804 resultados para Vet


Relevância:

10.00% 10.00%

Publicador:

Resumo:

Because of its size, its excellent VET history, and its emerging higher education provision, AIM is in a special position to be an exemplar of good practice in the VET-HE transition. Many dual sector providers, by virtue of their size, tend to focus on higher education, on the assumption that VET ‘competence’ implies that their VET entrants to HE are confident and capable in information literacy skills. While this is only one of the many challenges that such students face in their undergraduate programs, it is the most critical for most of them in their quest for academic success. All students (school leavers, gap-year participants, articulating, mature age) entering HE will face specific challenges. For articulating students, the nature of credit transfer arrangements will often mean they commence studies in units that are not designated first year units. In this case, the embedded support structures are not as prominent. The existing literature is not consistent in reports on the rates of completion, retention and attrition of articulating students. There is some evidence that VET-qualified students have higher retention rates than school leavers [1], but limited information literacy skills can lead to attrition [2].

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Tutkimuksen tavoitteena on hahmottaa 1800-luvulla tapahtunutta keskiluokan sosiaalista nousua pohjalaissyntyisen papin, opettajan, liikemiehen ja valtiopäiväedustajan Alfred Kihlmanin (1825-1904) elämänvaiheiden kautta. Kyseessä ei ole perinteinen elämäkerta, vaan työn pyrkimyksenä on mikrotason tarkan analyysin kautta päästä käsiksi laajempiin yhteiskunnallisiin muutosprosesseihin. Erityisen kiinnostuksen kohteena ovat erilaiset sosiaaliset verkostot sekä niiden merkitys Kihlmanin kaltaisen keskiluokkaisen yksilön sosiaaliselle nousulle. Tutkimus jakautuu kahteen pääosaan, joista ensimmäinen käsittelee heränneiden pappien verkostoja 1840-luvulla ja 1850-luvun alussa ja jälkimmäinen liikemiesverkostoja 1850-luvun jälkipuolelta 1870-luvun alkuun. Pääasiallisena lähdeaineistona on Alfred Kihlmanin laaja kirjeenvaihto. Alfred Kihlman liittyi kouluvuosinaan 1840-luvun alussa nuorison piirissä nopeasti levinneeseen herännäisyyteen. Nuoret heränneet papit muodostivat tiiviin sosiaalisen verkoston, joka perustui jaetulle uskonnolliselle ideologialle sekä pappisperheiden välisille avioliittositeille. Lisäksi verkostoa pidettiin yllä yhteisillä kokoontumisilla, vierailuilla, kirjeenvaihdolla sekä palvelusten vaihtamisella. Verkoston välityksellä saatiin tehokkaasti mm. informaatiota sekä rahalainoja. Herännäisyys nousi nuoren keskiluokkaisen papiston omaa yhteiskunnallista voimattomuuttaan kohtaan tuntemasta tyytymättömyydestä. Kun sivistyneistön mahdollisuudet menestyä perinteisillä foorumeilla olivat autonomian alkupuolella heikot, nuoret heränneet kielsivät uskonnollisessa ideologiassaan arvon maalliselta menestykseltä ja rakensivat oman verkostonsa, jonka sisällä he saattoivat toteuttaa pätemisentarvettaan. Yhteiskunnallisen tilanteen muututtua verkosto muuttui 1850-luvun alussa hyödystä rasitteeksi, minkä seurauksena heränneiden pappien rivit hajaantuivat. Irtauduttuaan herännäisyydestä Alfred Kihlman siirtyi opettajan uralle. Heränneeltä vaimoltaan perimänsä varallisuuden sekä nuoruus- ja herännäisvuosinaan solmimiensa ystävyyssuhteiden ansiosta hän ajatui 1850-luvun kuluessa yhä enemmän myös liike-elämään. Hänen merkittävimmäksi toimintakentäkseen muodostuivat Suomen Yhdyspankki sekä Tampereen Pellava- ja Rautateollisuus, jonka johtajana hän toimi vuodesta 1866 lähtien. 1860-luvulla liikemiesverkostot perustuivat suurelta osin sukulaisuuteen, mutta yhä enenevässä määrin myös ystävyys-, kollega- ja liikekumppanuussuhteisiin. Kun pankkilaitos oli vielä hyvin kehittymätön, verkostot olivat etenkin pääomien hankinnassa avainasemassa. Tiiviit lainaverkostot olivat huonojen suhdanteiden aikana toisaalta myös vaaraksi, sillä yksi suuri konkurssi saattoi vetää mukanaan joukoittain liikemiehiä. Verkostojen kautta voitiin välittää ja saada myös suosituksia sekä sisäpiiritietoa, jota ei ollut saatavissa muista lähteistä. Yhteiskunnan muuttuminen ja henkilösuhteet mahdollistivat Alfred Kihlmanin sosiaalisen nousun. Teollistuminen ja liike-elämän vapautuminen tarjosivat uusia mahdollisuuksia keskiluokan yritteliäille yksilöille. Ylempien yhteiskuntaluokkien välisten säätyjen välisten raja-aitojen tasaantuminen tekivät 1850-luvun puolivälissä mahdolliseksi myös papin osallistumisen liike-elämään. Avainsanat: sosiaaliset verkostot - Suomi - 1800-luku - herännäisyys - kirkkohistoria - taloushistoria

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Det har knappast undgått någon som är språkligt medveten att finlandssvenskan och sverigesvenskan skiljer sig åt till vissa delar. Olikheterna återfinns på olika språkliga nivåer. Mest kända och omskrivna är de lexikologiska skillnaderna, dvs. skillnaderna på ordplanet. Betydligt mindre uppmärksamhet har ägnats syntaktiska skillnader, dvs. skillnader i hur satser och meningar byggs upp. För att öka kunskapen om finlandssvensk syntax initierade Språkvetenskapliga nämnden vid Svenska litteratursällskapet i Finland projektet Svenskan i Finland – syntaktiska drag i ett jämförande perspektiv, som pågick åren 2004–2006. Min avhandling har kommit till inom ramen för det projektet. Prepositionerna (t.ex. av, i, på, för, till, åt osv.) är så kallade funktionsord som har till uppgift att binda samman de mer betydelsetunga orden till satser och meningar. Den finlandssvenska prepositionsanvändningen skiljer sig i viss mån från den sverigesvenska, och ”åt” är en av de prepositioner som ofta lyfts fram som exempel. Finlandssvenskarna säger t.ex. ”han gav en bok åt Lena” i stället för ”han gav en bok till Lena” eller ”han gav Lena en bok”. De säger ”berätta något åt någon” (i stället för ”för”) och de säger ”ringa åt någon” i stället för ”ringa någon”. Ett huvudsyfte med min undersökning är att ta reda på hur pass stora skillnaderna är om man ser till samtliga belägg på ”åt” i ett material och inte bara till sådana som man fäster sig vid för att man vet att de avviker i finlandssvenskan. Undersökningen är korpusbaserad. Det betyder att jag letat efter alla belägg på kombinationer av verb och prepositionen ”åt” i rätt stora textmassor som finns tillgängliga i elektronisk form. Materialet ligger i Språkbanken i Finland och omfattar huvudsakligen tidningstext och skönlitteratur. Jag har använt mig av en textmassa på sammanlagt ungefär 40 miljoner löpande ord, drygt 23 miljoner finlandssvenska och drygt 19 miljoner sverigesvenska. Det materialet gav ca 20 000 åt-belägg att studera, och det visade sig något oväntat att ”åt” inte alls är vanligare i finlandssvenskan än i sverigesvenskan när det gäller skriftspråk, åtminstone inte i professionella skribenters språk. Om man kompenserar för att den finlandssvenska och den sverigesvenska korpusen inte är helt lika i fråga om genrefördelning och ålder, kommer man fram till i stort sett samma frekvens för ”åt” i båda korpusarna. För den närmare analysen av vilka mönster åt-beläggen uppvisar har jag först och främst utnyttjat konstruktionsgrammatik men också ramsemantik och valensteori. Konstruktionsgrammatiken är ingen enhetlig teori, men tanken om grammatiska konstruktioner är gemensam. Konstruktioner representerar allt från generella syntaktiska mönster till specifika mönster för språkliga enskildheter. Uppfattningen om vad som ska inbegripas i begreppet varierar, men definitionen av ”konstruktion” som ”par (eller konstellationer) av form och betydelse” är gemensam. ”Konstruktion” avser aldrig konkreta belägg i texter eller yttranden utan alltid det abstrakta mönstret bakom dessa. Och varje yttrande är resultatet av att en stor mängd konstruktioner samverkar. I min analys har jag utgått ifrån att beläggen med ”åt” kan återföras på olika konstruktioner eller mönster utifrån vad som är gemensamt för grupper av belägg. Jag har sett på vad åt-frasen i samverkan med verbet har för funktion i beläggen. En åt-fras är syntaktiskt en prepositionsfras och består av en preposition och en rektion. Exempelvis utgör ordparet ”åt skogen” en prepositionsfras där ”skogen” är rektion. Ur mitt material har jag kunnat abstrahera fram fem övergripande mönster där referenten för rektionen har olika så kallade semantiska roller. Åt-frasen kan i kombination med verbet ange mål eller riktmärke, som i t.ex. svänga åt höger, dra åt helvete, ta sig åt hjärtat, luta åt en seger för IFK. Den kan för det andra ange mottagare (t.ex. ge varsin kaka åt hundarna, bygga en bastu åt sina svärföräldrar, skaffa biljetter åt en kompis). För det tredje kan åt-frasen avse en referent som har nytta (eller skada) av en aktion (t.ex. klippa häcken åt grannen, ställa in digitalboxen åt sin moster). Åt-frasen kan slutligen avse den eller det som är föremål antingen för en kommunikationsaktion (vinka åt sin son, skratta åt eländet) eller en attityd eller känsla (glädja sig åt framgången). Utöver dessa huvudmönster finns det ett antal smärre grupper av belägg som bildar egna mönster, men de utgör sammanlagt under 3 % i bägge korpusarna. Inom grupperna kan undermönster urskiljas. I t.ex. mottagargruppen representerar ”ge varsin kaka åt hundarna” överföringskonstruktion, ”bygga en bastu åt sina svärföräldrar” produktionskonstruktion och ”skaffa biljetter åt en kompis” ombesörjningskonstruktion. Alla typer är gemensamma för bägge materialen, men andelen belägg som representerar de olika typerna skiljer sig betydligt. I det sverigesvenska materialet står t.ex. det mönster där åt-frasen avser mål eller riktmärke för en mycket större andel av beläggen än i finlandssvenskan. Också andelen belägg där åt-frasen avser någon som har nytta (eller skada) av en aktion är mycket högre i det sverigesvenska materialet. I det finlandssvenska materialet står i gengäld mottagarbeläggen för över 50 % av beläggen medan andelen i det sverigesvenska materialet är bara 30 %. Inom gruppen utgör belägg av produktions- och ombesörjningstyp dessutom en mindre andel i det finlandssvenska materialet än i det sverigesvenska. Dessa står till sin funktion nära den typ som avser den som har nytta av aktionen. De konkreta beläggen på överföring (ge varsin kaka åt hundarna) utgör en större andel i det finlandssvenska materialet än i det sverigesvenska (ca 8 % mot 3 %), men typiskt för båda materialen är hög kollokationsgrad (”kollokation” avser par eller grupper av ord som uppträder oftare tillsammans än de statiskt sett skulle göra vid helt slumpmässig förekomst). Största delen av mottagarbeläggen utgörs av fraser av typen ”ge arbete åt någon, ge eftertryck åt något, ge liv åt något; ägna tid åt något, ägna sitt liv åt något, ägna uppmärksamhet åt något”. De här slutsatserna gäller alltså skriftspråk. I talspråk ser fördelningen annorlunda ut. Typiskt för prepositionen ”åt” är överhuvudtaget hög kollokationsgrad. Det förefaller som om språkanvändarna har tydliga, färdiga mallar för var ”åt” kan komma in. Det enda mönster som verkar helt produktivt, i den meningen att elementen är i stort sett fritt kombinerbara, är kombinationer av verb och åt-fras där åt-frasen avser den som har nytta av något. Att någon utför något för någons räkning verkar överlag kunna uttryckas med prepositionen ”åt”: t.ex. ”tvätta bilen åt pappa, ringa efter en taxi åt kunden”. Till och med belägg av typen ”hon drömde åt honom att bli ordinarie adjunkt” förekommer i någon mån. Konstruktionen är produktiv i båda språkvarieteterna men uppenbart är att konstruktion med mottagare har tolkningsföreträde i vissa fall i finlandssvenskan: ”Filip skrev ett brev åt sin syster” tolkas av sverigesvenskar som att Filip skrev brevet för systerns räkning, medan finlandssvenskar överlag uppenbarligen tolkar det som att Filip skrev till sin syster, att systern var mottagare av brevet. Ungefär 20 % av alla belägg i båda materialen representerar fall där ”åt” utgör partikel. Verb och ”åt” är närmare förbundna med varandra än när ”åt” utgör normal preposition. Exempel på partikelbelägg är ”han kom inte åt strömbrytaren, det gick åt mängder med saft, landet får dra åt svångremmen, de roffade åt sig de bästa platserna”. Också partikelmaterialet ser på ett generellt plan väldigt lika ut i båda språkvarieteterna. Den största skillnaden uppvisar den reflexiva typen ”roffa åt sig”. Medan typen är mycket homogen i det sverigesvenska materialet är variationen större i det finlandsvenska. Dels uppträder fler verb i kombinationen (han köpte åt sig ett par jeans), dels vacklar ordföljden (han nappade åt sig ett paraply ~ han nappade ett paraply åt sig). Att ”åt” används mer i vissa funktioner i finlandsvenskan brukar förklaras med påverkan från finskans allativ (ändelsen -lle: hän antoi kirjan Astalle > hon gav en bok åt Asta). Allt tyder dock på att den finlandssvenska åt-användningen delvis är en relikt. I äldre sverigesvenska källor träffar man på ”åt” i sådana kontexter som numera är typiska för finlandsvenskan. Det finlandssvenska språkområdet ligger ute i periferin i relation till det språkliga centrum som förändringar sprider sig från (för svenskans del främst Stockholmstrakten) och typiskt för perifera områden är att de uppvisar ålderdomliga drag också när inga kontaktfenomen spelar in. Allativen kan naturligtvis ha bidragit till att bevara användningen av ”åt” i finlandssvenskan. Att det är just ”åt” som används” beror antagligen på att prepositionen har flest funktioner gemensamt med allativen rent kognitivt om man jämför med de betydligt mer frekventa prepositionerna ”till” och ”för”. Uppenbart är också att åt-användningen därtill lever sitt eget liv i finlandssvenskan. I vissa varieteter av finlandssvenska kan man t.ex. höra yttranden av typ ”alla fiskarna dog åt dom”. Som språklig enskildhet har det ingen finsk förebild med allativ. Yttrandet är ett exempel på töjning av en svensk konstruktion. Modell finns dels i det mönster där åt avser den som har nytta eller skada av något, dels i relationell användning av ”åt”: han är hantlangare åt Eriksson ~ han är Erikssons hantlangare. Vid språkkontakt är det överlag konstruktioner som har förebild i det låntagande språket som lånas in från det långivande språket, medan konstruktioner som saknar förebild är betydligt mindre benägna att vinna insteg.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

A restriction analysis of PCR (PCR-REA) amplified apxIVA gene has been suggested as an alternative method for serotyping of Actinobacillus pleuropneumoniae by Jaglic et al. [Jaglic, Z., Svastova, P., Rychlik, I., Nedbalcova, K., Kucerova, Z., Pavlik, I., Bartos, M., 2004. Differentiation of Actinobacillus pleuropneumoniae by PCR-REA based on sequence variability of the apxIVA gene and by ribotyping. Vet. Microbiol. 103, 63-69]. The current study investigated whether this alternative method could distinguish between the reference strains of serovars 13-15 and the value of the method when applied to 47 field isolates representing serovars 1-3, 5, 7-9, 12 and 15 as well as non-typable isolates. The reference strains of serovars 13 and 14 had the same sized product after the apxIVA PCR, while the product for serovar 15 was of different size compared to all the other serovar reference strains. The CfoI digest profiles of the reference serovars 13 and 14 strains were different from each other and from all other serovars. The HpaII digest profiles of these two serovars were very similar to each other, but both were distinctively different from the other serovar profiles. The CfoI digest profile of serovar 15 strain was very similar to the serovars 3 and 12 strains except for two faint extra bands for serovar 15. The HpaII digest profiles of serovars 12 and 15 reference strains were identical. The PCR-REA method correctly recognized the serovar of 21 of 43 field isolates. It was concluded that the method was a useful additional tool to support, but could not replace, conventional serotyping.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

A Campylobacter fetus subsp. venerealis-specific 5' Taq nuclease PCR assay using a 3' minor groove binder-DNA probe (TaqMan MGB) was developed based on a subspecies-specific fragment of unknown identity (S. Hum, K. Quinn, J. Brunner, and S. L. On, Aust. Vet. J. 75:827-831, 1997). The assay specifically detected four C. fetus subsp. venerealis strains with no observed cross-reaction with C. fetus subsp. fetus-related Campylobacter species or other bovine venereal microflora. The 5' Taq nuclease assay detected approximately one single cell compared to 100 and 10 cells in the conventional PCR assay and 2,500 and 25,000 cells from selective culture from inoculated smegma and mucus, respectively. The respective detection limits following the enrichments from smegma and mucus were 5,000 and 50 cells/inoculum for the conventional PCR compared to 500 and 50 cells/inoculum for the 5' Taq nuclease assay. Field sampling confirmed the sensitivity and the specificity of the 5' Taq nuclease assay by detecting an additional 40 bulls that were not detected by culture. Urine-inoculated samples demonstrated comparable detection of C. fetus subsp. venerealis by both culture and the 5' Taq nuclease assay; however, urine was found to be less effective than smegma for bull sampling. Three infected bulls were tested repetitively to compare sampling tools, and the bull rasper proved to be the most suitable, as evidenced by the improved ease of specimen collection and the consistent detection of higher levels of C. fetus subsp. venerealis. The 5' Taq nuclease assay demonstrates a statistically significant association with culture (2 = 29.8; P < 0.001) and significant improvements for the detection of C. fetus subsp. venerealis-infected animals from crude clinical extracts following prolonged transport.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Role models incite admiration and provide inspiration, contributing to learning as students aspire to emulate their example. The attributes of physician role models for medical trainees are well documented, but they remain largely unexplored in the context of veterinary medical training. The aim of the current study was to describe the attributes that final-year veterinary students (N=213) at the University of Queensland identified when reflecting on their clinical role models. Clinical role model descriptions provided by students were analyzed using concept-mapping software (Leximancer v. 2.25). The most frequent and highly connected concepts used by students when describing their role model(s) included clients, vet, and animal. Role models were described as good communicators who were skilled at managing relationships with clients, patients, and staff. They had exemplary knowledge, skills, and abilities, and they were methodical and conducted well-structured consultations. They were well respected and, in turn, demonstrated respect for clients, colleagues, staff, and students alike. They were also good teachers and able to tailor explanations to suit both clients and students. Findings from this study may serve to assist with faculty development and as a basis for further research in this area.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Understanding the process of cell division is crucial for modern cancer medicine due to the central role of uncontrolled cell division in this disease. Cancer involves unrestrained proliferation as a result of cells loosing normal control and being driven through the cell cycle, where they normally would be non-dividing or quiescent. Progression through the cell cycle is thought to be dependent on the sequential activation of cyclin-dependent kinases (Cdks). The full activation of Cdks requires the phosphorylation of a conserved residue (threonine-160 on human Cdk2) on the T-loop of the kinase domain. In metazoan species, a trimeric complex consisting of Cdk7, cyclin H and Mat1 has been suggested to be the T-loop kinase of several Cdks. In addition, Cdk7 have also been implicated in the regulation of transcription. Cdk7, cyclin H, and Mat1 can be found as subunits of general transcription factor TFIIH. Cdk7, in this context, phosphorylates the Carboxy-terminal domain (CTD) of the large subunit of RNA polymerase II (RNA pol II), specifically on serine-5 residues of the CTD repeat. The regulation of Cdk7 in these and other functions is not well known and the unambiguous characterization of the in vivo role of Cdk7 in both T-loop activation and CTD serine-5 phosphorylation has proved challenging. In this study, the fission yeast Cdk7-cyclin H homologous complex, Mcs6-Mcs2, is identified as the in vivo T-loop kinase of Cdk1(Cdc2). It also identifies multiple levels of regulation of Mcs6 kinase activity, i.e. association with Pmh1, a novel fission yeast protein that is the apparent homolog of metazoan Mat1, and T-loop phosphorylation of Mcs6, mediated by Csk1, a monomeric T-loop kinase with similarity to Cak1 of budding yeast. In addition, Skp1, a component of the SCF (Skp1-Cullin-F box protein) ubiquitin ligase is identified by its interactions with Mcs2 and Pmh1. The Skp1 association with Mcs2 and Pmh1 is however SCF independent and does not involve proteolytic degradation but may reflect a novel mechanism to modulate the activity or complex assembly of Mcs6. In addition to Cdk7, also Cdk8 has been shown to have CTD serine-5 kinase activity in vitro. Cdk8 is not essential in yeast but has been shown to function as a transcriptional regulator. The function of Cdk8 is unknown in flies and mammals. This prompted the investigation of murine Cdk8 and its potential role as a redundant CTD serine-5 kinase. We find that Cdk8 is required for development prior to implantation, at a time that is co-incident with a burst of Cdk8 expression during normal development. The results does not support a role of Cdk8 as a serine-5 CTD kinase in vivo but rather shows an unexpected requirement for Cdk8, early in mammalian development. The results presented in this thesis extends our current knowledge of the regulation of the cell cycle by characterizing the function of two distinct cell cycle regulating T-loop kinases, including the unambiguous identification of Mcs6, the fission yeast Cdk7 homolog, as the T-loop kinase of Cdk1. The results also indicate that the function of Mcs6 is conserved from fission yeast to human Cdk7 and suggests novel mechanisms by which the distinct functions of Cdk7 and Mcs6 could be regulated. These findings are important for our understanding of how progression of the cell cycle and proper transcription is controlled, during normal development and tissue homeostasis but also under condition where cells have escaped these control mechanisms e.g. cancer.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The recently proposed $338 million merger of Australian vet and pet products companies Greencross and Petbarn illustrates something that perhaps we have known for a while now: our pets are becoming more important to us than ever before. Pets are no longer viewed simply as animals, but have become “humanised” to the point that they are considered by many to be members of the family. Indeed, nearly 90% of Australians polled in a recent survey said they thought of their dog or cat as a member of the family, and even admitted to treating them better than human family members, which has a substantial impact on purchasing behaviours...

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Various endogenous and exogenous factors have been reported to increase the risk of breast cancer. Many of those are related to prolonged lifetime exposure to estrogens. Furthermore, a positive family history of breast cancer and certain benign breast diseases are known to increase the risk of breast cancer. The role of lifestyle factors, such as use of alcohol and smoking has been an area of intensive study. Alcohol has been found to increase the risk of breast cancer, whereas the role of smoking has remained obscure. A multitude of enzymes are involved in the metabolism of estrogens and xenobiotics including the carcinogens found in tobacco smoke. Many of the metabolic enzymes exhibit genetic polymorphisms that can lead to inter-individual differences in their abilities to modify hazardous substrates. Therefore, in presence of a given chemical exposure, one subgroup of women may be more susceptible to breast carcinogenesis, since they carry unfavourable forms of the polymorphic genes involved in the metabolism of the chemical. In this work, polymorphic genes encoding for cytochrome P450 (CYP) 1A1 and 1B1, N-acetyl transferase 2 (NAT2), sulfotransferase 1A1 (SULT1A1), manganese superoxide dismutase (MnSOD) and vitamin D receptor (VDR) were investigated in relation to breast cancer susceptibility in a Finnish population. CYP1A1, CYP1B1 and SULT1A1 are involved in the metabolism of both estrogens and xenobiotics, whereas NAT2 is involved only in the latter. MnSOD is an antioxidant enzyme protecting cells from oxidative damage. VDR, in turn, mediates the effects of the active form of vitamin D (1,25(OH)2D3, calcitriol) on maintenance of calcium homeostasis and it has anti-proliferative effects in many cancer cells. A 1.3-fold (95% CIs 1.01-1.73) increased risk of breast cancer was seen among women who carried the NAT2 slow acetylator genotype and a 1.5-fold (95% CI 1.1-2.0) risk was found in women with a MnSOD variant A allele containing genotypes compared to women with the NAT2 rapid acetylator genotype or to those with the MnSOD VV genotype, respectively. Instead, women with the VDR a allele containing genotypes were found to be at a decreased risk for breast cancer (OR 0.73; 95% CI 0.54-0.98) compared to women with the AA genotype. No significant overall associations were found between SULT1A1 or CYP genotypes and breast cancer risk, whereas a combination of the CYP1B1 432Val allele containing genotypes with the NAT2 slow acetylator genotypes posed a 1.5-fold (95% CI 1.03-2.24) increased risk. Moreover, NAT2 slow acetylator genotype was found to be confined to women with an advanced stage of breast cancer (stages III and IV). Further evidence for the association of xenobiotic metabolising genes with breast cancer risk was found when active smoking was taken into account. Women who smoked less than 10 cigarettes/day and carried at least one CYP1B1 432Val variant allele, were at 3.1-fold (95% CI 1.32-7.12) risk of breast cancer compared to women who smoked the same amount but did not carry the variant allele. Furthermore, the risk was significantly increased with increasing number of the CYP1B1 432Val alleles (p for trend 0.005). In addition, women who smoked less than 5 pack-years and carried the NAT2 slow acetylator genotype were at a 2.6-fold (95% CI 1.01-6.48) increased risk of breast cancer compared to women who smoked the same amount but carried the NAT2 rapid acetylator genotype. Furthermore, the combination of the CYP1B1 432Val allele and the NAT2 slow acetylator genotype increased the risk of breast cancer by 2.5-fold (95% CI 1.11-5.45) among ever smokers. Instead, the MnSOD A allele was found to be a risk factor among postmenopausal long-term smokers (>15 years of smoking) (OR 5.1; 95% CI 1.4-18.4) or among postmenopausal women who had smoked more than 10 cigarettes/day (OR 5.5; 95% CI 1.3-23.4) compared to women who had similar smoking habits but carried the MnSOD V/V genotype. Similarly, within subgroups of postmenopausal women who were using oral contraceptives, hormone replacement therapy or alcohol, women carrying the MnSOD A allele genotypes seemed to be at increased risk of breast cancer compared to women with the MnSOD V/V genotype. A positive family history of breast cancer and high parity were shown to be inversely associated with breast cancer risk among women carrying the VDR ApaI a allele or among premenopausal women carrying the SULT1A1*2 allele, respectively.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The actin cytoskeleton is essential for a large variety of cell biological processes. Actin exists in either a monomeric or a filamentous form, and it is very important for many cellular functions that the local balance between these two actin populations is properly regulated. A large number of proteins participate in the regulation of actin dynamics in the cell, and twinfilin, one of the proteins examined in this thesis, belongs to this category. The second level of regulation involves proteins that crosslink or bundle actin filaments, thereby providing the cell with a certain shape. α-Actinin, the second protein studied, mainly acts as an actin crosslinking protein. Both proteins are conserved in organisms ranging from yeast to mammals. In this thesis, the roles of twinfilin and α-actinin in development were examined using Drosophila melanogaster as a model organism. Twinfilin is an actin monomer binding protein that is structurally related to cofilin. In vitro, twinfilin reduces actin polymerisation by sequestering actin monomers. The Drosophila twinfilin (twf) gene was identified and found to encode a protein functionally similar to yeast and mammalian twinfilins. A strong hypomorphic twf mutation was identified, and flies homozygous for this allele were viable and fertile. The adult twf mutant flies displayed reduced viability, a rough eye phenotype and severely malformed bristles. The shape of the adult bristle is determined by the actin bundles that are regularly spaced around the perimeter of the developing pupal bristles. Examination of the twf pupal bristles revealed an increased level of filamentous actin, which in turn resulted in splitting and displacement of the actin bundles. The bristle defect was rescued by twf overexpression in developing bristles. The Twinfilin protein was localised at sites of actin filament assembly, where it was required to limit actin polymerisation. A genetic interaction between twinfilin and twinstar (the gene encoding Cofilin) was detected, consistent with the model predicting that both proteins act to limit the amount of filamentous actin. α-Actinin has been implicated in several diverse cell biological processes. In Drosophila, the only function for α-actinin yet known is in the organisation of the muscle sarcomere. Muscle and non-muscle cells utilise different α-actinin isoforms, which in Drosophila are produced by alternative splicing of a single gene. In this work, novel α-actinin deletion alleles, including ActnΔ233, were generated, which specifically disrupted the transcript encoding the non-muscle α-actinin isoform. Nevertheless, ActnΔ233 homozygous mutant flies were viable and fertile with no obvious defects. By comparing α-actinin protein distribution in wild type and ActnΔ233 mutant animals, it could be concluded that non-muscle α-actinin is the only isoform expressed in young embryos, in the embryonic central nervous system and in various actin-rich structures of the ovarian germline cells. In the ActnΔ233 mutant, α-actinin was detected not only in muscle tissue, but also in embryonic epidermal cells and in certain follicle cell populations in the ovaries. The population of α-actinin protein present in non-muscle cells of the ActnΔ233 mutant is referred to as FC-α-actinin (Follicle Cell). The follicular epithelium in the Drosophila ovary is a well characterised model system for studies on patterning and morphogenesis. Therefore, α-actinin expression, regulation and function in this tissue were further analysed. Examination of the α-actinin localisation pattern revealed that the basal actin fibres of the main body follicle cells underwent an organised remodelling during the final stages of oogenesis. This involved the assembly of a transient adhesion site in the posterior of the cell, in which α-actinin and Enabled (Ena) accumulated. Follicle cells genetically manipulated to lack all α-actinin isoforms failed to remodel their cytoskeleton and translocate Ena to the posterior of the cell, while the actin fibres as such were not affected. Neither was epithelial morphogenesis disrupted. The reorganisation of the basal actin cytoskeleton was also disturbed following ectopic expression of Decapentaplegic (Dpp) or as a result of a heat shock. At late oogenesis, the main body follicle cells express both non-muscle α-actinin and FC-α-actinin, while the dorsal anterior follicle cells express only non-muscle α-actinin. The dorsal anterior cells are patterned by the Dpp and Epidermal growth factor receptor (EGFR) signalling pathways, and they will ultimately secrete the dorsal appendages of the egg. Experiments involving ectopic activation of EGFR and Dpp signalling showed that FC-α-actinin is negatively regulated by combined EGFR and Dpp signalling. Ubiquitous overexpression of the adult muscle-specific α-actinin isoform induced the formation of aberrant actin bundles in migrating follicle cells that did not normally express FC-α-actinin, provided that the EGFR signalling pathway was activated in the cells. Taken together, this work contributes new data to our knowledge of α-actinin function and regulation in Drosophila. The cytoskeletal remodelling shown to depend on α-actinin function provides the first evidence that α-actinin has a role in the organisation of the cytoskeleton in a non-muscle tissue. Furthermore, the cytoskeletal remodelling constitutes a previously undescribed morphogenetic event, which may provide us with a model system for in vivo studies on adhesion dynamics in Drosophila.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The continuous production of blood cells, a process termed hematopoiesis, is sustained throughout the lifetime of an individual by a relatively small population of cells known as hematopoietic stem cells (HSCs). HSCs are unique cells characterized by their ability to self-renew and give rise to all types of mature blood cells. Given their high proliferative potential, HSCs need to be tightly regulated on the cellular and molecular levels or could otherwise turn malignant. On the other hand, the tight regulatory control of HSC function also translates into difficulties in culturing and expanding HSCs in vitro. In fact, it is currently not possible to maintain or expand HSCs ex vivo without rapid loss of self-renewal. Increased knowledge of the unique features of important HSC niches and of key transcriptional regulatory programs that govern HSC behavior is thus needed. Additional insight in the mechanisms of stem cell formation could enable us to recapitulate the processes of HSC formation and self-renewal/expansion ex vivo with the ultimate goal of creating an unlimited supply of HSCs from e.g. human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPS) to be used in therapy. We thus asked: How are hematopoietic stem cells formed and in what cellular niches does this happen (Papers I, II)? What are the molecular mechanisms that govern hematopoietic stem cell development and differentiation (Papers III, IV)? Importantly, we could show that placenta is a major fetal hematopoietic niche that harbors a large number of HSCs during midgestation (Paper I)(Gekas et al., 2005). In order to address whether the HSCs found in placenta were formed there we utilized the Runx1-LacZ knock-in and Ncx1 knockout mouse models (Paper II). Importantly, we could show that HSCs emerge de novo in the placental vasculature in the absence of circulation (Rhodes et al., 2008). Furthermore, we could identify defined microenvironmental niches within the placenta with distinct roles in hematopoiesis: the large vessels of the chorioallantoic mesenchyme serve as sites of HSC generation whereas the placental labyrinth is a niche supporting HSC expansion (Rhodes et al., 2008). Overall, these studies illustrate the importance of distinct milieus in the emergence and subsequent maturation of HSCs. To ensure proper function of HSCs several regulatory mechanisms are in place. The microenvironment in which HSCs reside provides soluble factors and cell-cell interactions. In the cell-nucleus, these cell-extrinsic cues are interpreted in the context of cell-intrinsic developmental programs which are governed by transcription factors. An essential transcription factor for initiation of hematopoiesis is Scl/Tal1 (stem cell leukemia gene/T-cell acute leukemia gene 1). Loss of Scl results in early embryonic death and total lack of all blood cells, yet deactivation of Scl in the adult does not affect HSC function (Mikkola et al., 2003b. In order to define the temporal window of Scl requirement during fetal hematopoietic development, we deactivated Scl in all hematopoietic lineages shortly after hematopoietic specification in the embryo . Interestingly, maturation, expansion and function of fetal HSCs was unaffected, and, as in the adult, red blood cell and platelet differentiation was impaired (Paper III)(Schlaeger et al., 2005). These findings highlight that, once specified, the hematopoietic fate is stable even in the absence of Scl and is maintained through mechanisms that are distinct from those required for the initial fate choice. As the critical downstream targets of Scl remain unknown, we sought to identify and characterize target genes of Scl (Paper IV). We could identify transcription factor Mef2C (myocyte enhancer factor 2 C) as a novel direct target gene of Scl specifically in the megakaryocyte lineage which largely explains the megakaryocyte defect observed in Scl deficient mice. In addition, we observed an Scl-independent requirement of Mef2C in the B-cell compartment, as loss of Mef2C leads to accelerated B-cell aging (Gekas et al. Submitted). Taken together, these studies identify key extracellular microenvironments and intracellular transcriptional regulators that dictate different stages of HSC development, from emergence to lineage choice to aging.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Teaching with digital technologies is essential to the development of 21st century students’ graduate capabilities. However, relatively little is known about the extent to which Queensland VET teachers engage with digitally-enhanced teaching, or have the capacity to do so. Using a mixed methods approach, this thesis investigated the current digital teaching capacities of VET teachers and how current professional development opportunities are helping to address their learning needs.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

This study analyses personal relationships linking research to sociological theory on the questions of the social bond and on the self as social. From the viewpoint of disruptive life events and experiences, such as loss, divorce and illness, it aims at understanding how selves are bound to their significant others as those specific people ‘close or otherwise important’ to them. Who form the configurations of significant others? How do different bonds respond in disruptions and how do relational processes unfold? How is the embeddedness of selves manifested in the processes of bonding, on the one hand, and in the relational formation of the self, on the other? The bonds are analyzed from an anti-categorical viewpoint based on personal citations of significance as opposed to given relationship categories, such as ‘family’ or ‘friendship’ – the two kinds of relationships that in fact are most frequently significant. The study draws from analysis of the personal narratives of 37 Finnish women and men (in all 80 interviews) and their entire configurations of those specific people who they cite as ‘close or otherwise important’. The analysis stresses the subjective experiences, while also investigating the actualized relational processes and configurations of all personal relationships with certain relationship histories embedded in micro-level structures. The research is based on four empirical sub-studies of personal relationships and a summary discussing the questions of the self and social bond. Discussion draws from G. H. Mead, C. Cooley, N. Elias, T. Scheff, G. Simmel and the contributors of ‘relational sociology’. Sub-studies analyse bonds to others from the viewpoint of biographical disruption and re-configuration of significant others, estranged family bonds, peer support and the formation of the most intimate relationships into exclusive and inclusive configurations. All analyses examine the dialectics of the social and the personal, asking how different structuring mechanisms and personal experiences and negotiations together contribute to the unfolding of the bonds. The summary elaborates personal relationships as social bonds embedded in wider webs of interdependent people and social settings that are laden with cultural expectations. Regarding the question of the relational self, the study proposes both bonding and individuality as significant. They are seen as interdependent phases of the relationality of the self. Bonding anchors the self to its significant relationships, in which individuality is manifested, for example, in contrasting and differentiating dynamics, but also in active attempts to connect with others. Individuality is not a fixed quality of the self, but a fluid and interdependent phase of the relational self. More specifically, it appears in three formats in the flux of relational processes: as a sense of unique self (via cultivation of subjective experiences), as agency and as (a search for) relative autonomy. The study includes an epilogue addressing the ambivalence between the social expectation of individuality in society and the bonded reality of selves.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

This thesis explores migration and the attractiveness of urban living in the Greater Helsinki region. The aim of the thesis is to explore the attractiveness of the city of Helsinki in terms of regional migration and to identify what characterizes migration to Helsinki. The study focuses in particular on housing, which is a key factor influencing migration decisions in the region. Other central themes in the study are housing policy and regional competition among municipalities. This study focuses solely on households moving within Finnish borders excluding international migration. Migration is examined by comparing in- and out-migration in Helsinki, as well as studying migration to the city s inner and outer areas. The primary research material in the study is a questionnaire data collected by the National Consumer Research Centre. In this thesis the data is used for studying migrants aged 25 45. The main research method is analyzing the data statistically using the SPSS software. Methods include frequency analysis, cross tabulation, factor analysis and descriptive analysis. Additionally, statistical data is used to complement the questionnaire data. The research results indicate that Helsinki s in- and out-migration differs both in terms of the type of households that migrate as well as in the reasons why they migrate. Furthermore, differences can also be detected between migration to the inner and outer parts of Helsinki. According to the research results, a household s current phase of life is crucial in determining where and why they move within the Greater Helsinki region. A household s set of values on the other hand, seems to have a lesser impact on migration within the region, even though households moving to Helsinki seem to value a somewhat more urban lifestyle than the ones moving out of the city. The research also shows a direct correlation between the values of migrants and their current phase of life. Decisions of migrating are heavily influenced by wider societal issues. In the Greater Helsinki region the labor and housing market appear to have a great influence on the direction of migration streams. According to the results, households move to and from Helsinki for different reasons. The primary reasons for moving to Helsinki are related to the city s diverse labor market and to the working careers of households. Issues related to urban living and an urban lifestyle seem to be relevant although not the main reason why people move to Helsinki. The research material indicates that Helsinki s urban environment is both a pull and a push factor affecting the decisions of migrants. The city attracts those seeking urban living, but on the contrary does not appeal to households seeking more space and wishing to live closer to nature. According to the research, Helsinki with its densely built urban environment mainly attracts singles and childless couples, whereas the city region s other municipalities are more attractive for families with children. Housing policy is one of the main reasons determining where people move within the Helsinki region. As for the city of Helsinki, improving the city s attractiveness seems to be closely linked to how well the city manages to execute its future housing policies and how well alternative living preferences can be taken into account in planning.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Major advances in the treatment of preterm infants have occurred during the last three decades. Survival rates have increased, and the first generations of preterm infants born at very low birth weight (VLBW; less than 1500 g) who profited from modern neonatal intensive care are now in young adulthood. The literature shows that VLBW children achieve on average lower scores on cognitive tests, even after exclusion of individuals with obvious neurosensory deficits. Evidence also exists for an increased risk in VLBW children for various neuropsychiatric disorders such as attention-deficit hyperactivity disorder (ADHD) and related behavioral symptoms. Up till now, studies extending into adulthood are sparse, and it remains to be seen whether these problems persist into adulthood. The aim of this thesis was to study ADHD-related symptoms and cognitive and executive functioning in young adults born at VLBW. In addition, we aimed to study sleep disturbances, known to adversely affect both cognition and attention. We hypothesized that preterm birth at VLBW interferes with early brain development in a way that alters the neuropsychological phenotype; this may manifest itself as ADHD symptoms and impaired cognitive abilities in young adulthood. In this cohort study from a geographically defined region, we studied 166 VLBW adults and 172 term-born controls born from 1978 through 1985. At ages 18 to 27 years, the study participants took part in a clinic study during which their physical and psychological health was assessed in detail. Three years later, 213 of these individuals participated in a follow-up. The current study is part of a larger research project (The Helsinki Study of Very Low Birth Weight Adults), and the measurements of interest for this particular study include the following: 1) The Adult Problem Questionnaire (APQ), a self-rating scale of ADHD-related symptoms in adults; 2) A computerized cognitive test battery designed for population studies (CogState®) which measures core cognitive abilities such as reaction time, working memory, and visual learning; 3) Sleep assessment by actigraphy, the Basic Nordic Sleep Questionnaire, and the Morningness-Eveningness Questionnaire. Actigraphs are wrist-worn accelerometers that separate sleep from wakefulness by registering body movements. Contrary to expectations, VLBW adults as a group reported no more ADHD-related behavioral symptoms than did controls. Further subdivision of the VLBW group into SGA (small for gestational age) and AGA (appropriate for gestational age) subgroups, however, revealed more symptoms on ADHD subscales pertaining to executive dysfunction and emotional instability among those born SGA. Thus, it seems that intrauterine growth retardation (for which SGA served as a proxy) is a more essential predictor for self-perceived ADHD symptoms in adulthood than is VLBW birth as such. In line with observations from other cohorts, the VLBW adults reported less risk-taking behavior in terms of substance use (alcohol, smoking, and recreational drugs), a finding reassuring for the VLBW individuals and their families. On the cognitive test, VLBW adults free from neurosensory deficits had longer reaction times than did term-born peers on all tasks included in the test battery, and lower accuracy on the learning task, with no discernible effect of SGA status over and above the effect of VLBW. Altogether, on a group level, even high-functioning VLBW adults show subtle deficits in psychomotor processing speed, visual working memory, and learning abilities. The sleep studies provided no evidence for differences in sleep quality or duration between the two groups. The VLBW adults were, however, at more than two-fold higher risk for sleep-disordered breathing (in terms of chronic snoring). Given the link between sleep-disordered breathing and health sequelae, these results suggest that VLBW individuals may benefit from an increased awareness among clinicians of this potential problem area. An unexpected finding from the sleep studies was the suggestion of an advanced sleep phase: The VLBW adults went to bed earlier according to the actigraphy registrations and also reported earlier wake-up times on the questionnaire. In further study of this issue in conjunction with the follow-up three years later, the VLBW group reported higher levels of morningness propensity, further corroborating the preliminary findings of an advanced sleep phase. Although the clinical implications are not entirely clear, the issue may be worth further study, since circadian rhythms are closely related to health and well-being. In sum, we believe that increased understanding of long-term outcomes after VLBW, and identification of areas and subgroups that are particularly vulnerable, will allow earlier recognition of potential problems and ultimately lead to improved prevention strategies.