosin vanhan kirjasuomen tutkimuksen piiriin. Filologisessa analyysissani vertaan Gananderin runotekstejä muihin kansanrunoteksteihin ja selvittelen niiden suhteita sekä tekstien alkuperää ja historiaa. Tulkitsen runotekstien äänne- ja muotorakennetta kontekstin avulla sekä tekstin kulttuurihistorialliselta pohjalta. Tulokseni osoittavat, että Ganander merkitsi -k:ta selvästi enemmän kuin muut aikalaisensa. Aiemmassa tutkimuksessa Gananderin loppu-k:n merkintää on moitittu epäjohdonmukaiseksi. Loppu-k:n esiintyminen aineistossani ei olekaan morfologisesti säännöllistä sillä tavalla, että esimerkiksi imperatiiveissa olisi aina systemaattisesti k. Säännönmukaisuus näkyy kuitenkin siinä, että loppu-k:lliset tapaukset sijoittuvat aika hyvin yleisiin käsityksiin loppu-k:n esiintymisestä. Aineistossani on silti muutamia erikoisia ja myös virheellisinä pidettäviä loppu-k-tapauksia. Epäsäännöllistä merkintätapaa selittää se, että Gananderilla on ollut hallussaan samasta runosta useita erilaisia tekstejä. Gananderin loppu-k:n merkintään näkyvät vaikuttaneen lähinnä runosäkeiden lähdetekstit ja paikallisuus, morfologia, äänneympäristö ja säetyyppi. Ganander näyttää silti operoineen jonkin verran tietoisestikin loppu-k:lla. Osoituksena tästä ovat paitsi hänen itse tuottamissaan teksteissä esiintyvät muutamat loppu-k:t myös eräät filologisen analyysini tulokset. Oleellista on, että Ganander on merkinnyt -k:n historiallisesti odotuksenmukaiseen paikkaan. Hänellä näyttää siis olleen jonkinlainen käsitys siitä, mihin loppu-k kuuluu. Ganander näyttää olleen varsin uskollinen lähteidensä loppu-k:n merkinnälle. Erityisen kiinnostavaa on kuitenkin se, että hän on merkinnyt loppu-k:ta myös sellaisiin säkeisiin, joiden lähdetekstissä -k:ta ei ole merkitty. Gananderilla on voinut olla hallussaan näistä runoista sellaisia vanhoja muistiinpanoja, joita muilla ei ole ollut tai joita muiden kokoelmissa ei ole säilynyt. Nämä säkeet saattaisivat jopa edustaa Gananderin itsensä keräämää runoaineistoa. Ganander näyttäisi tavoittaneen ja panneen muistiin sellaista harvinaista ja vanhaa kielellistä ainesta, jota ei ole muualla juuri säilynyt. Filologina Ganander oli monimuotoinen, kriittinen ja valistunut, mutta hän kehitti joitakin analyysejaan pelkästään runosäkeiden perusteella. Hänen sanakirjassaan on myös virheellisiä ja sekavia tulkintoja. Gananderin kansanrunoteksteihin pohjautuvat sanakirjasitaatit saattavat tuntua mielikuvituksellisilta siksikin, että hän selittää niissä kansanrunojen maailmaa. Gananderin filologinen tulkinta on jättänyt jälkensä myöhempiin teoksiin – kaikkine virheineenkin. Näin runokieli Gananderin kirjaamana on päässyt vaikuttamaan suomen kielen kuvaukseen sanakirjoissa ja kieliopeissa. Kansanrunojen kielen tutkimus ja analyysi voivat siis osaltaan valaista suomen kielen tieteellisen kuvauksen historiaa

Deontic autonomy in family interaction:directive actions and the multimodal organization of going to the bathroom

Abstract The multimodal conversation analysis in this paper shows how an au pair and a mother use several turns consisting of various bodily and multilingual elements to persuade a 5-year-old to go to the bathroom. We examine the participants’ orientation to the child’s deontic autonomy; that is, his right to determine his own actions. The analysis shows that although the au pair and child disagree on whether the child should go to the bathroom, they both orient to the same norms of interaction and the norm of deontic autonomy more specifically

Testing end-to-end self-management in a wireless future internet environment

Federated testbeds aim at interconnecting experimental facilities to provide a larger-scale, more diverse and higher performance platform for accomplishing tests and experiments for future Internet new paradigms. In this work the Panlab experimental facilities and specifically the Octopus network testbed has been used in order to experiment on the improvement of QoS features by using the Self-NET software for self-management over a WiMAX network environment. The monitoring and configuration capabilities that different administrative domains provide has been exploited in order to test network and service layers cooperation for more efficient end-to-end self-management. The performance results from the experiments that have been performed prove that the proposed self-management solution and the mechanisms for the selection of the appropriate network or service level adaptation improve end-to-end behaviour and QoS features. © 2011 Springer-Verlag Berlin Heidelberg

Yhdeksäsluokkalaisten näkemyksiä yläkoululaisten luku- ja kirjoitustaidoista

Tiivistelmä Tarkastelemme yhdeksäsluokkalaisten näkemyksiä yläkoululaisten luku- ja kirjoitustaidoista. Tutkimuskysymyksemme ovat seuraavat: mitä ja miten yhdeksäsluokkalaiset puhuvat yläkoululaisten luku- ja kirjoitustaidoista. Aineistonamme on 75 kyselylomakevastausta, joita tarkastelemme argumentaatioanalyysin ja suhtautumisen teorian keinoin. Lomakkeen ensimmäisen kysymyksen virikkeenä oli pääkirjoitus, jossa tuotiin esiin huoli nuorten luku- ja kirjoitustaitojen heikkenemisestä. Vastaajia pyydettiin ottamaan kantaa pohjatekstiin ja perustelemaan mielipiteensä. Suurin osa vastaajista jakoi pohjatekstissä esitetyn huolen taitojen heikkenemisestä, mutta vastauksissa nousi esiin myös kritiikki koko ikäryhmää ja poikia koskevia yleistyksiä kohtaan. Toisessa kysymyksessä vastaajia pyydettiin kertomaan oma mielipiteensä yläkoululaisten luku- ja kirjoitustaidoista. Yhdeksäsluokkalaiset arvioivat yläkoululaisten luku- ja kirjoitustaitoja pääsääntöisesti myönteisesti.Abstract Ninth grade pupils’ views on the reading and writing skills of middle schoolers We examine the views of 9th grade pupils on the reading and writing skills of middle schoolers. Our research questions are the following: what do 9th grade pupils talk about when discussing the reading and writing skills of upper comprehensive school pupils and how do they talk about it? Our data consists of 75 questionnaire responses, which we examine using argumentation analysis and appraisal theory. The first question of the questionnaire used an editorial discussing the concern over declining reading and writing skills of the youth as a stimulus for the pupils’ response. The participants were asked to discuss the editorial and give reasons for their opinions. Most respondents shared the concern over the decline of these skills but the respondents also criticised the generalisations regarding the whole age group and boys in particular. In the second question, the respondents were asked to give their own opinion about the reading and writing skills of upper comprehensive school pupils. Overall, pupils evaluated the reading and writing skills of upper comprehensive school pupils positively

Towards a usage-based model of early code-switching:evidence from three language pairs

Abstract Usage-based studies trace children’s early language back to slot-and-frame patterns which dominate spontaneous language use. We apply the Traceback method to data from three bilingual children with English as one of their languages and Polish, German, or Finnish as the other to examine what these children’s code-switching has in common and how it differs in light of the genealogical distance between the languages used. Their bilingual constructions are derived from individual corpora of naturalistic interactions of each child respectively and traced back to monolingual language produced previously to establish whether they are unprocessed chunks or partially schematic units. Based on this, we propose a model of switching which helps us to distinguish between the qualitative aspects of bilingual use in these two types of combinations. Our results show that all three children filter out some mixing occurring in chunks before these give basis to longer units. Whatever bilingual combinations remain frozen in those units can be explained by phonological overlap of the children’s two languages, which is highest in the acquisition of English-German due to their genealogical proximity