Study of miRNA polymorphisms and their potential association with breast cancer risk in Australian Caucasian populations

This project established a large and well characterised prospective breast cancer DNA biobank and used this biobank to conduct genetic studies in breast cancer. The thesis presented the results of these high-throughput genotyping studies in two separate Australian Caucasian case-control populations and identified association between three novel genetic variants in microRNA genes and breast cancer risk.

Submission to House of Representatives Standing Committee on Economics Inquiry into Home Ownership

This paper empirically examines the effect of current tax policy on home ownership, specifically looking at how developer contributions impact house prices. Developer contributions are a commonly used mechanism for local governments to pay for new urban infrastructure. This research applies a hedonic house price model to 4,699 new and 25,053 existing house sales in Brisbane from 2005 to 2011. The findings of is research are consistent with international studies that support the proposition that developer contributions are over passed. This study has provided evidence that suggest developer contributions are over passed to both new and existing homes in the order of around 400%. These findings suggest that developer contributions are thus a significant contributor to increasing house prices, reduced housing supply and are thus an inefficient and inequitable tax. By testing this effect on both new and existing homes, this research provides evidence in support of the proposition that not only are developer contributions over passed to new home buyers but also to buyers of existing homes. Thus the price inflationary effect of these developer contributions are being felt by all home buyers across the community, resulting in increased mortgage repayments of close to $1,000 per month in Australia. This is the first study to empirically examine the impact of developer contributions on house prices in Australia. These results are important as they inform governments on the outcomes of current tax policy on home ownership, providing the first evidence of its kind in Australia. This is an important contribution to the tax reform agenda in Australia.

Association between biomechanical structural stresses of atherosclerotic carotid plaques and subsequent ischaemic cerebrovascular events - A longitudinal in vivo magnetic resonance imaging-based finite element study

Background: High-resolution magnetic resonance (MR) imaging has been used for MR imaging-based structural stress analysis of atherosclerotic plaques. The biomechanical stress profile of stable plaques has been observed to differ from that of unstable plaques; however, the role that structural stresses play in determining plaque vulnerability remains speculative. Methods: A total of 61 patients with previous history of symptomatic carotid artery disease underwent carotid plaque MR imaging. Plaque components of the index artery such as fibrous tissue, lipid content and plaque haemorrhage (PH) were delineated and used for finite element analysis-based maximum structural stress (M-C Stress) quantification. These patients were followed up for 2 years. The clinical end point was occurrence of an ischaemic cerebrovascular event. The association of the time to the clinical end point with plaque morphology and M-C Stress was analysed. Results: During a median follow-up duration of 514 days, 20% of patients (n=12) experienced an ischaemic event in the territory of the index carotid artery. Cox regression analysis indicated that M-C Stress (hazard ratio (HR): 12.98 (95% confidence interval (CI): 1.32-26.67, pZ0.02), fibrous cap (FC) disruption (HR: 7.39 (95% CI: 1.61e33.82), p Z 0.009) and PH (HR: 5.85 (95% CI: 1.27e26.77), p Z 0.02) are associated with the development of subsequent cerebrovascular events. Plaques associated with future events had higher M-C Stress than those which had remained asymptomatic (median (interquartile range, IQR): 330 kPa (229e494) vs. 254 kPa (166-290), p Z0.04). Conclusions: High biomechanical structural stresses, in addition to FC rupture and PH, are associated with subsequent cerebrovascular events.

Association between aneurysm shoulder stress and abdominal aortic aneurysm expansion: A longitudinal follow-up study

Background Aneurysm expansion rate is an important indicator of the potential risk of abdominal aortic aneurysm (AAA) rupture. Stress within the AAA wall is also thought to be a trigger for its rupture. However, the association between aneurysm wall stresses and expansion of AAA is unclear. Methods and Results Forty-four patients with AAAs were included in this longitudinal follow-up study. They were assessed by serial abdominal ultrasonography and computed tomography scans if a critical size was reached or a rapid expansion occurred. Patient-specific 3-dimensional AAA geometries were reconstructed from the follow-up computed tomography images. Structural analysis was performed to calculate the wall stresses of the AAA models at both baseline and final visit. A nonlinear large-strain finite element method was used to compute the wall-stress distribution. The relationship between wall stresses and expansion rate was investigated. Slowly and rapidly expanding aneurysms had comparable baseline maximum diameters (median, 4.35 cm [interquartile range, 4.12 to 5.0 cm] versus 4.6 cm [interquartile range, 4.2 to 5.0 cm]; P=0.32). Rapidly expanding AAAs had significantly higher shoulder stresses than slowly expanding AAAs (median, 300 kPa [interquartile range, 280 to 320 kPa] versus 225 kPa [interquartile range, 211 to 249 kPa]; P=0.0001). A good correlation between shoulder stress at baseline and expansion rate was found (r=0.71; P=0.0001). Conclusion A higher shoulder stress was found to have an association with a rapidly expanding AAA. Therefore, it may be useful for estimating the expansion of AAAs and improve risk stratification of patients with AAAs.

Association of NOS1AP variants and depression phenotypes in schizophrenia

Background The nitric oxide synthase 1 adaptor protein gene (NOS1AP) has previously been recognised as a schizophrenia susceptibility gene due to its role in glutamate neurotransmission. The gene is believed to inhibit nitric oxide (NO) production activated by the N-methyl-d-aspartate (NMDA) receptor and reduced NO levels have been observed in schizophrenia patients. However, association studies investigating NOS1AP and schizophrenia have produced inconsistent results, most likely because schizophrenia is a clinically heterogeneous disorder. This study aims to investigate the association between NOS1AP variants and defined depression phenotypes of schizophrenia. Methods Nine NOS1AP SNPs, rs1415259, rs1415263, rs1858232, rs386231, rs4531275, rs4656355, rs4657178, rs6683968 and rs6704393 were genotyped in 235 schizophrenia subjects screened for various phenotypes of depression. Result One NOS1AP SNP (rs1858232) was associated with the broad diagnosis of schizophrenia and eight SNPs were associated with depression related phenotypes within schizophrenia. The rs1415259 SNP showed strong association with sleep dysregulation phenotypes of depression. Conclusion Results suggest that NOS1AP variants are associated with various forms of depression in schizophrenia and are more prevalent in males. Limitation Schizophrenia is a clinically heterogeneous disease that can vary greatly between different ethnic and geographic populations so our observations should be viewed with caution until they are independently replicated, particularly in larger patient cohorts.

Scottish Football Association or Sweet Fanny Adams

Tämä pro gradu -tutkielma käsittelee kielisidonnaisen huumorin kääntämistä. Ennen itse kääntämisen käsittelyä täytyy kuitenkin määritellä mitä tarkoitetaan käsitteellä kielisidonnainen huumori . Aluksi käsitellään huumoria ja sen ominaisuuksia sekä huumorin ja kulttuuristen, fysiologisten ja sosiaalisten tekijöiden suhdetta. Huumori syntyy kun tietyt odotukset rikotaan, eli toimitaan joidenkin normien vastaisesti. Huumorin eräitä perusperiaatteita ovat ristiriitaisuus ja yhteensopimattomuus. Kielisidonnaisessa huumorissa ristiriitaisuus ja yhteensopimattomuus on havaittavissa kielen tasolla: kieltä käytetään tuottamaan moniselitteinen tai -mielinen koominen ilmaus. Sanaleikki, jossa käytetään yhtä sanaa jolla on yksi tai useampi merkitys, on tyypillinen esimerkki kielisidonnaisesta huumorista. Mutta kielisidonnainen huumori ei rajoitu pelkästään tämänkaltaisiin sanaleikkeihin (engl. pun), vaan kattaa käsitteenä laajemman valikoiman erilaisia kielisidonnaisen huumorin muotoja, esimerkiksi monimerkityksiset nimet, idiomaattisilla ilmauksilla tuotettu huumori, akrostikonit, kirjoituksen konventioita rikkomalla tuotettu huumori jne. Kielisidonnainen huumori on tutkielmassa luokiteltu ja määritelty omaksi huumorin alalajikseen. Kielisidonnaisen huumorin kielellinen monimerkityksisyys tekee sen kääntämisestä vaikeampaa kuin sellaisen tekstin, jossa kielen tasolla ei ilmene monimerkityksisyyttä. Tästä syystä kielisidonnainen huumori tarvitsee erilaisen käännösstrategian kuin esimerkiksi tieteellinen teksti. Seuraavaksi käydään aluksi läpi joitakin käännösteorian keskeisiä käsitteitä ja niiden suhdetta ja vaikutuksia kielisidonnaisen huumorin kääntämiseen. Sitten kuvataan kielisidonnaisen huumorin käännösprosessi, joka jakautuu kolmeen osaan: tunnistaminen, analyysi ja kääntäminen. Näiden kolmen pohjalta laaditaan kuuden eri käännösstrategian ryhmä. Kuusi eri päästrategiaa ovat käännössidonnaisen huumorikategorian säilyttäminen, kirjaimellinen käännös, muun tyylikeinon käyttäminen, kompensaatio, poisjättö ja toimitukselliset keinot. Strategiat käydään läpi deskriptiivisesti ja niiden käyttöä valaistaan esimerkkien avulla. Osa päästrategioista jakautuu alastrategioihin, jotka kuvaavat tarkemmin, minkälaisin keinoin lähtökielen kielisidonnainen käännösongelma voidaan siirtää kohdekieleen. Strategiat pyritään kuvaamaan siten, että ne voisivat olla avuksi käännettäessä minkä tahansa kieliparin välillä. Vaikka kuvatut käännösstrategiat käydään läpi deskriptiivisesti, on pyrkii tutkielma myös olemaan avuksi käytännön tilanteissa kielisidonnaista huumoria käännettäessä. Tätä varten on tutkielman lopussa annettu kuvaus yhden kielisidonnaisen huumoriongelman kääntämisprosessista. Yhdistämällä teoria käytäntöön kuvataan käännösprosessiesimerkissä yhden kielisidonnaisen huumoriongelman analyysi-ja kääntämisvaiheet. Tuloksena on viisi erilaista versiota samasta lähtötekstin käännösongelmasta. Tutkielma siis ensinnäkin määrittelee, mitä ja minkälaista on kielisidonnainen huumori sekä luokittelee sen. Toisekseen tutkielma kuvaa sen käännösprosessin ja määrittelee eri käännösstrategiat. Lisäksi esimerkin avulla esitellään eri käännösvaihtoehtoja. Avainsanat: kääntäminen, huumori, sanaleikki, kielisidonnainen

On global summer monsoonal drought mechanics

It is shown that within the framework of a linear five-level quasi-geostrophic steady state global model the middle latitude systems can always have significant influence on the Asian summer monsoonal system through the lower tropospheric monsoonal westerly window region around 80°E. It is hypothesized that quasistationarity of the middle latitude longwave systems results in stronger teleconnections through this window and the consequent monsoon breaks when the phase is right.

Association of microRNA 17–92 cluster host gene (MIR17HG) polymorphisms with breast cancer

Breast cancer incidence and mortality rates are increasing despite our current knowledge on the disease. Ninety-five percent of breast cancer cases correspond to sporadic forms of the disease and are believed to involve an interaction between environmental and genetic determinants. The microRNA 17–92 cluster host gene (MIR17HG) has been shown to regulate expression of genes involved in breast cancer development and progression. Study of single-nucleotide polymorphisms (SNPs) located in this cluster gene could help provide a further understanding of its role in breast cancer. Therefore, this study investigated six SNPs in the MIR17HG using two independent Australian Caucasian case–control populations (GRC-BC and GU-CCQ BB populations) to determine association to breast cancer susceptibility. Genotyping was undertaken using chip-based matrix assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry (MS). We found significant association between rs4824505 and breast cancer at the allelic level in both study cohorts (GRC-BC p = 0.01 and GU-CCQ BB p = 0.03). Furthermore, haplotypic analysis of results from our combined population determined a significant association between rs4824505/rs7336610 and breast cancer susceptibility (p = 5 × 10−4). Our study is the first to show that the A allele of rs4824505 and the AC haplotype of rs4824505/rs7336610 are associated with risk of breast cancer development. However, definitive validation of this finding requires larger cohorts or populations in different ethnical backgrounds. Finally, functional studies of these SNPs could provide a deeper understanding of the role that MIR17HG plays in the pathophysiology of breast cancer.

Sisustaminen on kuin käsialaa : Carin Bryggman ja Lasse Ollinkari sisustusarkkitehdin ammatissa 1940- ja 1950-luvulla

"Interior Design is Like Handwriting." Carin Bryggman and Lasse Ollinkari as Interior Designers in the 1940s and 1950s My dissertation deals with the emergence of the interior designer's profession in Finland with focus on the 1940s and 1950s, the postwar years of reconstruction and modernism, as the historical context. The topic is addressed at both the collective and individual levels. Specific subjects of study are the training of interior designers (also known as interior architects), the association of Finnish interior architects (Sisustusarkkitehdit SIO), the professional field and its public image and two leading designers, Carin Bryggman (1920 1993) and Lasse Ollinkari (1921 1993). Though respected figures within the field, Bryggman and Ollinkari have otherwise remained little known and studied. My study presents a great deal of new empiria. The main materials consist of the documents of related institutions and the archives of Bryggman and Ollinkari, in which drawings and photographs figure prominently. The drawings illustrate in a new way the variety of professional tasks in the field. My results are also based on a large body of interviewed material. The materials are approached from two theoretical perspectives, with gender and margins as core concepts from the perspective of women's studies. The even gender division of Finnish interior designers revealed a difference with regard to neighbouring occupations and other countries. I claim that the division of tasks was not defined by gender. The second theoretical basis is the sociological study of professions. The high professional status achieved by interior designers is shown by the fact that of the many related titles in Finnish and Swedish, such as "furniture draughtsman" or "interior artist", interior architect became the established one, despite opposition from architects. My hypothesis that the professionalization of interior designers took place during the two postwar decades proved to be correct. The profession emerged through specialized education and became established with the founding of its own professional organization. From the outset, the goal was to mark a distinction between professionals of interior and furniture design and other designers and architects. Interior designers became a strong and successful modern professional group, involved in a wide range of projects from objects to interiors. Keywords: interior designers, interior architects, interior art, occupations, gender, professions, interior design, furniture, home, public space, Carin Bryggman, Lasse Ollinkari, the Sisustusarkkitehdit SIO association, 1940s and 1950s, reconstruction, modernism.

Evaluation of Inoculated Lablab Silage for Growing Dairy Heifers

A summer grown forage legume crop – Lablab (Lablab purpureus) harvested in autumn, was ensiled as plastic wrapped, large round bales. Of the 30 bales produced, 13 were inoculated with a bacterial inoculant containing Lactobacillus plantarum and Enterococcus faecium. Inoculant was premixed at 30 g/litre water, cultured overnight (18 hours) then sprayed onto cut forage during the baling and wrapping procedure at 1 litre per tonne of silage. A replicated feeding experiment was conducted in July - August 1998 (5 weeks), using 24 eight month old Holstein Friesian heifers group fed non-inoculated or inoculated silage to appetite plus 2 kg rolled sorghum grain/heifer.day. Chemical composition and nutritive value of well preserved bales of control and inoculated silages were similar (P>0.05) with 50% DM and 26 g N and 6.8 MJ ME per kg DM. Lactic acid and acetic acid concentrations were 11.4 v. 11.4 and 4.90 v. 3.75 g/kg DM for control and inoculated silages respectively (P>0.05). Heifers preferentially selected leaf from the silage offered and maintained liveweight gains of 0.70 and 0.61 kg/day respectively (P>0.05) during the silage feeding period. High DM and low WSC content of the parent forage may have reduced the opportunity for the bacterial inoculant to have effect. Animal production for a consuming world : proceedings of 9th Congress of the Asian-Australasian Association of Animal Production Societies [AAAP] and 23rd Biennial Conference of the Australian Society of Animal Production [ASAP] and 17th Annual Symposium of the University of Sydney, Dairy Research Foundation, [DRF]. 2-7 July 2000, Sydney, Australia.

Response By Dairy Cows Grazing Tropical Grass Pasture To Barley or Sorghum Grain Based Concentrates and Lucerne Hay

This study investigated the responses by dairy cows grazing Callide Rhodes grass (Chloris gayana cv. Callide) pasture to supplementation with barley or sorghum based concentrates (5 grain:1 cotton seed meal) or barley concentrate plus lucerne (Medicago sativa) hay. It was conducted in summer - autumn 1999 with 20 spring calved cows in 4 treatments in 3 consecutive periods of 4 weeks. Rain grown pastures, heavily stocked at 4.4 cows/ha, provided 22 to 35 kg green DM and 14 to 16 kg green leaf DM/cow.day in periods 1 to 3. Supplements were fed individually twice daily after milking. Cows received 6 kg concentrate/day in period 1, increased by 1 kg/day as barley, sorghum or lucerne chaff in each of periods 2 and 3. The Control treatment received 6 kg barley concentrate in all 3 periods. Milk yields by cows fed sorghum were lower than for cows fed equivalent levels of barley-based concentrate (P<0.05). Faecal starch levels (14, 18 and 17%) for cows fed sorghum concentrate were much higher (P<0.01) than those of cows fed similar levels of barley (2.1, 1.2 and 1.7%) in each period respectively. Additional supplementation as lucerne chaff did not increase milk production (P>0.05). Increased concentrate supplementation did not alleviate the problem of low protein in milk produced by freshly calved Holstein-Friesian cows grazing tropical grass pasture in summer. Animal production for a consuming world : proceedings of 9th Congress of the Asian-Australasian Association of Animal Production Societies [AAAP] and 23rd Biennial Conference of the Australian Society of Animal Production [ASAP] and 17th Annual Symposium of the University of Sydney, Dairy Research Foundation, [DRF]. 2-7 July 2000, Sydney, Australia.

Impact of African orography and the Indian summer monsoon on the low-level Somali jet

The low-level jet (LLJ) over the Indian region, which is most prominent during the monsoon (June-September) season, has been studied with a general circulation model (GCM). The role of African orography in modulating this jet is the focus of this article. The presence o African orography intensifies the cross-equatorial flow. Contrary to previous modelling Studies we find that cross-equatorial flow occurs even in the absence of African orography, though this flow is muc weaker even when the Indian monsoon rainfall is high. However, the location of the meridional jet near the equator in the Somali region is linked to the Indian monsoon rainfall rather than to the land-sea contrast over Somalia. Also, the presence of African orography, and not the strength of the Indian monsoon, controls the vertical extent of the equatorial meridional wind. In an aqua-planet simulation, the cross-equatorial flow occurs about 30 to the west of the rainfall maximum. Thus, the longitudinal location of the equatorial Somali jet depends upon the occurrence of monsoon heating, but the vertical structure of the jet is on account of the western boundary current in the atmosphere due to the East African highlands under the influence of monsoonal heat source.

Genetic association analysis of miRNA SNPs implicates MIR145 in breast cancer susceptibility

Background MicroRNAs (miRNAs) are important small non-coding RNA molecules that regulate gene expression in cellular processes related to the pathogenesis of cancer. Genetic variation in miRNA genes could impact their synthesis and cellular effects and single nucleotide polymorphisms (SNPs) are one example of genetic variants studied in relation to breast cancer. Studies aimed at identifying miRNA SNPs (miR-SNPs) associated with breast malignancies could lead towards further understanding of the disease and to develop clinical applications for early diagnosis and treatment. Methods We genotyped a panel of 24 miR-SNPs using multiplex PCR and chip-based matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) analysis in two Caucasian breast cancer case control populations (Primary population: 173 cases and 187 controls and secondary population: 679 cases and 301 controls). Association to breast cancer susceptibility was determined using chi-square (X 2 ) and odds ratio (OR) analysis. Results Statistical analysis showed six miR-SNPs to be non-polymorphic and twelve of our selected miR-SNPs to have no association with breast cancer risk. However, we were able to show association between rs353291 (located in MIR145) and the risk of developing breast cancer in two independent case control cohorts (p = 0.041 and p = 0.023). Conclusions Our study is the first to report an association between a miR-SNP in MIR145 and breast cancer risk in individuals of Caucasian background. This finding requires further validation through genotyping of larger cohorts or in individuals of different ethnicities to determine the potential significance of this finding as well as studies aimed to determine functional significance. Keywords: Association analysis; Breast cancer; microRNA; miR-SNPs; MIR145

Inverse Correlation between Vitamin D and C-Reactive Protein in Newborns

Some studies suggested that adequate vitamin D might reduce inflammation in adults. However, little is known about this association in early life. We aimed to determine the relationship between cord blood 25-hydroxyvitamin D (25(OH)D) and C-reactive protein (CRP) in neonates. Cord blood levels of 25(OH)D and CRP were measured in 1491 neonates in Hefei, China. Potential confounders including maternal sociodemographic characteristics, perinatal health status, lifestyle, and birth outcomes were prospectively collected. The average values of cord blood 25(OH)D and CRP were 39.43 nmol/L (SD = 20.35) and 6.71 mg/L (SD = 3.07), respectively. Stratified by 25(OH)D levels, per 10 nmol/L increase in 25(OH)D, CRP decreased by 1.42 mg/L (95% CI: 0.90, 1.95) among neonates with 25(OH)D <25.0 nmol/L, and decreased by 0.49 mg/L (95% CI: 0.17, 0.80) among neonates with 25(OH)D between 25.0 nmol/L and 49.9 nmol/L, after adjusting for potential confounders. However, no significant association between 25(OH)D and CRP was observed among neonates with 25(OH)D ≥50 nmol/L. Cord blood 25(OH)D and CRP levels showed a significant seasonal trend with lower 25(OH)D and higher CRP during winter-spring than summer-autumn. Stratified by season, a significant linear association of 25(OH)D with CRP was observed in neonates born in winter-spring (adjusted β = −0.11, 95% CI: −0.13, −0.10), but not summer-autumn. Among neonates born in winter-spring, neonates with 25(OH)D <25 nmol/L had higher risk of CRP ≥10 mg/L (adjusted OR = 3.06, 95% CI: 2.00, 4.69), compared to neonates with 25(OH)D ≥25 nmol/L. Neonates with vitamin D deficiency had higher risk of exposure to elevated inflammation at birth.