Unusual cross-ring S(N)2 reactions of M-H (-) ions of methoxyacetanilides

Deprotonated o, m-, and p-methoxyacetanilide show pronounced peaks in their collision-induced tandem mass spectra (MS/MS) produced by losses of the elements of C2H6. It is proposed that this reaction is a 'cross-ring' internal S(N)2 reaction involving an incipient methyl anion. For example, p-CH3O-C6H4-N--CO-CH3--> [(p.CH3O-C6H4-N=C=O)CH3-]--> O---C6H4-N=C=O+C2H6.

Unusual cross-ring SN2 reactions of [MH]− ions of methoxyacetanilides

Deprotonated o, m-, and p-methoxyacetanilide show pronounced peaks in their collision-induced tandem mass spectra (MS/MS) produced by losses of the elements of C2H6. It is proposed that this reaction is a 'cross-ring' internal S(N)2 reaction involving an incipient methyl anion. For example, p-CH3O-C6H4-N--CO-CH3--> [(p.CH3O-C6H4-N=C=O)CH3-]--> O---C6H4-N=C=O+C2H6.

Law, ethics and pandemic preparedness : the importance of cross-jurisdictional and cross-cultural perspectives

OBJECTIVE To explore social equity, health planning, regulatory and ethical dilemmas in responding to a pandemic influenza (H5N1) outbreak, and the adequacy of protocols and standards such as the International Health Regulations (2005). APPROACH This paper analyses the role of legal and ethical considerations for pandemic preparedness, including an exploration of the relevance of cross-jurisdictional and cross-cultural perspectives in assessing the validity of goals for harmonisation of laws and policies both within and between nations. Australian and international experience is reviewed in various areas, including distribution of vaccines during a pandemic, the distribution of authority between national and local levels of government, and global and regional equity issues for poorer countries. CONCLUSION This paper finds that questions such as those of distributional justice (resource allocation) and regulatory frameworks raise important issues about the cultural and ethical acceptability of planning measures. Serious doubt is cast on a 'one size fits all' approach to international planning for managing a pandemic. It is concluded that a more nuanced approach than that contained in international guidelines may be required if an effective response is to be constructed internationally. IMPLICATIONS The paper commends the wisdom of reliance on 'soft law', international guidance that leaves plenty of room for each nation to construct its response in conformity with its own cultural and value requirements.

Law, ethics and pandemic preparedness : the importance of cross-jurisdictional and cross-cultural perspectives

Objective To explore social equity, health planning, regulatory and ethical dilemmas in responding to a pandemic influenza (H5N1) outbreak, and the adequacy of protocols and standards such as the International Health Regulations (2005). Approach This paper analyses the role of legal and ethical considerations for pandemic preparedness, including an exploration of the relevance of cross-jurisdictional and cross-cultural perspectives in assessing the validity of goals for harmonisation of laws and policies both within and between nations. Australian and international experience is reviewed in various areas, including distribution of vaccines during a pandemic, the distribution of authority between national and local levels of government, and global and regional equity issues for poorer countries. Conclusion This paper finds that questions such as those of distributional justice (resource allocation) and regulatory frameworks raise important issues about the cultural and ethical acceptability of planning measures. Serious doubt is cast on a ‘one size fits all’ approach to international planning for managing a pandemic. It is concluded that a more nuanced approach than that contained in international guidelines may be required if an effective response is to be constructed internationally. Implications The paper commends the wisdom of reliance on ‘soft law’, international guidance that leaves plenty of room for each nation to construct its response in conformity with its own cultural and value requirements.

Analysis of expressed sequence tags from Actinidia : Applications of a cross species EST database for gene discovery in the areas of flavor, health, color and ripening

Background Kiwifruit (Actinidia spp.) are a relatively new, but economically important crop grown in many different parts of the world. Commercial success is driven by the development of new cultivars with novel consumer traits including flavor, appearance, healthful components and convenience. To increase our understanding of the genetic diversity and gene-based control of these key traits in Actinidia, we have produced a collection of 132,577 expressed sequence tags (ESTs). Results The ESTs were derived mainly from four Actinidia species (A. chinensis, A. deliciosa, A. arguta and A. eriantha) and fell into 41,858 non redundant clusters (18,070 tentative consensus sequences and 23,788 EST singletons). Analysis of flavor and fragrance-related gene families (acyltransferases and carboxylesterases) and pathways (terpenoid biosynthesis) is presented in comparison with a chemical analysis of the compounds present in Actinidia including esters, acids, alcohols and terpenes. ESTs are identified for most genes in color pathways controlling chlorophyll degradation and carotenoid biosynthesis. In the health area, data are presented on the ESTs involved in ascorbic acid and quinic acid biosynthesis showing not only that genes for many of the steps in these pathways are represented in the database, but that genes encoding some critical steps are absent. In the convenience area, genes related to different stages of fruit softening are identified. Conclusion This large EST resource will allow researchers to undertake the tremendous challenge of understanding the molecular basis of genetic diversity in the Actinidia genus as well as provide an EST resource for comparative fruit genomics. The various bioinformatics analyses we have undertaken demonstrates the extent of coverage of ESTs for genes encoding different biochemical pathways in Actinidia.

Jumping the fence from dance to cross-disciplinary research

Introduction: reading the signs Inside the dance ethos, knowledge is rarely articulated other than through the experience of dance itself. On the surface, the dancer focuses on practical and specialist skills. However, a closer look reveals that their knowledge does not merely trigger an embodied way of thinking; it enables the dancer to map a trail of metaphors within the body. In effect, dancers acquire a distinct embodied culture with its own language, dialects, customs and traditions. In this paper, I shall firstly examine the way metaphors establish a link between reason and imagination between one set of embodied knowledge and another. It is in regards to this function, where metaphor welds opposites together or when interior and exterior information exist in the same moment that it is most useful for jumping the fence from dance to cross-disciplinary practice. Secondly, I shall discuss how metaphors can help sustain creative practice. For it is only by stepping outside the culture of dance that I could first unravel the experiences, processes and knowledges inscribed through a career in dance and begin to define the quality of my own voice.

Organizational factors impacting on patient satisfaction : a cross sectional examination of service climate and linkages to nurses' effort and performance

Background Patient satisfaction is influenced by the setting in which patients are treated and the employees providing care. However, to date, limited research has explained how health care organizations or nurses influence patient satisfaction. Objectives The purpose of this study was to test the model that service climate would increase the effort and performance of nursing groups and, in turn, increase patient satisfaction. Method This study incorporated data from 156 nurses, 28 supervisors, and 171 patients. A cross-sectional design was utilized to examine the relationship between service climate, nurse effort, nurse performance and patient satisfaction. Structural equation modeling was conducted to test the proposed relationships. Results Service climate was associated with the effort that nurses directed towards technical care and extra-role behaviors. In turn, the effort that nurses exerted predicted their performance, as rated by their supervisors. Finally, task performance was a significant predictor of patient satisfaction. Conclusions This study suggests that both hospital management and nurses play a role in promoting patient satisfaction. By focusing on creating a climate for service, health care managers can improve nursing performance and patient satisfaction with care.

Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction : a model for cross-modulation

Background A feature of epithelial to mesenchymal transition (EMT) relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC. Methods PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome. Results When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4). Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse correlation with lower expression values being predictive of increased risk. Conclusion ST in combination with EGF directed a greater EMT via actin depolymerisation and focal contact size reduction, resulting in a loosening of cell-ECM attachment along with Snail1-Zeb1/δEF1 induction. This appeared fundamentally different to the EGF-induced EMT, highlighting the multiple pathways which can regulate EMT. Our findings add support for a functional role for Snail1 in invasive breast cancer.

Depression and belongingness in general and workplace contexts : a cross-lagged longitudinal investigation

Belongingness has been linked to depression. Prior studies have been cross-sectional with few addressing distinct belongingness contexts. This study used structural equation modelling to investigate cross-lagged longitudinal relationships between general belonging, workplace belonging and depressive symptoms in a community sample of 221 working adults measured at two time points three months apart. Measures were: Sense of Belonging Instrument-Psychological (SOBI-P); Psychological Sense of Organizational Membership (PSOM); Depression Anxiety Stress Scales (DASS-21); Kessler Psychological Distress Scale (K10). General belonging was predicted more strongly by depressive symptoms than by baseline general belonging, suggesting that depressive symptoms not only linger but also influence future belongingness cognitions. Neither general nor workplace belonging longitudinally predicted depressive symptoms, however cross-sectional correlations were substantial. The concurrent path between general belongingness and depressive symptoms was strong. Results are consistent with daily process studies suggesting that reduced belongingness precipitates a rapid increase in depressive symptoms which influence longer term belongingness cognitions. Congruent with interpersonal descriptions of depression such as the social-cognitive interpersonal process model, results further suggest that belongingness cognitions are the proximal antecedent of a depressive response. Practitioners should monitor both a general sense of belonging as well as perceived relational value cues in specific contexts.

Invisible connections : investigating older people's emotions and social relations around objects

The advent of the Internet of Things creates an interest in how people might interrelate through and with networks of internet enabled objects. With an emphasis on fostering social connection and physical activity among older people, this preliminary study investigated objects that people over the age of 65 years viewed as significant to them. We conducted contextual interviews in people's homes about their significant objects in order to understand the role of the objects in their lives, the extent to which they fostered emotional and social connections and physical activity, and how they might be augmented through internet connection. Discussion of significant objects generated considerable emotion in the participants. We identified objects of comfort and routine, objects that exhibited status, those that fostered independence and connection, and those that symbolized relationships with loved ones. These findings lead us to consider implications for the design of interconnected objects.

Mechanics of microfilaments networks : a cross-scales study

The mechanical properties of microfilament networks are systematically summarized at different special scales in this paper. We have presented the mechanical models of single microfilaments and microfilament networks at microscale. By adopting a coarse-grained simulation strategy, the mechanical stability of microfilaments related cellular structures are analysed. Structural analysis is conducted to microfilament networks to understand the stress relaxation under compression. The nanoscale molecular mechanisms of the microfilaments deformation is also summarized from the viewpoint of molecular dynamics simulation. This paper provides the fundaments of multiscale modelling framework for the mechanical behaviours simulation of hierarchical microfilament networks.

Phagocytosis of cross-linked gelatin matrix by human breast carcinoma cells correlates with their invasive capacity

During invasion and metastasis, cancer cells interact closely with the extracellular matrix molecules by attachment, degradation, and migration. We demonstrated previously the local degradation of fluorescently labeled gelatin matrix by cancer cells at invasive membrane protrusions, called invadopodia. Using the newly developed quantitative fluorescence-activated cell sorting-phagocytosis assay and image analysis of localized degradation of fluorescently labeled matrix, we document here that degradation and site- specific removal of cross-linked gelatin matrix is correlated with the extent of phagocytosis in human breast cancer cells. A higher phagocytic capacity is generally associated with increasing invasiveness, documented in other invasion and motility assays as well. Gelatin phagocytosis is time and cell density dependent, and it is mediated by the actin cytoskeleton. Most of the intracellular gelatin is routed to actively acidified vesicles, as demonstrated by the fluorescent colocalization of gelatin with acidic vesicles, indicating the intracellular degradation of the phagocytosed matrix in lysosomes. We show here that normal intracellular routing is blocked after treatment with acidification inhibitors. In addition, the need for partial proteolytic degradation of the matrix prior to phagocytosis is demonstrated by the inhibition of gelatin phagocytosis with different serine and metalloproteinase inhibitors and its stimulation by conditioned medium containing the matrix metalloproteinases MMP-2 and MMP-9. Our results demonstrate that phagocytosis of extracellular matrix is an inherent feature of breast tumor cells that correlates with and may even directly contribute to their invasive capacity. This assay is useful for screening and evaluating potential anti-invasive agents because it is fast, reproducible, and versatile.

Reduced excision repair cross-complementing 1 expression associates with enhanced papilloma formation and fibroblast transformation after genetic disruption of secreted protein acidic and rich in cysteine

SPARC (secreted protein acidic and rich in cysteine)/ osteonectin/BM-40 is a matricellular protein implicated in development, cell transformation and tumorigenesis. We have examined the role of SPARC in cell transformation induced chemically with 7,12-dimethylbenz[a]anthracene (DMBA) and 12- tetradecanoylphorbol-13-acetate (TPA) in embryonic fibroblasts and in the skin of mice. Embryonic fibroblasts from SPARCnull mice showed increases in cell proliferation, enhanced sensitivity to DMBA and a higher number of DMBA/TPA-induced transformation foci. The number of DMBA-DNA adducts was 9 times higher in SPARCnull fibroblasts and their stability was lower than wild-type fibroblasts, consistent with a reduction in excision repair cross-complementing 1 the nucleotide excision repair enzyme in these cells. The SPARCnull mice showed an increase in both the speed and number of papillomas forming after topical administration of DMBA/TPA to the skin. These papillomas showed reduced growth and reduced progression to a more malignant phenotype, indicating that the effect of SPARC on tumorigenesis depends upon the transformation stage and/or tissue context. These data reinforce a growing number of observations in which SPARC has shown opposite effects on different tumor types/stages.

Practice and Procedures - Cross v Queensland Rugby Football Union Ltd [2001] QSC 173

The decision of Chesterman J in Cross v Queensland Rugby Football Union Ltd [2001] QSC 173 (Supreme Court of Queensland, No 3426 of 1997), Chesterman J, 30.5.2001) opens the possibilities for delivering interrogatories, particularly in the context of interrogatories relating to an opponent's version of events.