Epidermal growth factor-induced ovarian carcinoma cell migration is associated with JAK2/STAT3 signals and changes in the abundance and localization of α6β1 integrin

Peritoneal dissemination of ovarian carcinoma is mediated by epithelial–mesenchymal interconversions leading to the disruption of cell–cell contact and modulation of cell–extracellular matrix (ECM) interactions. The present study was designed to evaluate the effects of epidermal growth factor (EGF) as a modulator of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) signalling and changes in integrin expression during the process similar to EMT. A fibroblastic morphology with reduced intercellular cell contacts and increased cell motility was observed in ovarian cancer cell lines in response to EGF and was concomitant with the up regulation of EMT-associated N-cadherin and vimentin expression. These changes were accompanied by an increase in α2, α6 and β1 integrin subunits and activation of JAK2 and STAT3 signalling which was suppressed by a specific JAK2 inhibitor. Consistent with the suppression of STAT3 activity, N-cadherin and vimentin expression were abrogated and was coherent with the loss of cell motility and the expression of α6 and β1 integrin subunits. Neutralizing antibodies against α6 and β1 subunits inhibited cancer cell migration. A strong correlation between the expression of N-cadherin, vimentin and JAK2/STAT3 levels were detected in high-grade ovarian tumors and was consistent with the previously reported enhanced expression of α6 integrin subunit in advanced tumors [Ahmed N, Riley C, Oliva K, Rice G, Quinn M. Ascites induces modulation of α6β1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma. British Journal of Cancer 2005;92:1475–85]. Our data incorporating the clinical samples and the cancer cell lines is the first to demonstrate that JAK2/STAT3 pathway may be one of the downstream events in EMT-like process and α6β1 integrin-mediated signalling in ovarian carcinomas.

Role of exercise in the development of bone strength during growth

Exercise during growth may increase peak bone mass; if the benefits are maintained it may reduce the risk of fracture later in life (1). It is hypothesised that exercise will preferentially enhance bone formation on the surface of cortical bone that is undergoing bone modeling at the time (2). Therefore, exercise may increase bone mass accrual on the outer periosteal surface during the pre- and peri-pubertal years, and on the inner endocortical surface during puberty (3). An increase in bone formation on the periosteal surface is, however, more effective for increasing bone strength than medullary contraction (4). While exercise may have a role in osteoporosis prevention, there is little evidential basis to support this notion. It is generally accepted that weight-bearing exercise is important, but it is not known how much, how often, what magnitude or how long children need to exercise before a clinically important increase in bone density is obtained. In this thesis, the effect of exercise on the growing skeleton is investigated in two projects. The first quantifies the magnitude and number of loads associated with and in a moderate and low impact exercise program and non-structured play. The second project examines how exercise affects bone size and shape during different stages of growth. Study One: The Assessment of the Magnitude of Exercise Loading and the Skeletal Response in Girls Questions: 1) Does moderate impact exercise lead to a greater increase in BMC than low impact exercise? 2) Does loading history influence the osteogenic response to moderate impact exercise? 3) What is the magnitude and number of loads that are associated with a moderate and low impact exercise program? Methods: Sixty-eight pre-and early-pubertal girls (aged 8.9±0.2 years) were randomised to either a moderate or low impact exercise regime for 8.5-months. In each exercise group the girls received either calcium fortified (-2000 mg/week) or non-fortified foods for the duration of the study. The magnitude and number of loads associated with the exercise programs and non-structured play were assessed using a Pedar in-sole mobile system and video footage, respectively. Findings: After adjusting for baseline BMC, change in length and calcium intake, the girls in the moderate exercise intervention showed greater increases in BMC at the tibia (2.7%) and total body (1.3%) (p ≤0.05). Girl's who participated in moderate impact sports outside of school, showed greater gains in BMC in response to the moderate impact exercise program compared to the low impact exercise program (2.5 to 4.5%, p ≤0.06 to 0.01). The moderate exercise program included -400 impacts per class, that were applied in a dynamic manner and the magnitude of impact was up to 4 times body weight. Conclusion: Moderate-impact exercise may be sufficient to enhance BMC accrual during the pre-pubertal years. However, loading history is likely to influence the osteogenic response to additional moderate impact exercise. These findings contribute towards the development of school-based exercise programs aimed at improving bone health of children. Study Two: Exercise Effect on Cortical Bone Morphology During Different Stages of Maturation in Tennis Players Questions: 1) How does exercise affect bone mass (BMC) bone geometry and bone strength during different stages of growth? 2) Is there an optimal stage during growth when exercise has the greatest affect on bone strength? Methods: MRI was used to measure average total bone, cortical and medullary areas at the mid- and distal-regions of the playing and non-playing humerii in 47 pre-, peri- and post-pubertal competitive female tennis players aged 8 to 17 years. To assess bone rigidity, each image was imported into Scion Image 4.0.2 and the maximum, minimum and polar second moments of area were calculated using a custom macro. DXA was used to measure BMC of the whole humerus. Longitudinal data was collected on 37 of the original cohort. Findings: Analysis of the entire cohort showed that exercise was associated with increased BMC and cortical area (8 to 14%), and bone rigidity (11 to 23%) (all p ≤0.05). The increase in cortical bone area was associated with periosteal expansion in the pre-pubertal years and endocortical contraction in the post-pubertal years (p ≤0.05). The exercise-related gains in bone mass that were accrued at the periosteum during the pre-pubertal years, did not increase with advanced maturation and/or additional training. Conclusion: Exercise increased cortical BMC by enhancing bone formation on the periosteal surface during the pre-pubertal years and on the endocortical surface in the post-pubertal years. However, bone strength only increased in response to bone acquisition on the periosteal surface. Therefore the pre-pubertal years appear to be the most opportune time for exercise to enhance BMC accrual and bone strength

Teacher professional growth : a study of primary teachers involved in mathematics professional development

The overall purpose of this study was to examine whether professional development programs can act as appropriate vehicles for the professional growth of teachers of primary mathematics. A longitudinal study was conducted of primary teachers involved in a Victorian mathematics professional development program — Exploring Mathematics In Classrooms (EMIC). The professional growth of six teacher participants in one EMIC course was examined over a period of 18 months. The teachers selected were from four different schools located in the southern metropolitan region of Melbourne. The central interest of this study was in teacher professional growth and accordingly the perspective sought was predominantly that of the teacher. A case study research approach was adopted and data were gathered through observations, interviews, questionnaire, and the collection of teacher work documents. A theoretical model of teacher professional growth was used to represent the teachers' growth. The study generated data on the nature of teacher professional growth and the features of professional development programs likely to influence teacher professional growth. All of the teachers reported and demonstrated growth with respect to their mathematics teaching, in areas associated with their: Classroom Practice, Knowledge and Beliefs, and Professional Attributes. The teachers' growth was highly individualistic, with no two teachers demonstrating exactly the same professional growth outcomes, or the same growth processes. The data provided evidence to confirm that teacher growth is a complex and gradual learning process. For each of the teachers several different routes to change and growth were evident, drawing attention to the non-linear nature of growth. The teachers' responses to the professional development program were influenced by various contextual and personal factors. The data provided evidence of a strong link between the content and outcomes of professional development programs — the outcomes reported and demonstrated by the teachers reflected the content of the EMIC program. Key factors associated with mathematics professional development programs perceived as influencing growth were: program content; program structure; and program presentation. A significant finding was the strong influence on teacher growth of the presenters of professional development programs—some data suggested that the 'quality' of the program presenter is fundamental to the success of any professional development program. The study provided insight into the processes involved in teacher professional growth and factors associated with the way in which professional development programs influence growth. The theoretical model of teacher professional growth used in this study has been elaborated and recommendations which might inform the design and implementation of future professional development programs have been made.

Effects of survivin antagonists of growth of established tumors and B7-1 immunogene therapy

Background: Survivin, a member of the inhibitor of apoptosis (IAP) protein family, is detectable in most types of cancer, and its presence is associated with a poor prognosis. We determined the effects of gene-based therapies that inhibit survivin function in a mouse tumor model. Methods: Using five to six mice per treatment group, we injected tumors derived from mouse EL-4 thymic lymphoma cells with plasmids encoding antisense survivin, a dominant-negative mutant survivin, and the T-cell costimulator B7-1. Expression of endogenous survivin and the proteins encoded by the injected plasmids were examined by immunohistochemical staining of tumor sections and by western blot and flow cytometry analyses of isolated tumor cells. Tumor growth, the generation of antitumor cytotoxic T-lymphocyte (CTL) activity, apoptosis, and the contribution of leukocyte subsets to antitumor activity were measured. All statistical tests were two-sided. Results: Large (1.0-cm diameter) tumors had approximately 10-fold more survivin than small (0.2-cm diameter) tumors. At 28 days after injection, antisense and dominant-negative mutant survivin plasmids statistically significantly inhibited the growth of both small (P = .006 and P = .0018, respectively) and large (P<.001 for both plasmids) EL-4 tumors compared with tumors injected with empty plasmid. The growth of large tumors was further inhibited by intratumoral injection with antisense survivin and B7-1 (P = .004); thus, inhibition of survivin expression renders large tumors susceptible to B7-1-mediated immunotherapy. Mice whose tumors were completely eradicated by injection of B7-1 remained tumor free for 26 days after re-injection with EL-4 cells (when the experiment ended). Compared with tumors injected with empty plasmid, tumors injected with survivin-based plasmids had increased apoptosis, and animals bearing such tumors generated more antitumor CTLs. Conclusion: Intratumoral injection of plasmids that block survivin expression and stimulate the generation of tumor-specific CTLs may be beneficial for the treatment of large lymphomas.

Achieving growth in the Pacific islands : an introduction

The Small Island Developing States (SIDS)1 in the Pacific, spread out over an area of 30 million square kilometres of ocean, and home to over 9 million people, face a complex and unique set of development challenges. As small, highly open economies they are particularly susceptible to external shocks, including fluctuations in import prices and export earnings in particular. Remoteness from major ports and export markets, low levels of connectivity with the outside world and susceptibility to natural hazards further complicate matters and have resulted in the Pacific islands being amongst the most vulnerable economies in the world. In spite of their increasing integration into global markets, most face further challenges owing to very limited absorptive capacities, limited resources, inadequate technology, lack of infrastructure and poor economic management and institutional capabilities. As a consequence, economic growth and related outcomes in most remain heavily reliant on external resources, typically including at least one of aid, migrant remittances, and foreign direct investment (FDI) (AusAID 2008 and McGillivray et al. 2008). The particular constraints and growth challenges of Pacific SIDS are too often overlooked in the development research literature. Moreover, the policy debate on how to promote and achieve growth in the Pacific islands can benefit from a deeper understanding of the nature and consequences of these often unique, combination of constraints. This Focus is devoted to development challenges facing these islands, specifically relating to the achievement of economic growth, and draws on five papers that were presented or tabled at the World Institute for Development Economics Research (WIDER) ‘Fragility and Development’ research project meeting held in Fiji in December 2006.

Measuring public infrastructure construction impacts on economic growth

The results identify the long-run equilibrium relationships among economic variables in Australia. This study can provide policy makers with information on a one standard error shock to each variable and insights into what percentages of the forecast error variance of a variable are explained by the innovations of each variable.

Growth restriction before and after birth increases kinase signaling pathways in the adult rat heart

To investigate the mechanisms for the previously reported development of adult cardiac hypertrophy in male rats following growth restriction, the levels of oxidative stress and activation of signaling kinases were measured in the left ventricle (LV) of adult rat offspring. In experiment one, bilateral uterine vessel ligation to induce uteroplacental insufficiency and growth restriction in the offspring (Restricted) or sham surgery was performed during pregnancy. Litters from sham mothers had litter size either reduced (Reduced Litter), which also restricted postnatal growth, or were left unaltered (Control). In males, Reduced Litter offspring had increased LV phosphorylation of AMPKa, p38 MAPK and Akt compared with Restricted and Controls (P,0.05). In females, both Restricted and Reduced Litter adult offspring had increased LV phosphorylation of p38 MAPK and Akt, however, only Restricted offspring had increased phosphorylation of AMPKa (P,0.05). In addition, only Restricted male offspring displayed LV oxidative stress (P,0.05). Experiment two investigated in mothers exposed to uteroplacental insufficiency or sham surgery the effects of cross-fostering offspring at birth, and therefore the effects of the postnatal lactational environment. Surprisingly, the cross-fostering itself resulted in increased LV phosphorylation of AMPKa and Akt in females and increased phosphorylation of Akt in males compared with Control non-cross-fostered offspring (P,0.05). In conclusion, kinase signaling in the adult LV can be programmed by uteroplacental insufficiency induced growth restriction in a gender-specific manner. In addition, the heart of adult rats is also sensitive to programming following the postnatal intervention of cross-fostering alone as well as by postnatal growth restriction.

Medical image retrieval with query-dependent feature fusion based on one-class SVM

Due to the huge growth of the World Wide Web, medical images are now available in large numbers in online repositories, and there exists the need to retrieval the images through automatically extracting visual information of the medical images, which is commonly known as content-based image retrieval (CBIR). Since each feature extracted from images just characterizes certain aspect of image content, multiple features are necessarily employed to improve the retrieval performance. Meanwhile, experiments demonstrate that a special feature is not equally important for different image queries. Most of existed feature fusion methods for image retrieval only utilize query independent feature fusion or rely on explicit user weighting. In this paper, we present a novel query dependent feature fusion method for medical image retrieval based on one class support vector machine. Having considered that a special feature is not equally important for different image queries, the proposed query dependent feature fusion method can learn different feature fusion models for different image queries only based on multiply image samples provided by the user, and the learned feature fusion models can reflect the different importances of a special feature for different image queries. The experimental results on the IRMA medical image collection demonstrate that the proposed method can improve the retrieval performance effectively and can outperform existed feature fusion methods for image retrieval.

Transcriptional profiling of growth perturbations of the human malaria parasite Plasmodium falciparum

Functions have yet to be defined for the majority of genes of Plasmodium falciparum, the agent responsible for the most serious form of human malaria. Here we report changes in P. falciparum gene expression induced by 20 compounds that inhibit growth of the schizont stage of the intraerythrocytic development cycle. In contrast with previous studies, which reported only minimal changes in response to chemically induced perturbations of P. falciparum growth, we find that ~59% of its coding genes display over three-fold changes in expression in response to at least one of the chemicals we tested. We use this compendium for guilt-by-association prediction of protein function using an interaction network constructed from gene co-expression, sequence homology, domain-domain and yeast two-hybrid data. The subcellular localizations of 31 of 42 proteins linked with merozoite invasion is consistent with their role in this process, a key target for malaria control. Our network may facilitate identification of novel antimalarial drugs and vaccines.

Simulating urban growth in a developing nation's region using a cellular automata-based model

Urbanization is one of the most evident global changes. Research in the field of urban growth modelling has generated models that explore for drivers and components of the urban growth dynamics. Cellular automata (CA) modeling is one of the recent advances, and a number of CA-based models of urban growth have produced satisfactory simulations of spatial urban expansion over time. Most application and test of CA-based models of urban growth which provide likely and reliable simulations has been developed in urban regions of developed nations; urban regions in the United States, in particular. This is because most of the models were developed in universities and research centers of developed nations, and these regions have the required data, which is extensive. Most of the population growth in the world, however, occurs in the developing world. While some European countries show signs of stabilization of their population, in less developed countries, such as India, population still grows exponentially. And this growth is normally uncoordinated, which results in serious environmental and social problems in urban areas. Therefore, the use of existing dynamic–spatial models of urban growth in regions of developing nations could be a means to assist planners and decision makers of these regions to understand and simulate the process of urban growth and test the results of different development strategies. The pattern of growth of urban regions of developing nations, however, seems to be different of the pattern of developed countries. The former use to be more dense and centralized, normally expanding outwards from consolidated urban areas; while the second is normally more fragmented and sparse. The present paper aims to investigate to how extent existing CA-based urban growth models tested in developed nations can also be applied to a developing country urban area. The urban growth model was applied to Porto Alegre City, Brazil. An expected contiguous expansion from existing urban areas has been obtained as following the historical trends of growth of the region. Moreover, the model was sensitive and able to portray different pattern of growth in the study area by changing the value of its parameters.

Predictors and responses to the growth in physical violence during adolescence : a comparison of students in Washington State and Victoria, Australia

This study investigates patterns in violence over 3 time points in early to midadolescence in 2 statewide representative samples of youth, one in Washington State, USA, and the other in Victoria, Australia. Comparable data collection methods in both states were used to cross-nationally compare patterns of violence, risk factors, and responses to violence (school suspensions and arrests) in 2 policy contexts. Risk factors include early use of alcohol, binge drinking, involvement with antisocial peers, family conflict, poor family management, sensation seeking, and bully victimization. These are modeled as correlates of initial violence and predictors of change in violence over a 3-year period, from ages 12–15, for participating youth. Results suggest that patterns and predictors of violence are mostly similar in the 2 states. Initial levels of violence (age 13) and change over time in violence were associated in both states with more youth school suspensions and more police arrests in Grade 9. Some cross-national differences were also shown. For example, correlations of violence with gender and violence with binge drinking were stronger in Victoria, whereas correlations of violence with early use of alcohol and with antisocial peer involvement were stronger in Washington State. Antisocial peer involvement and family conflict were significant predictors of a gradual increase in violence from Grades 7–9 for youth in Victoria only. Implications are discussed with attention to prevention and intervention efforts.

Microphone identification using one-class classification approach

Rapid growth of technical developments has created huge challenges for microphone forensics - a subcategory of audio forensic science, because of the availability of numerous digital recording devices and massive amount of recording data. Demand for fast and efficient methods to assure integrity and authenticity of information is becoming more and more important in criminal investigation nowadays. Machine learning has emerged as an important technique to support audio analysis processes of microphone forensic practitioners. However, its application to real life situations using supervised learning is still facing great challenges due to expensiveness in collecting data and updating system. In this paper, we introduce a new machine learning approach which is called One-class Classification (OCC) to be applied to microphone forensics; we demonstrate its capability on a corpus of audio samples collected from several microphones. Research results and analysis indicate that OCC has the potential to benefit microphone forensic practitioners in developing new tools and techniques for effective and efficient analysis.

Identifying microphone from noisy recordings by using representative instance one class-classification approach

Rapid growth of technical developments has created huge challenges for microphone forensics - a sub-category of audio forensic science, because of the availability of numerous digital recording devices and massive amount of recording data. Demand for fast and efficient methods to assure integrity and authenticity of information is becoming more and more important in criminal investigation nowadays. Machine learning has emerged as an important technique to support audio analysis processes of microphone forensic practitioners. However, its application to real life situations using supervised learning is still facing great challenges due to expensiveness in collecting data and updating system. In this paper, we introduce a new machine learning approach which is called One-class Classification (OCC) to be applied to microphone forensics; we demonstrate its capability on a corpus of audio samples collected from several microphones. In addition, we propose a representative instance classification framework (RICF) that can effectively improve performance of OCC algorithms for recording signal with noise. Experiment results and analysis indicate that OCC has the potential to benefit microphone forensic practitioners in developing new tools and techniques for effective and efficient analysis.

One-Step synthesis of the pine-shaped nanostructure of aluminum nitride and its photoluminescence properties

An array of pine-shaped nanostructures of aluminum nitride (AlN) was synthesized through direct reaction between Al vapor and nitrogen gas in direct current (DC) arc discharge plasma without any catalyst or template. The as-prepared nanostructure consists of many pine-needle-shaped leaves with conical shape tips. The structure, morphology, and optical property of the nanostructure have been characterized by X-ray powder diffraction, energy-dispersive X-ray spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy, Raman spectroscopy, and photoluminescence. A possible growth mechanism of the pine-shaped nanostructure was discussed. Two factors were found to be essential for branched nanostructure growth, i.e., the reaction time and N2 pressure. The photoluminescence spectrum of the nanostructure of AlN revealed an intense emission band, suggesting that there may be potential applications in electronic and optoelectronic nanodevices.

One-step synthesis of AlN branched nanostructures by an improved DC arc discharge plasma method

Aluminium nitride (AlN) branched nanostructures with tree shapes and sea urchin shapes are synthesized via a one-step improved DC arc discharge plasma method without any catalyst and template. The branched nanostructures with tree shapes and sea urchin shapes can be easily controlled by the location of collection. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies show that the branches of tree shaped nanostructures grow in a sequence of nanowires, nanomultipeds and nanocombs. The growth mechanisms of these branched nanostructures are discussed in detail. The optical properties of AlN branched nanostructures with tree shapes and sea urchin shapes are investigated.