Matrix metalloproteinase localisation by in situ-RT-PCR in archival human breast biopsy material

Utilising archival human breast cancer biopsy material we examined the stromal/epithelial interactions of several matrix metalloproteinases (MMPs) using in situ-RT-PCR (IS-RT-PCR). In breast cancer, the stromal/epithelial interactions that occur, and the site of production of these proteases, are central to understanding their role in invasive and metastatic processes. We examined MT1-MMP (MMP-14, membrane type-1-MMP), MMP-1 (interstitial collagenase) and MMP-3 (stromelysin-1) for their localisation profile in progressive breast cancer biopsy material (poorly differentiated invasive breast carcinoma (PDIBC), invasive breast carcinomas (IBC) and lymph node metastases (LNM)). Expression of MT1-MMP, MMP-1 and MMP-3 was observed in both the tumour epithelial and surrounding stromal cells in most tissue sections examined. MT1-MMP expression was predominantly localised to the tumour component in the pre-invasive lesions. MMP-1 gene expression was relatively well distributed between both tissue compartments, while MMP-3 demonstrated highest expression levels in the stromal tissue surrounding the epithelial tumour cells. The results demonstrate the ability to distinguish compartmental gene expression profiles using IS-RT-PCR. Further, we suggest a role for MT1-MMP in early tumour progression, expression of MMP-1 during metastasis and focal expression pattern of MMP-3 in areas of expansion. These expression profiles may provide markers for early breast cancer diagnoses and present potential therapeutic targets.

Novel NOD2 haplotype strengthens the association between TLR4 Asp299gly and Crohnʼs disease in an Australian population

Background:: The first major Crohn's disease (CD) susceptibility gene, NOD2, implicates the innate intestinal immune system and other pattern recognition receptors in the pathogenesis of this chronic, debilitating disorder. These include the Toll‐like receptors, specifically TLR4 and TLR5. A variant in the TLR4 gene (A299G) has demonstrated variable association with CD. We aimed to investigate the relationship between TLR4 A299G and TLR5 N392ST, and an Australian inflammatory bowel disease cohort, and to explore the strength of association between TLR4 A299G and CD using global meta‐analysis. Methods:: Cases (CD = 619, ulcerative colitis = 300) and controls (n = 360) were genotyped for TLR4 A299G, TLR5 N392ST, and the 4 major NOD2 mutations. Data were interrogated for case‐control analysis prior to and after stratification by NOD2 genotype. Genotype–phenotype relationships were also sought. Meta‐analysis was conducted via RevMan. Results:: The TLR4 A299G variant allele showed a significant association with CD compared to controls (P = 0.04) and a novel NOD2 haplotype was identified which strengthened this (P = 0.003). Furthermore, we identified that TLR4 A299G was associated with CD limited to the colon (P = 0.02). In the presence of the novel NOD2 haplotype, TLR4 A299G was more strongly associated with colonic disease (P < 0.001) and nonstricturing disease (P = 0.009). A meta‐analysis of 11 CD cohorts identified a 1.5‐fold increase in risk for the variant TLR4 A299G allele (P < 0.00001). Conclusions:: TLR 4 A299G appears to be a significant risk factor for CD, in particular colonic, nonstricturing disease. Furthermore, we identified a novel NOD2 haplotype that strengthens the relationship between TLR4 A299G and these phenotypes.

GEF-H1-RhoA signaling pathway mediates LPS-induced NF-κB transactivation and IL-8 synthesis in endothelial cells

Secretion of proinflammatory cytokines by LPS activated endothelial cells contributes substantially to the pathogenesis of sepsis. However, the mechanism involved in this process is not well understood. In the present study, we determined the roles of GEF-H1 (Guanine-nucleotide exchange factor-H1)-RhoA signalling in LPS-induced interleukin-8 (IL-8, CXCL8) production in endothelial cells. First, we observed that GEF-H1 expression was upregulated in a dose- and time-dependent manner as consistent with TLR4 (Toll-like receptor 4) expression after LPS stimulation. Afterwards, Clostridium difficile toxin B-10463 (TcdB-10463), an inhibitor of Rho activities, reduced LPS-induced NF-κB phosphorylation. Inhibition of GEF-H1 and RhoA expression reduced LPS-induced NF-κB and p38 phosphorylation. TLR4 knockout blocked LPS-induced activity of RhoA, however, MyD88 knockout did not impair the LPS-induced activity of RhoA. Nevertheless, TLR4 and MyD88 knockout both significantly inhibited transactivation of NF-κB. GEF-H1-RhoA and MyD88 both induced significant changes in NF-κB transactivation and IL-8 synthesis. Co-inhibition of GEF-H1-RhoA and p38 expression produced similar inhibitory effects on LPS-induced NF-κB transactivation and IL-8 synthesis as inhibition of p38 expression alone, thus confirming that activation of p38 was essential for the GEF-H1-RhoA signalling pathway to induce NF-κB transactivation and IL-8 synthesis. Taken together, these results demonstrate that LPS-induced NF-κB activation and IL-8 synthesis in endothelial cells are regulated by the MyD88 pathway and GEF-H1-RhoA pathway.

Destination marketing organizations and destination marketing : a narrative analysis of the literature

This article presents the first narrative analysis of the areas of research that have developed within the destination marketing field since its commencement in 1973. Given the broad extent of the field, and the absence of any previous reviews in four decades, a key challenge is in providing a focus for such a disparate body of knowledge. The review is structured around one principal question: ‘To what extent is the Destination Marketing Organisation (DMO) responsible for the competitiveness of the destination’? In pursuit of this underlying question, we address a number of themes including nomenclature and the DMO, the evolution of the destination marketing literature, competitiveness as the DMO reason d’être, and DMO effectiveness including issues of branding and positioning, and future research themes in the field.

Electrospinning and crosslinking of low-molecular-weight poly(trimethylene carbonate-co-L-lactide) as an elastomeric scaffold for vascular engineering

The growth of suitable tissue to replace natural blood vessels requires a degradable scaffold material that is processable into porous structures with appropriate mechanical and cell growth properties. This study investigates the fabrication of degradable, crosslinkable prepolymers of l-lactide-co-trimethylene carbonate into porous scaffolds by electrospinning. After crosslinking by γ-radiation, dimensionally stable scaffolds were obtained with up to 56% trimethylene carbonate incorporation. The fibrous mats showed Young’s moduli closely matching human arteries (0.4–0.8 MPa). Repeated cyclic extension yielded negligible change in mechanical properties, demonstrating the potential for use under dynamic physiological conditions. The scaffolds remained elastic and resilient at 30% strain after 84 days of degradation in phosphate buffer, while the modulus and ultimate stress and strain progressively decreased. The electrospun mats are mechanically superior to solid films of the same materials. In vitro, human mesenchymal stem cells adhered to and readily proliferated on the three-dimensional fiber network, demonstrating that these polymers may find use in growing artificial blood vessels in vivo.

Mainstreaming climate change adaptation : An incremental approach to disaster risk management in Australia

In this paper we argue that rationalist ‘predict then act’ approaches to disaster risk management (DRM) policy promote unrealistic public expectations of DRM provisions, the avoidance of decision making by political elites, an over-reliance on technical expertise and engineering solutions to reducing exposure to natural events, and a reactive approach to DRM overall. We propose an alternative incrementalist approach that focuses on managing uncertainties rather than reducing them and building resilience not simply through the reduction of hazard exposure, but also through the ongoing reduction of community vulnerability, the explicit consideration of normative priorities, and more effective community engagement in climate risk debates.

Separable and non-separable discrete wavelet transform based texture features and image classification of breast thermograms

Highly sensitive infrared cameras can produce high-resolution diagnostic images of the temperature and vascular changes of breasts. Wavelet transform based features are suitable in extracting the texture difference information of these images due to their scale-space decomposition. The objective of this study is to investigate the potential of extracted features in differentiating between breast lesions by comparing the two corresponding pectoral regions of two breast thermograms. The pectoral regions of breastsare important because near 50% of all breast cancer is located in this region. In this study, the pectoral region of the left breast is selected. Then the corresponding pectoral region of the right breast is identified. Texture features based on the first and the second sets of statistics are extracted from wavelet decomposed images of the pectoral regions of two breast thermograms. Principal component analysis is used to reduce dimension and an Adaboost classifier to evaluate classification performance. A number of different wavelet features are compared and it is shown that complex non-separable 2D discrete wavelet transform features perform better than their real separable counterparts.

Impairment of simulated motorcycle riding performance under low dose alcohol

Crash statistics that include the blood alcohol concentration (BAC) of vehicle operators reveal that crash involved motorcyclists are over represented at low BACs (e.g., ≤0.05%). This riding simulator study compared riding performance and hazard response under three low dose alcohol conditions (sober, 0.02% BAC, 0.05% BAC). Forty participants (20 novice, 20 experienced) completed simulated rides in urban and rural scenarios while responding to a safety-critical peripheral detection task (PDT). Results showed a significant increase in the standard deviation of lateral position in the urban scenario and PDT reaction time in the rural scenario under 0.05% BAC compared with zero alcohol. Participants were most likely to collide with an unexpected pedestrian in the urban scenario at 0.02% BAC, with novice participants at a greater relative risk than experienced riders. Novices chose to ride faster than experienced participants in the rural scenario regardless of BAC. Not all results were significant, emphasising the complex situation of the effects of low dose BAC on riding performance, which needs further research. The results of this simulator study provide some support for a legal BAC for motorcyclists below 0.05%.

Comparative study on the protective effects of Yinchenhao Decoction against liver injury induced by alpha-naphthylisothiocyanate and carbon tetrachloride

OBJECTIVE: To optimize the animal model of liver injury that can properly represent the pathological characteristics of dampness-heat jaundice syndrome of traditional Chinese medicine. METHODS: The liver injury in the model rat was induced by alpha-naphthylisothiocyanate (ANIT) and carbon tetrachloride (CCl(4) ) respectively, and the effects of Yinchenhao Decoction (, YCHD), a proved effective Chinese medical formula for treating the dampness-heat jaundice syndrome in clinic, on the two liver injury models were evaluated by analyzing the serum level of alanine aminotransferase (ALT), asparate aminotransferase (AST), alkaline phosphatase (ALP), malondialchehyche (MDA), total bilirubin (T-BIL), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) as well as the ratio of liver weight to body weight. The experimental data were analyzed by principal component analytical method of pattern recognition. RESULTS: The ratio of liver weight to body weight was significantly elevated in the ANIT and CCl(4) groups when compared with that in the normal control (P<0.01). The contents of ALT and T-BIL were significantly higher in the ANIT group than in the normal control (P<0.05,P<0.01), and the levels of AST, ALT and ALP were significantly elevated in CCl(4) group relative to those in the normal control P<0.01). In the YCHD group, the increase in AST, ALT and ALP levels was significantly reduced (P<0.05, P<0.01), but with no significant increase in serum T-BIL. In the CCl(4) intoxicated group, the MDA content was significantly increased and SOD, GSH-PX activities decreased significantly compared with those in the normal control group, respectively (P<0.01). The increase in MDA induced by CCl(4) was significantly reduced by YCHD P<0.05). CONCLUSION: YCHD showed significant effects on preventing liver injury progression induced by CCl(4), and the closest or most suitable animal model for damp-heat jaundice syndrome may be the one induced by CCl(4).

Anodic formation of a thick three-dimensional nanoporous WO3 film and its photocatalytic property

We report an efficient solar-light-driven photocatalyst based on three-dimensional nanoporous tungsten trioxide (WO3) films. These films are obtained by anodizing W foils in fluoride-containing electrolytes at room temperature and under low applied voltages with an efficient growth rate of 2 μm h− 1. The maximum thickness of the films is ~ 3 μm that exceeds those of previously reported anodized WO3 films in fluoride-containing electrolytes. By investigating the photocatalytic properties of the films with thicknesses ranging from ~ 0.5 to ~ 3 μm, the optimum thickness of the nanoporous film is found to be ~ 1 μm, which demonstrates an impressive 120% improvement in the photocatalytic performance compared to that of a RF-sputtered nanotextured film with similar weights. We mainly ascribe this to large surface area and smaller bandgap.

Direct electrochemical formation of alloyed AuPt nanostructured electrocatalysts for the oxidation of formic acid

The formation of highly anisotropic AuPt alloys has been achieved via a simple electrochemical approach without the need for organic surfactants to direct the growth process. The surface and bulk properties of these materials were characterised by scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX) and electrochemically by cyclic voltammetry to confirm alloy formation. It was found that AuPt materials are highly active for both the model hydrogen evolution reaction and the fuel cell relevant formic acid oxidation reaction. In particular for the latter case the preferred dehydrogenation pathway was observed at AuPt compared to nanostructured Pt prepared under identical electrochemical conditions which demonstrated the less preferred dehydration pathway. The enhanced performance is attributed to both the ensemble effect which facilitates CO(ads) removal from the surface as well as the highly anisotropic nanostructure of AuPt.

Estimation of disability weights on malignant neoplasms in Shandong province [山东省现患恶性肿瘤残疾权重的测量]

Objective To determine stage-specific and average disability weights (DWs) of malignant neoplasm and provide support and evidence for study on burden of cancer and policy development in Shandong province. Methods Health status of each cancer patient identified during the cancer prevalence survey in Shandong, 2007 was investigated. In line with the GBD methodology in estimating DWs, the disability extent of every case was classified and evaluated according to the Six-class Disability Classification version and then the stage-specific weights and average DWs with their 95 % confidence intervals were calculated, using SAS software. Results A total of 11 757 cancer cases were investigated and evaluated. DWs of specific stage of therapy, remission, metastasis and terminal of all cancers were 0.310, 0.218, 0.450 and 0.653 respectively. The average DW of all cancers was 0.317(95 % CI:0.312-0.321). Weights of different stage and different cancer varied significantly, while no significant differences were found between males and females. DWs were found higher (>0.4) for liver cancer, bone cancer, lymphoma and pancreas cancer. Lower DWs (<0.3) were found for breast cancer, cervix uteri, corpus uteri, ovarian cancer, larynx cancer, mouth and oropharynx cancer. Conclusion Stage-specific and average DWs for various cancers were estimated based on a large sample size survey. The average DWs of 0.317 for all cancers indicated that 1/3 healthy year lost for each survived life year of them. The difference of DWs between different cancer and stage provide scientific evidence for cancer prevention strategy development. Abstract in Chinese 目的 测算各种恶性肿瘤的分病程残疾权重和平均残疾权重,为山东省恶性肿瘤疾病负担研究及肿瘤防治对策制定提供参考依据. 方法 在山东省2007年恶性肿瘤现患调查中对所有恶性肿瘤患者的健康状况进行调查,参考全球疾病负担研究的方法 ,利用六级社会功能分级标准对患者残疾状况进行分级和赋值,分别计算20种恶性肿瘤的分病程残疾权重和平均残疾权重及其95%CI. 结果 共调查恶性肿瘤患者11757例,所有恶性肿瘤治疗期、恢复期、转移期和晚期的残疾权重分别为0.310、0.218、0.450和0.653,平均残疾权重为0.317(95%CI:0.312～0.321).不同恶性肿瘤和不同病程阶段的残疾权重差别显著,性别间差异无统计学意义.肝癌、骨癌、淋巴瘤和胰腺癌平均残疾权重较高(>0.4),乳腺癌、子宫体癌、子宫颈癌、卵巢癌、喉癌和口咽部癌症相对较低(<0.3). 结论 山东省恶性肿瘤平均残疾权重为0.317,即恶性肿瘤患者每存活1年平均损失近1/3个健康生命年;不同恶性肿瘤和不同病程阶段的残疾权重差别为肿瘤防治对策的制定具有重要意义.

Commencing nursing students' perceptions and anxiety of bioscience

It is known that bioscience is perceived to be difficult and causes anxiety within undergraduate nursing students; yet, commencing students' perceptions of bioscience is not known. Therefore, the aim of this study was to ascertain incoming students' perceptions, knowledge and approaches to learning bioscience. Incoming students to the Bachelor of Nursing completed a questionnaire prior to undertaking bioscience. Two hundred and seventy three students completed the questionnaire that explored their expectations, preconceptions of bioscience content, approaches to learning bioscience, and relationship to clinical practice in the context of biosciences. Participant ages ranged from 17 to 53 (mean 23 years), and 78% of students had completed at least one secondary school science subject, of which 60% had studied biology. Overall, students' preconceptions included anxiety about studying bioscience, bioscience being difficult and harder than nursing subjects, and that more content will be required for bioscience than nursing subjects. Analysis using ANOVA revealed the relationships for secondary school science and age on student responses. A significant effect of secondary school science was found for science in school being advantageous for bioscience (p = 0.010), understanding what bioscience entails (p = 0.002), needing to study science prior to the start of the semester (p = 0.009), and that bioscience is considered difficult (p = 0.029). A significant effect of age was found for exams being more difficult than other assessments (p = 0.000) and for being able to see the relevance of nursing when reaching the workplace (p = 0.011). The findings also indicated that perceptions and associated anxieties related to bioscience were present in commencing students, similar to those which have been reported previously in established student groups. This strongly suggests that the faculty should attempt to dispel preconceptions about bioscience and target improved supports to facilitate the transition of students into the commencement of bioscience for nursing students.

Recent developments and research needs in modeling lane changing

This paper comprehensively reviews recent developments in modeling lane-changing behavior. The major lane changing models in the literature are categorized into two groups: models that aim to capture the lane changing decision-making process, and models that aim to quantify the impact of lane changing behavior on surrounding vehicles. The methodologies and important features (including their limitations) of representative models in each category are outlined and discussed. Future research needs are determined.

Graphene ripples generated by grain boundaries in highly ordered pyrolytic graphite

Atomic scale periodic ripples that extend for several nanometers on the surface of adjacent graphitic grains have been observed for the first time on highly ordered pyrolitic graphite by UHV-STM. The ripples emanate from a grain boundary, and are explained in terms of a mechanical deformation due to the elastic strain accumulated along the GB, which is relieved out-of-plane in the topmost graphene layer. We present a molecular dynamics model that accounts for the formation of similar ripples as result of the lattice mismatch induced by two different grain orientations.