904 resultados para Protein P-1
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High magnification and large depth of field with a temporal resolution of less than 100 microseconds are possible using the present invention which combines a linear electron beam produced by a tungsten filament from an SX-40A Scanning Electron Microscope (SEM), a magnetic deflection coil with lower inductance resulting from reducing the number of turns of the saddle-coil wires, while increasing the diameter of the wires, a fast scintillator, photomultiplier tube, photomultiplier tube base, and signal amplifiers and a high speed data acquisition system which allows for a scan rate of 381 frames per second and 256.times.128 pixel density in the SEM image at a data acquisition rate of 25 MHz. The data acquisition and scan position are fully coordinated. A digitizer and a digital waveform generator which generates the sweep signals to the scan coils run off the same clock to acquire the signal in real-time.
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Context: It has been theorized that a positive Trendelenburg test (TT) indicates weakness of the stance hip-abductor (HABD) musculature, results in contralateral pelvic drop, and represents impaired load transfer, which may contribute to low back pain. Few studies have tested whether weakness of the HABDs is directly related to the magnitude of pelvic drop (MPD). Objective: To examine the relationship between HABD strength and MPD during the static TT and during walking for patients with nonspecific low back pain (NSLBP) and healthy controls (CON). A secondary purpose was to examine this relationship in NSLBP after a 3-wk HABD-strengthening program. Design: Quasi-experimental. Setting: Clinical research laboratory. Participants: 20 (10 NSLBP and 10 CON). Intervention: HABD strengthening. Main Outcome Measures: Normalized HABD strength, MPD during TT, and maximal pelvic frontal-plane excursion during walking. Results: At baseline, the NSLBP subjects were significantly weaker (31%; P = .03) than CON. No differences in maximal pelvic frontal-plane excursion (P = .72), right MPD (P = 1.00), or left MPD (P = .40) were measured between groups. During the static TT, nonsignificant correlations were found between left HABD strength and right MPD for NSLBP (r = -.32, P = .36) and CON (r = -.24, P = .48) and between right HABD strength and left MPD for NSLBP (r = -.24, P = .50) and CON (r = -.41, P = .22). Nonsignificant correlations were found between HABD strength and maximal pelvic frontal-plane excursion for NSLBP (r = -.04, P = .90) and CON (r = -.14, P = .68). After strengthening, NSLBP demonstrated significant increases in HABD strength (12%; P = .02), 48% reduction in pain, and no differences in MPD during static TT and maximal pelvic frontal-plane excursion compared with baseline. Conclusions: HABD strength was poorly correlated to MPD during the static TT and during walking in CON and NSLBP. The results suggest that HABD strength may not be the only contributing factor in controlling pelvic stability, and the static TT has limited use as a measure of HABD function.
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Vietnamese-Australians live in Australia, a large island continent. The physical contrast between Vietnam and Australia is remarked upon by many Vietnamese in their migration stories. Whereas Vietnam is remembered as an interlinked sensual and social world, Australia is often viewed as a harsh, spacious, empty, dry continent. Australia is located in a regional Asian context, but this location has always been culturally and politically problematic, as it historically attempted to define itself as a "white" European nation in the Southern Hemisphere(Ang, 2000, p. xiii; McNamara & Coughlan, 1997, p. 1). During the Gold Rush period in the late 1800s, when there was widespread opposition to Chinese labor, Australia implemented a "White Australia" policy, although there were historically a significant number of Australians of Asian background. This exclusionary immigration policy was effectively overturned in the 1970s with the acceptance of a large number of refugees from Vietnam, Cambodia, and Laos in 1975. Vietnamese-Australians live predominantly in urban areas with over three quarters living in Sydney and Melbourne, the two largest cities. Within these two cities they are also highly concentrated in ethnically diverse suburbs, most living in areas with more than 1,000 residents born in Vietnam (Viviani, 1996, p. 49). However, Jupp (Jupp et al., 1990; Jupp, 1993) has argued that these areas are also zones of transition, with much movement in and out...
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This paper focuses on a series of cookbooks published by Indigenous Australian groups. These cookbooks are typically produced with government funding, and are developed by nutritionists, dieticians, and health workers in consultation with local communities. They are designed to teach Indigenous Australians to cook healthy, nutritious, low-cost meals. In this paper, Fredericks and Anderson identify the value of these cookbooks as low-cost, public health interventions. However, they note that their value as health interventions has not been tested. Fredericks and Anderson question the value of these cookbooks within the broader context of the health disadvantage faced by Indigenous Australians. They argue that the cookbooks are developed from a Western perspective of health and nutrition that fails to recognise the value of traditional Indigenous foodways. They suggest that incorporating more Indigenous food knowledge and food-related traditions into cookbooks may be one way of improving health among Indigenous peoples and revitalising Indigenous knowledge.
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The representation of business process models has been a continuing research topic for many years now. However, many process model representations have not developed beyond minimally interactive 2D icon-based representations of directed graphs and networks, with little or no annotation for information overlays. In addition, very few of these representations have undergone a thorough analysis or design process with reference to psychological theories on data and process visualization. This dearth of visualization research, we believe, has led to problems with BPM uptake in some organizations, as the representations can be difficult for stakeholders to understand, and thus remains an open research question for the BPM community. In addition, business analysts and process modeling experts themselves need visual representations that are able to assist with key BPM life cycle tasks in the process of generating optimal solutions. With the rise of desktop computers and commodity mobile devices capable of supporting rich interactive 3D environments, we believe that much of the research performed in computer human interaction, virtual reality, games and interactive entertainment have much potential in areas of BPM; to engage, provide insight, and to promote collaboration amongst analysts and stakeholders alike. We believe this is a timely topic, with research emerging in a number of places around the globe, relevant to this workshop. This is the second TAProViz workshop being run at BPM. The intention this year is to consolidate on the results of last year's successful workshop by further developing this important topic, identifying the key research topics of interest to the BPM visualization community.
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BACKGROUND AND AIMS: Crohn's disease (CD) is an inflammatory bowel disease (IBD) caused by a combination of genetic, clinical, and environmental factors. Identification of CD patients at high risk of requiring surgery may assist clinicians to decide on a top-down or step-up treatment approach. METHODS: We conducted a retrospective case-control analysis of a population-based cohort of 503 CD patients. A regression-based data reduction approach was used to systematically analyse 63 genomic, clinical and environmental factors for association with IBD-related surgery as the primary outcome variable. RESULTS: A multi-factor model was identified that yielded the highest predictive accuracy for need for surgery. The factors included in the model were the NOD2 genotype (OR = 1.607, P = 2.3 × 10(-5)), having ever had perianal disease (OR = 2.847, P = 4 × 10(-6)), being post-diagnosis smokers (OR = 6.312, P = 7.4 × 10(-3)), being an ex-smoker at diagnosis (OR = 2.405, P = 1.1 × 10(-3)) and age (OR = 1.012, P = 4.4 × 10(-3)). Diagnostic testing for this multi-factor model produced an area under the curve of 0.681 (P = 1 × 10(-4)) and an odds ratio of 3.169, (95 % CI P = 1 × 10(-4)) which was higher than any factor considered independently. CONCLUSIONS: The results of this study require validation in other populations but represent a step forward in the development of more accurate prognostic tests for clinicians to prescribe the most optimal treatment approach for complicated CD patients.
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Migraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci. An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical α = 1×10−5) ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, P = 8.92×10−4), whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65×10−4). Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women’s Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P<0.05). Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.63×10−5) is located within the 5′UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.
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Objective: To perform a 1-stage meta-analysis of genome-wide association studies (GWAS) of multiple sclerosis (MS) susceptibility and to explore functional consequences of new susceptibility loci. Methods: We synthesized 7 MS GWAS. Each data set was imputed using HapMap phase II, and a per single nucleotide polymorphism (SNP) meta-analysis was performed across the 7 data sets. We explored RNA expression data using a quantitative trait analysis in peripheral blood mononuclear cells (PBMCs) of 228 subjects with demyelinating disease. Results: We meta-analyzed 2,529,394 unique SNPs in 5,545 cases and 12,153 controls. We identified 3 novel susceptibility alleles: rs170934T at 3p24.1 (odds ratio [OR], 1.17; p ¼ 1.6 � 10�8) near EOMES, rs2150702G in the second intron of MLANA on chromosome 9p24.1 (OR, 1.16; p ¼ 3.3 � 10�8), and rs6718520A in an intergenic region on chromosome 2p21, with THADA as the nearest flanking gene (OR, 1.17; p ¼ 3.4 � 10�8). The 3 new loci do not have a strong cis effect on RNA expression in PBMCs. Ten other susceptibility loci had a suggestive p < 1 � 10�6, some of these loci have evidence of association in other inflammatory diseases (ie, IL12B, TAGAP, PLEK, and ZMIZ1). Interpretation: We have performed a meta-analysis of GWAS in MS that more than doubles the size of previous gene discovery efforts and highlights 3 novel MS susceptibility loci. These and additional loci with suggestive evidence of association are excellent candidates for further investigations to refine and validate their role in the genetic architecture of MS.
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To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 x 10(-11); rs10876994, P = 2.7 x 10(-10); rs12368653, P = 1.0 x 10(-7)) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 x 10(-7); rs1569723, P = 2.9 x 10(-7)). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 x 10(-184); CD58, P = 9.6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).
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Vietnamese-Australians live in Australia, a large island continent. The physical contrast between Vietnam and Australia is remarked upon by many Vietnamese in their migration stories. Whereas Vietnam is remembered as an interlinked sensual and social world, Australia is often viewed as a harsh, spacious, empty, dry continent. Australia is located in a regional Asian context, but this location has always been culturally and politically problematic, as it historically attempted to define itself as a "white" European nation in the Southern Hemisphere (Ang, 2000, p. xiii; McNamara & Coughlan, 1997, p. 1). During the Gold Rush period in the late 1800s, when there was widespread opposition to Chinese labor, Australia implemented a "White Australia" policy, although there were historically a significant number of Australians of Asian background. This exclusionary immigration policy was effectively overturned in the 1970s with the acceptance of a large number of refugees from Vietnam, Cambodia, and Laos in 1975. Vietnamese-Australians live predominantly in urban areas with over three quarters living in Sydney and Melbourne, the two largest cities. Within these two cities they are also highly concentrated in ethnically diverse suburbs, most living in areas with more than 1,000 residents born in Vietnam (Viviani, 1996, p. 49). However, Jupp (Jupp et al., 1990; Jupp, 1993) has argued that these areas are also zones of transition, with much movement in and out.
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Background: Genome-wide association studies (GWAS) have identified more than 100 genetic loci for various cancers. However, only one is for endometrial cancer. Methods: We conducted a three-stage GWAS including 8,492 endometrial cancer cases and 16,596 controls. After analyzing 585,963 single-nucleotide polymorphisms (SNP) in 832 cases and 2,682 controls (stage I) from the Shanghai Endometrial Cancer Genetics Study, we selected the top 106 SNPs for in silico replication among 1,265 cases and 5,190 controls from the Australian/British Endometrial Cancer GWAS (stage II). Nine SNPs showed results consistent in direction with stage I with P < 0.1. These nine SNPs were investigated among 459 cases and 558 controls (stage IIIa) and six SNPs showed a direction of association consistent with stages I and II. These six SNPs, plus two additional SNPs selected on the basis of linkage disequilibrium and P values in stage II, were investigated among 5,936 cases and 8,166 controls from an additional 11 studies (stage IIIb). Results: SNP rs1202524, near the CAPN9 gene on chromosome 1q42.2, showed a consistent association with endometrial cancer risk across all three stages, with ORs of 1.09 [95% confidence interval (CI), 1.03–1.16] for the A/G genotype and 1.17 (95% CI, 1.05–1.30) for the G/G genotype (P = 1.6 × 10−4 in combined analyses of all samples). The association was stronger when limited to the endometrioid subtype, with ORs (95% CI) of 1.11 (1.04–1.18) and 1.21 (1.08–1.35), respectively (P = 2.4 × 10−5). Conclusions: Chromosome 1q42.2 may host an endometrial cancer susceptibility locus. Impact: This study identified a potential genetic locus for endometrial cancer risk
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Background: Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a survival factor in the disease. Methods: TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB 2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression. Results: TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB 2levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis. Conclusion: TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC. © 2011 Cathcart et al; licensee BioMed Central Ltd.
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Purpose Cancer cells have been shown to be more susceptible to Ran knockdown than normal cells. We now investigate whether Ran is a potential therapeutic target of cancers with frequently found mutations that lead to higher Ras/MEK/ERK [mitogen-activated protein/extracellular signal-regulated kinase (ERK; MEK)] and phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 activities. Experimental Design Apoptosis was measured by flow cytometry [propidium iodide (PI) and Annexin V staining] and MTT assay in cancer cells grown under different conditions after knockdown of Ran. The correlations between Ran expression and patient survival were examined in breast and lung cancers. Results Cancer cells with their PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways inhibited are less susceptible to Ran silencing-induced apoptosis. K-Ras-mutated, c-Met-amplified, and Pten-deleted cancer cells are also more susceptible to Ran silencing-induced apoptosis than their wild-type counterparts and this effect is reduced by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Overexpression of Ran in clinical specimens is significantly associated with poor patient outcome in both breast and lung cancers. This association is dramatically enhanced in cancers with increased c-Met or osteopontin expression, or with oncogenic mutations of K-Ras or PIK3CA, all of which are mutations that potentially correlate with activation of the PI3K/Akt/mTORC1 and/or Ras/MEK/ERK pathways. Silencing Ran also results in dysregulation of nucleocytoplasmic transport of transcription factors and downregulation of Mcl-1 expression, at the transcriptional level, which are reversed by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Conclusion Ran is a potential therapeutic target for treatment of cancers with mutations/changes of expression in protooncogenes that lead to activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. ©2011 AACR.
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Drosophila melanogaster, along with all insects and the vertebrates, lacks an RdRp gene. We created transgenic strains of Drosophila melanogaster in which the rrf-1 or ego-1 RdRp genes from C. elegans were placed under the control of the yeast GAL4 upstream activation sequence. Activation of the gene was performed by crossing these lines to flies carrying the GAL4 transgene under the control of various Drosophila enhancers. RT-PCR confirmed the successful expression of each RdRp gene. The resulting phenotypes indicated that introduction of the RdRp genes had no effect on D. melanogaster morphological development. © 2010 Springer Science+Business Media B.V.
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Background Physiotherapists are a professional group with a high rate of attrition and at high risk of musculoskeletal disorders. The purpose of this investigation was to examine the physical activity levels and health-related quality of life of physiotherapists working in metropolitan clinical settings in an Australian hospital and health service. It was hypothesized that practicing physiotherapists would report excellent health-related quality of life and would already be physically active. Such a finding would add weight to a claim that general physical activity conditioning strategies may not be useful for preventing musculoskeletal disorders among active healthy physiotherapists, but rather, future investigations should focus on the development and evaluation of role specific conditioning strategies. Methods A questionnaire was completed by 44 physiotherapists from three inpatient units and three ambulatory clinics (63.7% response rate). Physical activity levels were reported using the Active Australia Survey. Health-related quality of life was examined using the EQ-5D instrument. Physical activity and EQ-5D data were examined using conventional descriptive statistics; with domain responses for the EQ-5D presented in a frequency histogram. Results The majority of physiotherapists in this sample were younger than 30 years of age (n = 25, 56.8%) consistent with the presence of a high attrition rate. Almost all respondents exceeded minimum recommended physical activity guidelines (n = 40, 90.9%). Overall the respondents engaged in more vigorous physical activity (median = 180 minutes) and walking (median = 135 minutes) than moderate exercise (median = 35 minutes) each week. Thirty-seven (84.1%) participants reported no pain or discomfort impacting their health-related quality of life, with most (n = 35,79.5%) being in full health. Conclusions Physical-conditioning based interventions for the prevention of musculoskeletal disorders among practicing physiotherapists may be better targeted to role or task specific conditioning rather than general physical conditioning among this physically active population. It is plausible that an inherent attrition of physiotherapists may occur among those not as active or healthy as therapists who cope with the physical demands of clinical practice. Extrapolation of findings from this study may be limited due to the sample characteristics. However, this investigation addressed the study objectives and has provided a foundation for larger scale longitudinal investigations in this field.