Regulation of breast cancer cells by hormones and growth factors : effects on proliferation and basement membrane invasiveness

The current understanding of the regulation of breast cancer cell proliferation and invasiveness by hormones and growth factors is reviewed. It has been shown that polypeptide growth factors are involved in hormone-independent breast cancer, and are sometimes oestrogen-regulated in hormone-responsive models. Basement-membrane invasiveness, relating to the metastatic potential of these cells, is also stimulated by oestrogen in hormone-dependent models, elevated in hormone-independent models, and is growth factor sensitive. Further understanding of the differential effects of growth factors on breast cancer cell proliferation and invasiveness should facilitate better therapeutic exploitation of regulation at this level.

Regulation of proliferation, invasion and growth factor synthesis in breast cancer by steroids

Endogenous ovarian estrogens and progestins appear to play a critical role in the development and progression of breast cancer. Local productions of growth factors probably also contribute to malignant proliferation, while production and activation of collagenolytic enzymes may be equally critical for local invasive processes. The current review focusses on characterization of growth factor-receptor systems operant in normal and malignant breast epithelium. In addition, the determinants of local invasion are reviewed: attachment, modality, and proteose secretion. Finally, data are discussed concerning the regulation of both proliferation and invasion by hormones and antihormonal agents in hormone-dependent breast cancer. The results suggest new potential pharmacologic targets to explore to suppress onset and progression of breast cancer.

Построение автоматической навигационной системы малогабаритного беспилотного летательного аппарата многократного применения = Development of automatic navigation management system for small unmanned aerial vehicle

Современный этап развития комплексов автоматического управления и навигации малогабаритными БЛА многократного применения предъявляет высокие требования к автономности, точности и миниатюрности данных систем. Противоречивость требований диктует использование функционального и алгоритмического объединения нескольких разнотипных источников навигационной информации в едином вычислительном процессе на основе методов оптимальной фильтрации. Получили широкое развитие бесплатформенные инерциальные навигационные системы (БИНС) на основе комплексирования данных микромеханических датчиков инерциальной информации и датчиков параметров движения в воздушном потоке с данными спутниковых навигационных систем (СНС). Однако в современных условиях такой подход не в полной мере реализует требования к помехозащищённости, автономности и точности получаемой навигационной информации. Одновременно с этим достигли значительного прогресса навигационные системы, использующие принципы корреляционно экстремальной навигации по оптическим ориентирам и цифровым картам местности. Предлагается схема построения автономной автоматической навигационной системы (АНС) для БЛА многоразового применения на основе объединения алгоритмов БИНС, спутниковой навигационной системы и оптической навигационной системы. The modern stage of automatic control and guidance systems development for small unmanned aerial vehicles (UAV) is determined by advanced requirements for autonomy, accuracy and size of the systems. The contradictory of the requirements dictates novel functional and algorithmic tight coupling of several different onboard sensors into one computational process, which is based on methods of optimal filtering. Nowadays, data fusion of micro-electro mechanical sensors of inertial measurement units, barometric pressure sensors, and signals of global navigation satellite systems (GNSS) receivers is widely used in numerous strap down inertial navigation systems (INS). However, the systems do not fully comply with such requirements as jamming immunity, fault tolerance, autonomy, and accuracy of navigation. At the same time, the significant progress has been recently demonstrated by the navigation systems, which use the correlation extremal principle applied for optical data flow and digital maps. This article proposes a new architecture of automatic navigation management system (ANMS) for small UAV, which combines algorithms of strap down INS, satellite navigation and optical navigation system.

Исследования и испытания алгоритмов автоматической пилотажно-навигационной системы малогабаритного беспилотного летательного аппарата = Research and testing of automatic navigation management system’s algorithms for small unmanned aerial vehicle

В статье представлено развитие принципа построения автоматической пилотажно-навигационной системы (АПНС) для беспилотного летательного аппарата (БЛА). Принцип заключается в синтезе комплексных систем управления БПЛА не только на основе использования алгоритмов БИНС, но и алгоритмов, объединяющих в себе решение задач формирования и отработки сформированной траектории резервированной системой управления и навигации. Приведены результаты аналитического исследования и данные летных экспериментов разработанных алгоритмов АПНС БЛА, обеспечивающих дополнительное резервирование алгоритмов навигации и наделяющих БЛА новым функциональной способностью по выходу в заданную точку пространства с заданной скоростью в заданный момент времени с учетом атмосферных ветровых возмущений. Предложена и испытана методика идентификации параметров воздушной атмосферы: направления и скорости W ветра. Данные летных испытаний полученного решения задачи терминальной навигации демонстрируют устойчивую работу синтезированных алгоритмов управления в различных метеоусловиях. The article presents a progress in principle of development of automatic navigation management system (ANMS) for small unmanned aerial vehicle (UAV). The principle defines a development of integrated control systems for UAV based on tight coupling of strap down inertial navigation system algorithms and algorithms of redundant flight management system to form and control flight trajectory. The results of the research and flight testing of the developed ANMS UAV algorithms are presented. The system demonstrates advanced functional redundancy of UAV guidance. The system enables new UAV capability to perform autonomous multidimensional navigation along waypoints with controlled speed and time of arrival taking into account wind. The paper describes the technique for real-time identification of atmosphere parameters such as wind direction and wind speed. The flight test results demonstrate robustness of the algorithms in diverse meteorological conditions.

Business process management in small business : a case study

Small Businesses account for a significant portion of the Australian business sector. With Business Process Management (BPM) gaining prominence in recent decades as a means of improving business performance, it would seem to only be a matter of time before it gains momentum within the Small Business sector. One may even question why it has not already achieved more traction within the sector. This case study involves a BPM initiative to develop process infrastructure in an establishing Small Business. It explores whether mainstream BPM tools, techniques and technologies can be applied in a Small Business setting. The chapter provides a background to the case organisation, outlines the activities undertaken in the BPM initiative and distils key observations drawn from participation in the initiative and consultation with stakeholders. Based on the case study experiences, a number of implications are identified for further consideration by the BPM discipline as it continues to address the question of how it can become more widely adopted amongst Small Businesses.

A hypothesis test using bias-adjusted AR estimators for classifying time series in small samples

A new test of hypothesis for classifying stationary time series based on the bias-adjusted estimators of the fitted autoregressive model is proposed. It is shown theoretically that the proposed test has desirable properties. Simulation results show that when time series are short, the size and power estimates of the proposed test are reasonably good, and thus this test is reliable in discriminating between short-length time series. As the length of the time series increases, the performance of the proposed test improves, but the benefit of bias-adjustment reduces. The proposed hypothesis test is applied to two real data sets: the annual real GDP per capita of six European countries, and quarterly real GDP per capita of five European countries. The application results demonstrate that the proposed test displays reasonably good performance in classifying relatively short time series.

MicroRNAs targeting mutant K-ras by electrotransfer inhibit human colorectal adenocarcinoma cell growth in vitro and in vivo

Mutations of K-ras have been found in 30-60% of colorectal carcinomas and are believed to be associated with tumor initiation, tumor progression and metastasis formation. Therefore, silencing of mutant K-ras expression has become an attractive therapeutic strategy for colorectal cancer treatment. The aim of our study was to investigate the effect of microRNA (miRNA) molecules directed against K-ras (miRNA-K-ras) on K-ras expression level and the growth of colorectal carcinoma cell line LoVo in vitro and in vivo. In addition, we evaluated electroporation as a gene delivery method for transfection of LoVo cells and tumors with plasmid DNA encoding miRNA-K-ras (pmiRNA-K-ras). Results of our study indicated that miRNAs targeting K-ras efficiently reduced K-ras expression and cell survival after in vitro electrotransfection of LoVo cells with pmiRNA-K-ras. In vivo, electroporation has proven to be a simple and efficient delivery method for local administration of pmiRNA-K-ras molecules into LoVo tumors. This therapy shows pronounced antitumor effectiveness and has no side effects. The obtained results demonstrate that electrogene therapy with miRNA-K-ras molecules can be potential therapeutic strategy for treatment of colorectal cancers harboring K-ras mutations. © 2010 Nature Publishing Group All rights reserved.

Assessing the role of spatial correlations during collective cell spreading

Spreading cell fronts are essential features of development, repair and disease processes. Many mathematical models used to describe the motion of cell fronts, such as Fisher’s equation, invoke a mean–field assumption which implies that there is no spatial structure, such as cell clustering, present. Here, we examine the presence of spatial structure using a combination of in vitro circular barrier assays, discrete random walk simulations and pair correlation functions. In particular, we analyse discrete simulation data using pair correlation functions to show that spatial structure can form in a spreading population of cells either through sufficiently strong cell–to–cell adhesion or sufficiently rapid cell proliferation. We analyse images from a circular barrier assay describing the spreading of a population of MM127 melanoma cells using the same pair correlation functions. Our results indicate that the spreading melanoma cell populations remain very close to spatially uniform, suggesting that the strength of cell–to–cell adhesion and the rate of cell proliferation are both sufficiently small so as not to induce any spatial patterning in the spreading populations.

JK1 (FAM134B) represses cell migration in colon cancer : a functional study of a novel gene

Background JK1 is a novel cancer-related gene with unknown functional role in carcinogenesis. The aim of this study is to investigate the role of JK1 gene in carcinogenesis in an in vitro cell proliferation and migration analysis model. Methods Small hairpin RNAs (shRNA) were designed to knock-down JK1 expression in colon cancer cell line (SW480) using transduction ready lentiviral particles. Cell proliferation and cell migration assays were performed on multiple extracellular matrices to investigate the cellular effects of JK1 in colon cancer cells. A non-cancer colonic epithelial cell line (FHC) was used to compare the expression of JK1 in cancer cell line. Results JK1 knock-down did not affect cellular proliferation or survival in colon cancer. However, the manipulation increased cancer cell migration rates on collagen and fibronectin substrates. Conclusions JK1 was shown for the first time to have a functional role in the pathogenesis of colon cancer. The results imply that JK1 represses the capacity of cancer cells to migrate within their tissue. They also concurred with the previous findings of JK1 activity correlations with clinical and pathological features in colon cancer. The capacity may have utility as a means to prevent cancer cells forming metastases.

Measurement of small ions near a busy motorway

Combustion sources are well-known sources of electrical ions (Howard, J.B. et al. 1973). Motor vehicles emissions are one of the main sources of ions in urban environments. The presence of charged particles in motor vehicle emissions has been known for many years (Kittelson, 1986; Yu et al, 2004; Jung and Kittelson, 2005). Although these particles are probably charged by the attachment of air ions, there is very little information on the nature, sign and magnitude of the small ions (diameter < 1.6 nm) emitted by motor vehicles and/or present by the sides of roads.

Determining gas sampling timelines for estimating emissions in small chamber incubation experiments

A laboratory experiment was set up in small chambers for monitoring greenhouse gas emissions and determining the most suitable time for sampling. A six-treatment experiment was conducted, including a one week pre-incubation and a week for incubation. Timelines for sampling were 1, 2, 3, 6 and 24 hours after closing the lid of the incubation chambers. Variation in greenhouse gas fluxes was high due to the time of sampling. The rates of gas emissions increased in first three hours and decreased afterward. The rates of greenhouse gas emissions at 3 hours after closing lids was close to the mean for the 24-h period.

Genome-wide analysis in a murine Dnmt1 knockdown model identifies epigenetically silenced genes in primary human pituitary tumors

DNA methylation at promoter CpG islands (CGI) is an epigenetic modification associated with inappropriate gene silencing in multiple tumor types. In the absence of a human pituitary tumor cell line, small interfering RNA-mediated knockdown of the maintenance methyltransferase DNA methyltransferase (cytosine 5)-1 (Dnmt1) was used in the murine pituitary adenoma cell line AtT-20. Sustained knockdown induced reexpression of the fully methylated and normally imprinted gene neuronatin (Nnat) in a time-dependent manner. Combined bisulfite restriction analysis (COBRA) revealed that reexpression of Nnat was associated with partial CGI demethylation, which was also observed at the H19 differentially methylated region. Subsequent genome-wide microarray analysis identified 91 genes that were significantly differentially expressed in Dnmt1 knockdown cells (10% false discovery rate). The analysis showed that genes associated with the induction of apoptosis, signal transduction, and developmental processes were significantly overrepresented in this list (P < 0.05). Following validation by reverse transcription-PCR and detection of inappropriate CGI methylation by COBRA, four genes (ICAM1, NNAT, RUNX1, and S100A10) were analyzed in primary human pituitary tumors, each displaying significantly reduced mRNA levels relative to normal pituitary (P < 0.05). For two of these genes, NNAT and S100A10, decreased expression was associated with increased promoter CGI methylation. Induced expression of Nnat in stable transfected AtT-20 cells inhibited cell proliferation. To our knowledge, this is the first report of array-based "epigenetic unmasking" in combination with Dnmt1 knockdown and reveals the potential of this strategy toward identifying genes silenced by epigenetic mechanisms across species boundaries.

A benzothiadiazole end capped donor–acceptor based small molecule for organic electronics

A benzothiadiazole end-capped small molecule 3,6-bis(5-(benzo[c][1,2,5] thiadiazol-4-yl)thiophen-2-yl)-2,5-bis(2-butyloctyl)pyrrolo[3,4-c]pyrrole-1, 4(2H,5H)-dione (BO-DPP-BTZ) using a fused aromatic moiety DPP (at the centre) is designed and synthesized. BO-DPP-BTZ is a donor-acceptor-donor (D-A-D) structure which possesses a band gap of 1.6 eV and exhibits a strong solid state ordering inferred from ∼120 nm red shift of the absorption maxima from solution to thin film. Field-effect transistors utilizing a spin coated thin film of BO-DPP-BTZ as an active layer exhibited a hole mobility of 0.06 cm 2 V-1 s-1. Solution-processed bulk heterojunction organic photovoltaics employing a blend of BO-DPP-BTZ and [70]PCBM demonstrated a power conversion efficiency of 0.9%.

Small firms and the challenge of equality, diversity and difference

Purpose The purpose of this paper is to introduce the papers contributing to this special issue and to locate them within the broader questions about the role of small firms in enabling or alleviating issues of equality, diversity, and difference for various groups in society. Design/methodology/approach The literature dealing with the issues of equality, diversity, and difference pertaining to the operation of and/or working in smaller firms was reviewed prior to drawing out the key points from the submitted papers and considering the contribution they make to this literature. Findings Overall, one's these five papers contribute to one's understanding of the issues facing those in business or self‐employment, working in small business or wanting to pursue enterprise. Originality/value Rarely are questions asked about the assumed role small firms play in mitigating social exclusion for a range of groups in society. By addressing questions which explore the challenge of equality, diversity, and difference for small business in their establishment, management, and effective operation using interdisciplinary frameworks and different methodologies, a better understanding of the role of small business in society can be developed.