Something rotten in the state of Minnesota: or the morality of backwoodsmen: 'A Simple Plan'

'A Simple Plan' is a deceptively complex and multilayered film, combining elements of Celtic mythology with the morality play and the windfall fantasy gone disastrously wrong. Despite its blending of realism and heavyhanded symbolism, and its abundant trans-textual gestures, 'A Simple Plan' is in many ways defiantly not a 90s movie: its leading characters are fashionably flawed, but they are neither sensitive, nor honourable, nor heroic; there are no startling special effects or intricate timeshifts; and it desperately gives the impression of depth, of being emphatically more than mere superficial excess. At a stretch it almost appears to be a throwback to the 1930s Production Code emphasis on the role of cinema in moral instruction; while good hardly triumphs over evil, venality is painfully and emphatically punished. But in other ways it is a quintessential late 90s film: an American/British/Japanese/German/French co-production, 'A Simple Plan' acts most palpably as a commentary on the moral, economic and social condition of the United States at the end of the American century.

Association of immunoproteasomes with the endoplasmic reticulum

Proteasomes are complex multisubunit proteases which play a critical role in intracellular proteolysis. Immunoproteasomes, which contain three c-interferon-inducible subunits, are a subset of proteasomes which have a specialized function in antigen processing for presentation by the MHC class I pathway. Two of the c-interferon inducible subunits, LMP2 and LMP7, are encoded within the MHC class II region adjacent to the two TAP (transporter associated with antigen presentation) genes. We have investigated the localization of immunoproteasomes using monoclonal antibodies to LMP2 and LMP7. Immunoproteasomes were strongly enriched around the endoplasmic reticulum as judged by double-immuno¯uorescence experiments with anticalreticulin antibodies, but were also present in the nucleus and throughout the cytosol. In contrast, proteasome subunit C2, which is present in all proteasomes, was found to be evenly distributed throughout the cytoplasm and in the nucleus, as was the delta subunit, which is replaced by LMP2 in immunoproteasomes. c-Interferon increased the level of immunoproteasomes, but had no effect on their distribution. Our results provide the ®rst direct evidence that immunoproteasomes are strongly enriched at the endoplasmic reticulum, where they may be located close to the TAP transporter to provide efficient transport of peptides into the lumen of the endoplasmic recticulum for association with MHC class I molecules.

User participation in the categorisation of the State Library of Queensland digital image collections: characteristics, motivations and experiences

In 2010, the State Library of Queensland (SLQ) donated their out-of-copyright Queensland images to Wikimedia Commons. One direct effect of publishing the collections at Wikimedia Commons is the ability of general audiences to participate and help the library in processing the images in the collection. This paper will discuss a project that explored user participation in the categorisation of the State Library of Queensland digital image collections. The outcomes of this project can be used to gain a better understanding of user participation that lead to improving access to library digital collections. Two techniques for data collection were used: documents analysis and interview. Document analysis was performed on the Wikimedia Commons monthly reports. Meanwhile, interview was used as the main data collection technique in this research. The data collected from document analysis was used to help the researchers to devise appropriate questions for interviews. The interviews were undertaken with participants who were divided into two groups: SLQ staff members and Wikimedians (users who participate in Wikimedia). The two sets of data collected from participants were analysed independently and compared. This method was useful for the researchers to understand the differences between the experiences of categorisation from both the librarians’ and the users’ perspectives. This paper will provide a discussion on the preliminary findings that have emerged from each group participant. This research provides preliminary information about the extent of user participation in the categorisation of SLQ collections in Wikimedia Commons that can be used by SLQ and other interested libraries in describing their digital content by their categorisations to improve user access to the collection in the future.

The state-of-the-art in personalized recommender systems for social networking

With the explosion of Web 2.0 application such as blogs, social and professional networks, and various other types of social media, the rich online information and various new sources of knowledge flood users and hence pose a great challenge in terms of information overload. It is critical to use intelligent agent software systems to assist users in finding the right information from an abundance of Web data. Recommender systems can help users deal with information overload problem efficiently by suggesting items (e.g., information and products) that match users’ personal interests. The recommender technology has been successfully employed in many applications such as recommending films, music, books, etc. The purpose of this report is to give an overview of existing technologies for building personalized recommender systems in social networking environment, to propose a research direction for addressing user profiling and cold start problems by exploiting user-generated content newly available in Web 2.0.

Genetic association of the KLK4 locus with risk of prostate cancer

The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs) in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (±10 kb) in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥7) revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the Ptrend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r2≥0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.

Factors influencing funding decisions by elected politicians at the state/provincial level : a case study of public libraries in Canada

The purpose of this study was to determine factors (internal and external) that influenced Canadian provincial (state) politicians when making funding decisions about public libraries. Using the case study methodology, Canadian provincial/state level funding for public libraries in the 2009-10 fiscal year was examined. After reviewing funding levels across the country, three jurisdictions were chosen for the case: British Columbia's budget revealed dramatically decreased funding, Alberta's budget showed dramatically increased funding, and Ontario's budget was unchanged from the previous year. The primary source of data for the case was a series of semi-structured interviews with elected officials and senior bureaucrats from the three jurisdictions. An examination of primary and secondary documents was also undertaken to help set the political and economic context as well as to provide triangulation for the case interviews. The data were analysed to determine whether Cialdini's theory of influence (2001) and specifically any of the six tactics of influence (i.e, commitment and consistency, authority, liking, social proof, scarcity and reciprocity) were instrumental in these budget processes. Findings show the principles of "authority", "consistency and commitment" and "liking" were relevant, and that "liking" were especially important to these decisions. When these decision makers were considering funding for public libraries, they most often used three distinct lenses: the consistency lens (what are my values? what would my party do?), the authority lens (is someone with hierarchical power telling me to do this? are the requests legitimate?), and most importantly, the liking lens (how much do I like and know about the requester?). These findings are consistent with Cialdini's theory, which suggests the quality of some relationships is one of six factors that can most influence a decision maker. The small number of prior research studies exploring the reasons for increases or decreases in public library funding allocation decisions have given little insight into the factors that motivate those politicians involved in the process and the variables that contribute to these decisions. No prior studies have examined the construct of influence in decision making about funding for Canadian public libraries at any level of government. Additionally, no prior studies have examined the construct of influence in decision making within the context of Canadian provincial politics. While many public libraries are facing difficult decisions in the face of uncertain funding futures, the ability of the sector to obtain favourable responses to requests for increases may require a less simplistic approach than previously thought. The ability to create meaningful connections with individuals in many communities and across all levels of government should be emphasised as a key factor in influencing funding decisions.

Association of the NuMA region on chromosome 11q13 with breast cancer susceptibility

The development of breast cancer is a complex process that involves multiple genes at many stages, from initial cell cycle dysregulation to disease progression. To identify genetic variations that influence this process, we conducted a large-scale association study using a collection of German cases and controls and >25,000 SNPs located within 16,000 genes. One of the loci identified was located on chromosome 11q13 [odds ratio (OR)=1.85, P=0.017]. The initial association was subsequently tested in two independent breast cancer collections. In both sample sets, the frequency of the susceptibility allele was increased in the cases (OR=1.6, P=0.01). The susceptibility allele was also associated with an increase in cancer family history (P=0.1). Fine mapping showed that the region of association extends approximately 300 kb and spans several genes, including the gene encoding the nuclear mitotic apparatus protein (NuMA). A nonsynonymous SNP (A794G) in NuMA was identified that showed a stronger association with breast cancer risk than the initial marker SNP (OR=2.8, P=0.005 initial sample; OR=2.1, P=0.002 combined). NuMA is a cell cycle-related protein essential for normal mitosis that is degraded in early apoptosis. NuMA-retinoic acid receptor alpha fusion proteins have been described in acute promyelocytic leukemia. Although the potential functional relevance of the A794G variation requires further biological validation, we conclude that variations in the NuMA gene are likely responsible for the observed increased breast cancer risk.

Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension

A polymorphism of the angiotensin I converting enzyme (ACE) gene has recently been reported and analysis of this polymorphism has indicated that it is associated with several cardiovascular diseases. However, the results are still controversial and such association has not yet been established conclusively. To determine whether the ACE gene may be responsible for essential hypertension in a Japanese population, we also compared the distribution of genotypes and the allele frequency of this polymorphism in our findings of a Japanese population with these features in other countries. Eighty-seven hypertensive patients with a family history of essential hypertension and 95 normotensive patients whose parents had no such history were enrolled in the study. Polymorphism of the ACE gene was determined by using the polymerase chain reaction. Homozygotes for this polymorphism had either a 490-bp band (II) or a 190-bp band (DD) and heterozygotes had both bands (ID). In hypertensive subjects, the numbers and frequency of the ACE genotypes were: II, 44 (0.51); ID, 26 (0.30); DD, 17 (0.19). In normotensive subjects these were: II, 35 (0.37); ID, 43 (0.45); DD, 17 (0.18). There were no significant differences between the two groups in derived allele frequencies (chi 2 = 1.41). The difference between the overall allelic frequency in Japan and that reported in several other countries was significant. We did not find any association between ACE gene polymorphism and essential hypertension in Japan. However, there were significant differences in derived allele frequencies between our findings in a Japanese population and those reported from Europe and Australia.

Marked association of a RFLP for the low density lipoprotein receptor gene with obesity in essential hypertensives

RFLPs at the low density lipoprotein receptor locus (LDLR) display marked linkage disequilibrium between each other. Cross-sectional analysis of a bi-alleleic ApaLI RFLP of LDLR showed that the 9.4- and 6.6-kb alleles were present in similar frequency between a group of 84 Caucasian essential hypertensive (HT) and a group of 96 normotensive subjects whose parents each had a similar blood pressure status at age > or = 50. After subdividing HTs into lean and obese, however, the frequency of the 6.6-kb allele in the 27 HTs with BMI > or = 26 kg/m2 was 0.63, compared with 0.39 for HTs with BMI < 26 (chi 2 = 8.8; P = 0.004). The difference in genotype frequencies was even more striking (chi 2 = 23; P = 0.00008), with a virtual absence of 9.4-kb homozygotes in the obese HT group (1 vs 22). Genetic variation at LDLR (19p13.2) is thus associated with obesity in HT.

Association of oestrogen-receptor gene (ESR1) polymorphisms with migraine in the large Norfolk Island pedigree

BACKGROUND: Oestrogen receptor 1 ( ESR1) is located in region 6q25.1 and encodes a ligand-activated transcription factor composed of several domains important for hormone binding and transcription activation. Progesterone receptor ( PGR) is located in 11q22-23 and mediates the role of progesterone interacting with different transcriptional co-regulators. ESR1 and PGR have previously been implicated in migraine susceptibility. Here, we report the results of an association study of these genes in a migraine pedigree from the genetic isolate of Norfolk Island, a population descended from a small number of Isle of Man "Bounty Mutineer" and Tahitian founders.

Association of a RFLP for the insulin receptor gene, but not insulin, with essential hypertension

Insulin has cardiovascular actions and patients with essential hypertension display insulin resistance. A cross-sectional study of the R1 RFLP of the insulin receptor gene (INSR) was carried out in 67 hypertensive (HT) and 75 normotensive (NT) subjects whose parents had a similar blood pressure status at age ≥50. The frequency of the minor (+) allele was 0.31 in HTs and 0.44 in NTs, and the difference between observed alleles in all subjects in each group was significant (χ2 = 4.8, P<0.05). Allele frequencies of a BglI RFLP of the insulin gene, however, did not differ between the HT and NT groups. The data thus provide evidence in favour of an association of HT with a polymorphism at the INSR locus (19p 13.3-13.2), so implicating this locus, and possibly a genetic variant of the insulin receptor itself, in HT.

Evidence for allelic association of the dopamine β-hydroxylase gene (DBH) with susceptibility to typical migraine

Migraine is a debilitating neurological disorder characterized by recurrent attacks of severe headache. The disorder is highly prevalent, affecting approximately 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the type and number of genes involved is not yet clear. However, the calcium channel gene, CACNA1A, on chromosome 19 contains mutations responsible for familial hemiplegic migraine, a rare and severe subtype of migraine. There is also evidence to suggest that serotonin- and dopamine-related genes may be involved in the pathogenesis of migraine. This study employed a linkage and association approach to investigate neurotransmitter-related migraine candidate genes. Polymorphisms within the dopamine beta-hydroxylase (DBH) gene, serotonin transporter gene (SERT), and dopamine receptor gene (DRD2) were tested in 177 unrelated Caucasian migraineurs and 182 control individuals. In addition, an independent sample of 82 families affected with migraine was examined. Unrelated case-control association analysis of a DBH intragenic dinucleotide polymorphism indicated altered allelic distribution between migraine and control groups (L2=16.53, P=0.019). Furthermore, the transmission/disequilibrium test, which was implemented on the family data, also indicated distortion of allele transmission for the same DBH marker (L2=4.44, P=0.035). Together, these results provide evidence for allelic association of the DBH gene with typical migraine susceptibility (Fisher's combined P value=0.006) and indicate that further research into the role of the DBH gene in the etiology of migraine is warranted.