Studies of granulosa cell maturation in dominant and subordinate bovine follicles : novel extracellular matrix focimatrix is co-ordinately regulated with cholesterol side-chain cleavage CYP11A1

During growth of antral ovarian follicles granulosa cells first become associated with a novel type of extracellular matrix, focimatrix, and at larger sizes follicles become either subordinate or dominant. To examine this, bovine subordinate (9.0±s.e.m. 0.4 mm; n=16), partially dominant (12.0±0.6 mm; n=18) and fully dominant (15.0±0.4 mm; n=14) follicles were examined by real time RT-PCR analyses of granulosa cells and by immunohistochemistry of focimatrix. Changes in the expression of FSH receptor, LH receptor, cholesterol side-chain cleavage (CYP11A1), 3β-hydroxysteroid dehydrogenase, aromatase (CYP19A1) and inhibin-α and β-B were observed as expected for follicle sizes examined. After adjusting for size differences, only CYP11A1 was significantly different between the groups, and elevated in dominant follicles. Also after adjusting for differences in size there were no significant differences in expression of focimatrix components collagen type IV α-1 (COL4A1), laminin β-2, nidogen 1 (NID1), and perlecan (HSPG2) or the volume density of NID1 and -2 and HSPG2. The volume density of focimatrix components in laminin 111 was significantly elevated in dominant follicles. Adjusting for analysis of more than one follicle per animal and for multiple correlations, CYP11A1 mRNA levels were highly correlated with the focimatrix genes COL4A1, NID1 and -2 and HSPG2. Thus, focimatrix may potentially regulate CYP11A1 expression, and the regulation of both could be important in follicular dominance.

Stochastic analysis of the VEGF receptor response curve

Recently, an analysis of the response curve of the vascular endothelial growth factor (VEGF) receptor and its application to cancer therapy was described in [T. Alarcón, and K. Page, J. R. Soc. Lond. Interface 4, 283–304 (2007)]. The analysis is significantly extended here by demonstrating that an alternative computational strategy, namely the Krylov FSP algorithm for the direct solution of the chemical master equation, is feasible for the study of the receptor model. The new method allows us to further investigate the hypothesis of symmetry in the stochastic fluctuations of the response. Also, by augmenting the original model with a single reversible reaction we formulate a plausible mechanism capable of realizing a bimodal response, which is reported experimentally but which is not exhibited by the original model. The significance of these findings for mechanisms of tumour resistance to antiangiogenic therapy is discussed.

Frequency response function based structural damage detection using artificial neural networks

Damage detection in structures has become increasingly important in recent years. While a number of damage detection and localization methods have been proposed, few attempts have been made to explore the structure damage with frequency response functions (FRFs). This paper illustrates the damage identification and condition assessment of a beam structure using a new frequency response functions (FRFs) based damage index and Artificial Neural Networks (ANNs). In practice, usage of all available FRF data as an input to artificial neural networks makes the training and convergence impossible. Therefore one of the data reduction techniques Principal Component Analysis (PCA) is introduced in the algorithm. In the proposed procedure, a large set of FRFs are divided into sub-sets in order to find the damage indices for different frequency points of different damage scenarios. The basic idea of this method is to establish features of damaged structure using FRFs from different measurement points of different sub-sets of intact structure. Then using these features, damage indices of different damage cases of the structure are identified after reconstructing of available FRF data using PCA. The obtained damage indices corresponding to different damage locations and severities are introduced as input variable to developed artificial neural networks. Finally, the effectiveness of the proposed method is illustrated and validated by using the finite element modal of a beam structure. The illustrated results show that the PCA based damage index is suitable and effective for structural damage detection and condition assessment of building structures.

An analytical and experimental study of the vibration response of a clamped ribbed plate

An analytical solution is presented in this paper for the vibration response of a ribbed plate clamped on all its boundary edges by employing a travelling wave solution. A clamped ribbed plate test rig is also assembled in this study for the experimental investigation of the ribbed plate response and to provide verification results to the analytical solution. The dynamic characteristics and mode shapes of the ribbed plate are measured and compared to those obtained from the analytical solution and from finite element analysis (FEA). General good agreements are found between the results. Discrepancies between the computational and experimental results at low and high frequencies are also discussed. Explanations are offered in the study to disclose the mechanism causing the discrepancies. The dependency of the dynamic response of the ribbed plate on the distance between the excitation force and the rib is also investigated experimentally. It confirms the findings disclosed in a previous analytical study [T. R. Lin and J. Pan, A closed form solution for the dynamic response of finite ribbed plates. Journal of the Acoustical Society of America 119 (2006) 917-925] that the vibration response of a clamped ribbed plate due to a point force excitation is controlled by the plate stiffness when the source is more than a quarter plate bending wavelength away from the rib and from the plate boundary. The response is largely affected by the rib stiffness when the source location is less than a quarter bending wavelength away from the rib.

Shear in reinforced and unreinforced masonry : response, design and construction

This paper describes the vulnerability of masonry under shear; first the mechanisms of in-plane and out-of-plane shear performance of masonry are reviewed; both the unreinforced and lightly reinforced masonry wall systems are considered. Factors affecting the response of unreinforced and reinforced masonry to shear are described and the effect of the variability of those factors to the failure mode of masonry shear walls is also discussed. Some critique is provided on the existing design provisions in various masonry standards.

Intention, foresight and ending life : a response to "The Double Effect effect" by Charles Foster, Jonathan Herring, Karen Melham and Tony Hope, (CQ 20(1))

In this paper I examine the recent arguments by Charles Foster, Jonathan Herring, Karen Melham and Tony Hope against the utility of the doctrine of double effect. One basis on which they reject the utility of the doctrine is their claim that it is notoriously difficult to apply what they identify as its 'core' component, namely, the distinction between intention and foresight. It is this contention that is the primarily focus of my article. I argue against this claim that the intention/foresight distinction remains a fundamental part of the law in those jurisdictions where intention remains an element of the offence of murder and that, accordingly, it is essential ro resolve the putative difficulties of applying the intention/foresight distinction so as to ensure the integrity of the law of murder. I argue that the main reasons advanced for the claim that the intention/foresight distinction is difficult to apply are ultimately unsustainable, and that the distinction is not as difficult to apply as the authors suggest.

Photochemistry and chemometrics : an overview

Photochemistry has made significant contributions to our understanding of many important natural processes as well as the scientific discoveries of the man-made world. The measurements from such studies are often complex and may require advanced data interpretation with the use of multivariate or chemometrics methods. In general, such methods have been applied successfully for data display, classification, multivariate curve resolution and prediction in analytical chemistry, environmental chemistry, engineering, medical research and industry. However, in photochemistry, by comparison, applications of such multivariate approaches were found to be less frequent although a variety of methods have been used, especially with spectroscopic photochemical applications. The methods include Principal Component Analysis (PCA; data display), Partial Least Squares (PLS; prediction), Artificial Neural Networks (ANN; prediction) and several models for multivariate curve resolution related to Parallel Factor Analysis (PARAFAC; decomposition of complex responses). Applications of such methods are discussed in this overview and typical examples include photodegradation of herbicides, prediction of antibiotics in human fluids (fluorescence spectroscopy), non-destructive in- and on-line monitoring (near infrared spectroscopy) and fast-time resolution of spectroscopic signals from photochemical reactions. It is also quite clear from the literature that the scope of spectroscopic photochemistry was enhanced by the application of chemometrics. To highlight and encourage further applications of chemometrics in photochemistry, several additional chemometrics approaches are discussed using data collected by the authors. The use of a PCA biplot is illustrated with an analysis of a matrix containing data on the performance of photocatalysts developed for water splitting and hydrogen production. In addition, the applications of the Multi-Criteria Decision Making (MCDM) ranking methods and Fuzzy Clustering are demonstrated with an analysis of water quality data matrix. Other examples of topics include the application of simultaneous kinetic spectroscopic methods for prediction of pesticides, and the use of response fingerprinting approach for classification of medicinal preparations. In general, the overview endeavours to emphasise the advantages of chemometrics' interpretation of multivariate photochemical data, and an Appendix of references and summaries of common and less usual chemometrics methods noted in this work, is provided. Crown Copyright © 2010.

Policy analysis of disaster health management in China

Humankind has been dealing with all kinds of disasters since the dawn of time. The risk and impact of disasters producing mass casualties worldwide is increasing, due partly to global warming as well as to increased population growth, increased density and the aging population. China, as a country with a large population, vast territory, and complex climatic and geographical conditions, has been plagued by all kinds of disasters. Disaster health management has traditionally been a relatively arcane discipline within public health. However, SARS, Avian Influenza, and earthquakes and floods, along with the need to be better prepared for the Olympic Games in China has brought disasters, their management and their potential for large scale health consequences on populations to the attention of the public, the government and the international community alike. As a result significant improvements were made to the disaster management policy framework, as well as changes to systems and structures to incorporate an improved disaster management focus. This involved the upgrade of the Centres for Disease Control and Prevention (CDC) throughout China to monitor and better control the health consequences particularly of infectious disease outbreaks. However, as can be seen in the Southern China Snow Storm and Wenchuan Earthquake in 2008, there remains a lack of integrated disaster management and efficient medical rescue, which has been costly in terms of economics and health for China. In the context of a very large and complex country, there is a need to better understand whether these changes have resulted in effective management of the health impacts of such incidents. To date, the health consequences of disasters, particularly in China, have not been a major focus of study. The main aim of this study is to analyse and evaluate disaster health management policy in China and in particular, its ability to effectively manage the health consequences of disasters. Flood has been selected for this study as it is a common and significant disaster type in China and throughout the world. This information will then be used to guide conceptual understanding of the health consequences of floods. A secondary aim of the study is to compare disaster health management in China and Australia as these countries differ in their length of experience in having a formalised policy response. The final aim of the study is to determine the extent to which Walt and Gilson’s (1994) model of policy explains how disaster management policy in China was developed and implemented after SARS in 2003 to the present day. This study has utilised a case study methodology. A document analysis and literature search of Chinese and English sources was undertaken to analyse and produce a chronology of disaster health management policy in China. Additionally, three detailed case studies of flood health management in China were undertaken along with three case studies in Australia in order to examine the policy response and any health consequences stemming from the floods. A total of 30 key international disaster health management experts were surveyed to identify fundamental elements and principles of a successful policy framework for disaster health management. Key policy ingredients were identified from the literature, the case-studies and the survey of experts. Walt and Gilson (1994)’s policy model that focuses on the actors, content, context and process of policy was found to be a useful model for analysing disaster health management policy development and implementation in China. This thesis is divided into four parts. Part 1 is a brief overview of the issues and context to set the scene. Part 2 examines the conceptual and operational context including the international literature, government documents and the operational environment for disaster health management in China. Part 3 examines primary sources of information to inform the analysis. This involves two key studies: • A comparative analysis of the management of floods in China and Australia • A survey of international experts in the field of disaster management so as to inform the evaluation of the policy framework in existence in China and the criteria upon which the expression of that policy could be evaluated Part 4 describes the key outcomes of this research which include: • A conceptual framework for describing the health consequences of floods • A conceptual framework for disaster health management • An evaluation of the disaster health management policy and its implementation in China. The research outcomes clearly identified that the most significant improvements are to be derived from improvements in the generic management of disasters, rather than the health aspects alone. Thus, the key findings and recommendations tend to focus on generic issues. The key findings of this research include the following: • The health consequences of floods may be described in terms of time as ‘immediate’, ‘medium term’ and ‘long term’ and also in relation to causation as ‘direct’ and ‘indirect’ consequences of the flood. These two aspects form a matrix which in turn guides management responses. • Disaster health management in China requires a more comprehensive response throughout the cycle of prevention, preparedness, response and recovery but it also requires a more concentrated effort on policy implementation to ensure the translation of the policy framework into effective incident management. • The policy framework in China is largely of international standard with a sound legislative base. In addition the development of the Centres for Disease Control and Prevention has provided the basis for a systematic approach to health consequence management. However, the key weaknesses in the current system include: o The lack of a key central structure to provide the infrastructure with vital support for policy development, implementation and evaluation. o The lack of well-prepared local response teams similar to local government based volunteer groups in Australia. • The system lacks structures to coordinate government action at the local level. The result of this is a poorly coordinated local response and lack of clarity regarding the point at which escalation of the response to higher levels of government is advisable. These result in higher levels of risk and negative health impacts. The key recommendations arising from this study are: 1. Disaster health management policy in China should be enhanced by incorporating disaster management considerations into policy development, and by requiring a disaster management risk analysis and disaster management impact statement for development proposals. 2. China should transform existing organizations to establish a central organisation similar to the Federal Emergency Management Agency (FEMA) in the USA or the Emergency Management Australia (EMA) in Australia. This organization would be responsible for leading nationwide preparedness through planning, standards development, education and incident evaluation and to provide operational support to the national and local government bodies in the event of a major incident. 3. China should review national and local plans to reflect consistency in planning, and to emphasize the advantages of the integrated planning process. 4. Enhance community resilience through community education and the development of a local volunteer organization. China should develop a national strategy which sets direction and standards in regard to education and training, and requires system testing through exercises. Other initiatives may include the development of a local volunteer capability with appropriate training to assist professional response agencies such as police and fire services in a major incident. An existing organisation such as the Communist Party may be an appropriate structure to provide this response in a cost effective manner. 5. Continue development of professional emergency services, particularly ambulance, to ensure an effective infrastructure is in place to support the emergency response in disasters. 6. Funding for disaster health management should be enhanced, not only from government, but also from other sources such as donations and insurance. It is necessary to provide a more transparent mechanism to ensure the funding is disseminated according to the needs of the people affected. 7. Emphasis should be placed on prevention and preparedness, especially on effective disaster warnings. 8. China should develop local disaster health management infrastructure utilising existing resources wherever possible. Strategies for enhancing local infrastructure could include the identification of local resources (including military resources) which could be made available to support disaster responses. It should develop operational procedures to access those resources. Implementation of these recommendations should better position China to reduce the significant health consequences experienced each year from major incidents such as floods and to provide an increased level of confidence to the community about the country’s capacity to manage such events.

Modulation of the Chlamydia trachomatis In vitro transcriptome response by the sex hormones estradiol and progesterone

BACKGROUND:Chlamydia trachomatis is a major cause of sexually transmitted disease in humans. Previous studies in both humans and animal models of chlamydial genital tract infection have suggested that the hormonal status of the genital tract epithelium at the time of exposure can influence the outcome of the chlamydial infection. We performed a whole genome transcriptional profiling study of C. trachomatis infection in ECC-1 cells under progesterone or estradiol treatment.RESULTS:Both hormone treatments caused a significant shift in the sub-set of genes expressed (25% of the transcriptome altered by more than 2-fold). Overall, estradiol treatment resulted in the down-regulation of 151 genes, including those associated with lipid and nucleotide metabolism. Of particular interest was the up-regulation in estradiol-supplemented cultures of six genes (omcB, trpB, cydA, cydB, pyk and yggV), which suggest a stress response similar to that reported previously in other models of chlamydial persistence. We also observed morphological changes consistent with a persistence response. By comparison, progesterone supplementation resulted in a general up-regulation of an energy utilising response.CONCLUSION:Our data shows for the first time, that the treatment of chlamydial host cells with key reproductive hormones such as progesterone and estradiol, results in significantly altered chlamydial gene expression profiles. It is likely that these chlamydial expression patterns are survival responses, evolved by the pathogen to enable it to overcome the host's innate immune response. The induction of chlamydial persistence is probably a key component of this survival response.

Stop whining and make the best of it: a cross-national comparison of response to regional disadvantage in the wine industry

Our cross-national field study of wine entrepreneurship in the “wrong” places provides some redress to the focus of the “regional advantage” literature on places that have already won and on the firms that benefit from “clusters” and other centers of industry advantage. Regional “disadvantage” is at best a shadowy afterthought to this literature. By poking around in these shadows, we help to synthesize and extend the incipient yet burgeoning literature on entrepreneurial “resourcefulness” and we contribute to the developing body of insights and theory pertinent to the numerous but often ignored firms and startups that mostly need to worry about how they will compete at all now if they are ever to have of chance of “winning” in the future. The core of our findings suggests that understandable – though contested – processes of ingenuity underlie entrepreneurial responses to regional disadvantage. Because we study entrepreneurship that from many angles simply does not make sense, we are also able to proffer a novel perspective on entrepreneurial sensemaking.

AtBAG7, an Arabidopsis Bcl-2-associated athanogene, resides in the endoplasmic reticulum and is involved in the unfolded protein response

The Bcl-2-associated athanogene (BAG) family is an evolutionarily conserved, multifunctional group of cochaperones that perform diverse cellular functions ranging from proliferation to growth arrest and cell death in yeast, in mammals, and, as recently observed, in plants. The Arabidopsis genome contains seven homologs of the BAG family, including four with domain organization similar to animal BAGs. In the present study we show that an Arabidopsis BAG, AtBAG7, is a uniquely localized endoplasmic reticulum (ER) BAG that is necessary for the proper maintenance of the unfolded protein response (UPR). AtBAG7was shown to interact directly in vivo with themolecular chaperone, AtBiP2, by bimolecular fluorescence complementation assays, and the interaction was confirmed by yeast two-hybrid assay. Treatment with an inducer of UPR, tunicamycin, resulted in accelerated cell death of AtBAG7-null mutants. Furthermore, AtBAG7 knockouts were sensitive to known ER stress stimuli, heat and cold. In these knockouts heat sensitivity was reverted successfully to the wild-type phenotype with the addition of the chemical chaperone, tauroursodexycholic acid (TUDCA). Real-time PCR of ER stress proteins indicated that the expression of the heat-shock protein, AtBiP3, is selectively up-regulated in AtBAG7-null mutants upon heat and cold stress. Our results reveal an unexpected diversity of the plant's BAG gene family and suggest that AtBAG7 is an essential component of the UPR during heat and cold tolerance, thus confirming the cytoprotective role of plant BAGs.