High level of MT-MMP expression is associated with invasiveness of cervical cancer cells

MMP-2 (gelatinase A) has been associated with the invasive potential of many cancer cells both in vitro and in vivo. It is now becoming clear that the activation of this enzyme might be a key step in tumor invasion. This activation process has been shown to be a membrane-associated pathway inducible by various agents such as collagen type I, concanavalin A or TGF-β, but its physiological regulation is still largely unresolved. MT-MMP was recently discovered and described as a potential gelatinase-A activator. In the present study, we investigated the expression of MT-MMP (membrane-type metalloproteinase) in cervical cancer cells both in vitro and in vivo. Comparing several in vitro-transformed cervical cell lines, previously shown to display different invasive potentials, our results showed that the ability of cells to overexpress MT-MMP mRNA following ConA induction correlated with their ability to activate gelatinase A and with a highly invasive behavior. Moreover, using immunohistochemistry and in situ hybridization, we found a higher level of MT-MMP expression in invasive cervical carcinoma and lymphnode metastases compared to its expression in non-invasive CIN III lesions. Our in vivo observations also clearly demonstrated a cooperation between stromal and tumor cells for the production of MT-MMP. Taken together, our results clearly correlated high level MT-MMP expression with invasiveness, and thus suggested that MT-MMP might play a crucial role in cervical tumor invasion.

Sertoli cells as paracrine modulators of DNA synthesis in rat peritubular myoid cells in culture

To determine whether Sertoli cells influence DNA synthesis by rat peritubular myoid cells in vitro, the effects of Sertoli cells on [3H]thymidine incorporation by peritubular myoid cells in a coculture situation were examined. Incubation of testicular peritubular myoid cells with Sertoli cells in coculture induced a significant increase in [3H]thymidine incorporation by peritubular myoid cells. This indicates a cell-cell cooperation between Sertoli and peritubular myoid cells in the testis in terms of DNA synthesis. Secreted factors from Sertoli cells, as tested in a parabiotic culture situation, also increased [3H]thymidine incorporation by peritubular myoid cells. Moreover, in terms of total cellular protein, cocultures of Sertoli cells and peritubular myoid cells resulted in a significant increase when compared with the monocultures, and this coculture effect substituted for the stimulatory response of serum on peritubular myoid cell monoculture. This study investigated the cooperative role of Sertoli cells and peritubular myoid cells in paracrine regulation of testicular functions.

Very high resolution optical satellites for DEM generation : a review

The advent of very high resolution (VHR) optical satellites capable of producing stereo images led to a new era in extracting digital elevation model which commenced with the launch of IKONOS. The special specifications of VHR optical satellites besides, the significant economic profit stimulated other countries and companies to have their constellations such as EROS-A1 and EROS-B1 as the cooperation between Israel and ImageSat. QuickBird, WorldView-1 and WorldVew-2 were launched by DigitalGlobe. ALOS and GeoEye-1 were offered by Japan and GeoEye Respectively. In addition to aforementioned satellites, Indian and South Korea initiated their own constellation by launching CartoSat-1 and KOPOSAT-2 respectively.The availability of all so-called satellites make a huge market of stereo images for extracting of digital elevation model and other correspondent applications such as, producing orthorectifcatin images and updating maps. Therefore, there is a need for a comprehensive comparison for scientific and commercial clients to choose appropriate satellite images and methods of generating digital elevation model to obtain optimum results. This paper will thus give a review about the specifications of VHR optical satellites. Then it will discuss the automatic elaborating of digital elevation model. Finally an overview of studies and corresponding results is reported.

Beyond the Producer/Consumer Divide : Key Principles of Produsage and Opportunities for Innovation

Though popular, concepts such as Toffler's 'prosumer' (1970; 1980; 1990) are inherently limited in their ability to accurately describe the makeup and dynamics of current co-creative environments, from fundamentally non-profit initiatives like the Wikipedia to user-industry partnerships that engage in crowdsourcing and the development of collective intelligence. Instead, the success or failure of such projects can be understood best if the traditional producer/consumer divide is dissolved, allowing for the emergence of the produser (Bruns, 2008). A close investigation of leading spaces for produsage makes it possible to extract the key principles which underpin and guide such content co-creation, and to identify how innovative pro-am partnerships between commercial entities and user communities might be structured in order to maximise the benefits that both sides will be able to draw from such collaboration. This chapter will outline these principles, and point to successes and failures in applying them to pro- am initiatives.

Multi-objective models and techniques for analysing the absolute capacity of railway networks

Railway capacity determination and expansion are very important topics. In prior research, the competition between different entities such as train services and train types, on different network corridors however have been ignored, poorly modelled, or else assumed to be static. In response, a comprehensive set of multi-objective models have been formulated in this article to perform a trade-off analysis. These models determine the total absolute capacity of railway networks as the most equitable solution according to a clearly defined set of competing objectives. The models also perform a sensitivity analysis of capacity with respect to those competing objectives. The models have been extensively tested on a case study and their significant worth is shown. The models were solved using a variety of techniques however an adaptive E constraint method was shown to be most superior. In order to identify only the best solution, a Simulated Annealing meta-heuristic was implemented and tested. However a linearization technique based upon separable programming was also developed and shown to be superior in terms of solution quality but far less in terms of computational time.

Firms’ information system characteristics and management accounting adaptability

This study explores the relationship between the qualities of an information system and management accounting adaptability (MAA) and effectiveness in firms. Design/methodology/approach I develop and empirically test a model where the qualities of the information system and management accounting effectiveness are mediated by MAA. Findings Information system flexibility (ISF) and shared knowledge had a significant and positive correlation with MAA, which in turn had a positive and significant correlation with management accounting effectiveness. There was also a moderation effect of ISF on the correlation betweeen information system integration and MAA. Research implications Information system integration may not lead to management accounting stability, but the lack of flexibility of a system and a lack of cooperation between the stakeholders might lead to its stagnation. Practical implications Organizations are advised to implement solutions that are relatively flexible and modular, as well as encourage cooperation between stakeholders to fully leverage and improve the existing and future systems. Originality/value The study extends the discourse on the interaction between management accounting and information systems by exploring the role of a number of factors that drive MAA.

Energy-Efficient Decentralized Cooperative Routing in Wireless Networks

Wireless adhoc networks transmit information from a source to a destination via multiple hops in order to save energy and, thus, increase the lifetime of battery-operated nodes. The energy savings can be especially significant in cooperative transmission schemes, where several nodes cooperate during one hop to forward the information to the next node along a route to the destination. Finding the best multi-hop transmission policy in such a network which determines nodes that are involved in each hop, is a very important problem, but also a very difficult one especially when the physical wireless channel behavior is to be accounted for and exploited. We model the above optimization problem for randomly fading channels as a decentralized control problem - the channel observations available at each node define the information structure, while the control policy is defined by the power and phase of the signal transmitted by each node. In particular, we consider the problem of computing an energy-optimal cooperative transmission scheme in a wireless network for two different channel fading models: (i) slow fading channels, where the channel gains of the links remain the same for a large number of transmissions, and (ii) fast fading channels, where the channel gains of the links change quickly from one transmission to another. For slow fading, we consider a factored class of policies (corresponding to local cooperation between nodes), and show that the computation of an optimal policy in this class is equivalent to a shortest path computation on an induced graph, whose edge costs can be computed in a decentralized manner using only locally available channel state information (CSI). For fast fading, both CSI acquisition and data transmission consume energy. Hence, we need to jointly optimize over both these; we cast this optimization problem as a large stochastic optimization problem. We then jointly optimize over a set of CSI functions of the local channel states, and a c- - orresponding factored class of control poli.

Across the Oceans : Development of Overseas Business Information Transmission, 1815-1875

Earlier studies have shown that the speed of information transmission developed radically during the 19th century. The fast development was mainly due to the change from sailing ships and horse-driven coaches to steamers and railways, as well as the telegraph. Speed of information transmission has normally been measured by calculating the duration between writing and receiving a letter, or between an important event and the time when the news was published elsewhere. As overseas mail was generally carried by ships, the history of communications and maritime history are closely related. This study also brings a postal historical aspect to the academic discussion. Additionally, there is another new aspect included. In business enterprises, information flows generally consisted of multiple transactions. Although fast one-way information was often crucial, e.g. news of a changing market situation, at least equally important was that there was a possibility to react rapidly. To examine the development of business information transmission, the duration of mail transport has been measured by a systematic and commensurable method, using consecutive information circles per year as the principal tool for measurement. The study covers a period of six decades, several of the world's most important trade routes and different mail-carrying systems operated by merchant ships, sailing packets and several nations' steamship services. The main sources have been the sailing data of mail-carrying ships and correspondence of several merchant houses in England. As the world's main trade routes had their specific historical backgrounds with different businesses, interests and needs, the systems for information transmission did not develop similarly or simultaneously. It was a process lasting several decades, initiated by the idea of organizing sailings in a regular line system. The evolution proceeded generally as follows: originally there was a more or less irregular system, then a regular system and finally a more frequent regular system of mail services. The trend was from sail to steam, but both these means of communication improved following the same scheme. Faster sailings alone did not radically improve the number of consecutive information circles per year, if the communication was not frequent enough. Neither did improved frequency advance the information circulation if the trip was very long or if the sailings were overlapping instead of complementing each other. The speed of information transmission could be improved by speeding up the voyage itself (technological improvements, minimizing the waiting time at ports of call, etc.) but especially by organizing sailings so that the recipients had the possibility to reply to arriving mails without unnecessary delay. It took two to three decades before the mail-carrying shipping companies were able to organize their sailings in an optimal way. Strategic shortcuts over isthmuses (e.g. Panama, Suez) together with the cooperation between steamships and railways enabled the most effective improvements in global communications before the introduction of the telegraph.

Land condition monitoring information for reef catchments: a new era

Land condition monitoring information is required for the strategic management of grazing land and for a better understanding of ecosystem processes. Yet, for policy makers and those land managers whose properties are situated within north-eastern Australia's vast Great Barrier Reef catchments, there has been a general lack of geospatial land condition monitoring information. This paper provides an overview of integrated land monitoring activity in rangeland areas of two major Reef catchments in Queensland: the Burdekin and Fitzroy regions. The project aims were to assemble land condition monitoring datasets that would assist grazing land management and support decision-makers investing public funds; and deliver these data to natural resource management(NRM) community groups, which had been given increased responsibility for delivering local environmental outcomes. We describe the rationale and processes used to produce new land condition monitoring datasets derived from remotely sensed Landsat thematic mapper (TM) and high resolution SPOT 5 satellite imagery and from rapid land condition ground assessment. Specific products include subcatchment groundcover change maps, regional mapping of indicative very poor land condition, and stratified land condition site summaries. Their application, integration, and limitations are discussed. The major innovation is a better understanding of NRM issues with respect to land condition across vast regional areas, and the effective transfer of decision-making capacity to the local level. Likewise, with an increased ability to address policy questions from an evidence-based position, combined with increased cooperation between community, industry and all levels of government, a new era has emerged for decision-makers in rangeland management.

A review of Australian classical biological control of weeds programs and research activities over the past 12 years

Considerable progress has been made towards the successful classical biological control of many of Australia’s exotic weeds over the past decade. Some 43 new arthropod or pathogen agents were released in 19 projects. Effective biological control was achieved in several projects with the outstanding successes being the control of rubber vine, Cryptostegia grandiflora, and bridal creeper, Asparagus asparagoides. Significant developments also occurred in target prioritization, procedures for target and agent approval, funding, infrastructure and cooperation between agencies. Scientific developments included greater emphasis on climate matching, plant and agent phylogeny, molecular diagnostics, agent prioritization and agent evaluation.

Deriving artefact-centric interfaces for overloaded web services

We present a novel framework and algorithms for the analysis of Web service interfaces to improve the efficiency of application integration in wide-spanning business networks. Our approach addresses the notorious issue of large and overloaded operational signatures, which are becoming increasingly prevalent on the Internet and being opened up for third-party service aggregation. Extending upon existing techniques used to refactor service interfaces based on derived artefacts of applications, namely business entities, we propose heuristics for deriving relations between business entities, and in turn, deriving permissible orders in which operations are invoked. As a result, service operations are refactored on business entity CRUD which then leads to behavioural protocols generated, thus supportive of fine-grained and flexible service discovery, composition and interaction. A prototypical implementation and analysis of web services, including those of commercial logistic systems (Fedex), are used to validate the algorithms and open up further insights into service interface synthesis.

Yhteisön ja yhteiskunnan ehdoilla : Seurakuntien ja kuntien yhteistyö vuorovaikutuksen näkökulmasta

In this research, the cooperation between Finnish municipalities and Evangelical Lutheran parishes is studied from the standpoint of institutional interaction. The most essential theoretical background for the study is the differentiation thesis of the secularization theory. Cooperation from the viewpoints of both organizations is examined using the functional approach. Furthermore, the market theory and other theories are applied in order to place the studied phenomenon in the wider context of the theories of the sociology of religion. Sacralization in modern society and its relationship with the differentiation thesis of the secularization theory are in the theoretical foci. In addition, along with a descriptive examination of cooperation, the normative sides of the phenomenon are discussed. The survey was conducted among all municipalities and parishes in continental Finland. The questionnaires were sent to all municipal managers of youth work and afternoon activities and to all managers of child, youth and social work in the parishes. The response rate for the municipalities was 73.9 % and for the parishes 69.5 %. In addition, two qualitative data were utilized. The aim of the study is to scrutinize what kind of limitations of differentiation can be caused by the interaction between the secular and the religious. In order to solve the problem, an empirical study of sacralization in the modern context is required. For this purpose, the survey was carried out to determine the effects of the religious on the secular and the impact of the secular on the religious. In the articles of the study the following relationships are discussed: the positions of municipalities and parishes in relation to the state and civil society; cooperation in relation to differentiation; sacralization in relation to the differentiation thesis and cooperation in relation to pluralism. The results of the study highlighted the significance of the cooperation, which was contrary to the secularization theory connected to religious sacralization. The acceptance of the appearance of religion in cooperation and parishes support for municipal function was high in municipalities. Religious cooperation was more active than secular cooperation within all fields. This was also true between fields: religiously orientated child work was more active than the societally orientated social work of the church. Religious cooperation in modern fields of activity underlined sacralization. However, the acceptance of sacralization was weaker in cities than rural areas. Positive relationships between the welfare function of municipalities and the religious function of parishes emphasized the incompleteness of differentiation and the importance of sacralization. The relationship of the function of municipalities with parishes was neither negative nor neutral. Thus, in the most active fields, that is, child work and the traditional social work of the church, the orientation of parishes in cooperation supported the functions of both organizations. In more passive fields, that is, youth work and the societal social work of the church, parishes were orientated towards supporting the municipal function. The orientation of municipalities to religion underlined the perception that religious function is necessary for cooperation. However, the official character of cooperation supported accommodation to the requirements of societal pluralism. According to the results, sacralization can be effective also at the institutional level. The religious effect of voluntary cooperation means that religious sacralization can also readjust to modern society. At the same time, the results of the study stressed the importance of institutional autonomy. Thus, the public sector has a central role in successful cooperation. The conditions of cooperation are weakened if there is no official support of cooperation or adjustment to the individual rights of modern society. The results called into question the one-directional assumptions in the secularization paradigm and the modernization theory in the background. In these assumptions, religion that represents the traditional is seen to give way to the modern, especially at the institutional level. Lack of an interactional view was identified as a central weakness of the secularization paradigm. In the theoretical approach created in the study, an interactional view between religious and secular institutions was made possible by limiting the core of the differentiation thesis to autonomy. The counter forces of differentiation are despecialization and sacralization. These changes in the secularization theory bring about new interactivity on the institutional level. In addition to the interactional approach, that is, the secularization and sacralization theory created as a synthesis of the study, interaction between the religious and the secular is discussed from the standpoint of multiple modernities. The spiritual welfare role of religion is seen as a potential supporter of secular institutions. Religion is set theoretically amongst other ideologies and agents, which can create communal bonds in modern society. Key words: cooperation, municipalities, parishes, sacralization, secularization, modernization, multiple modernities, differentiation, interaction, democracy, secularism, pluralism, civil society

Missing-In-Metastasis (MIM) regulates cell morphology by promoting plasma membrane and actin cytoskeleton dynamics

The cells of multicellular organisms have differentiated to carry out specific functions that are often accompanied by distinct cell morphology. The actin cytoskeleton is one of the key regulators of cell shape subsequently controlling multiple cellular events including cell migration, cell division, endo- and exocytosis. A large set of actin regulating proteins has evolved to achieve and tightly coordinate this wide range of functions. Some actin regulator proteins have so-called house keeping roles and are essential for all eukaryotic cells, but some have evolved to meet the requirements of more specialized cell-types found in higher organisms enabling complex functions of differentiated organs, such as liver, kidney and brain. Often processes mediated by the actin cytoskeleton, like formation of cellular protrusions during cell migration, are intimately linked to plasma membrane remodeling. Thus, a close cooperation between these two cellular compartments is necessary, yet not much is known about the underlying molecular mechanisms. This study focused on a vertebrate-specific protein called missing-in-metastasis (MIM), which was originally characterized as a metastasis suppressor of bladder cancer. We demonstrated that MIM regulates the dynamics of actin cytoskeleton via its WH2 domain, and is expressed in a cell-type specific manner. Interestingly, further examination showed that the IM-domain of MIM displays a novel membrane tubulation activity, which induces formation of filopodia in cells. Following studies demonstrated that this membrane deformation activity is crucial for cell protrusions driven by MIM. In mammals, there are five members of IM-domain protein family. Functions and expression patterns of these family members have remained poorly characterized. To understand the physiological functions of MIM, we generated MIM knockout mice. MIM-deficient mice display no apparent developmental defects, but instead suffer from progressive renal disease and increased susceptibility to tumors. This indicates that MIM plays a role in the maintenance of specific physiological functions associated with distinct cell morphologies. Taken together, these studies implicate MIM both in the regulation of the actin cytoskeleton and the plasma membrane. Our results thus suggest that members of MIM/IRSp53 protein family coordinate the actin cytoskeleton:plasma membrane interface to control cell and tissue morphogenesis in multicellular organisms.

A multi-criteria approach for hospital capacity analysis

Hospitals are critical elements of health care systems and analysing their capacity to do work is a very important topic. To perform a system wide analysis of public hospital resources and capacity, a multi-objective optimization (MOO) approach has been proposed. This approach identifies the theoretical capacity of the entire hospital and facilitates a sensitivity analysis, for example of the patient case mix. It is necessary because the competition for hospital resources, for example between different entities, is highly influential on what work can be done. The MOO approach has been extensively tested on a real life case study and significant worth is shown. In this MOO approach, the epsilon constraint method has been utilized. However, for solving real life applications, with a large number of competing objectives, it was necessary to devise new and improved algorithms. In addition, to identify the best solution, a separable programming approach was developed. Multiple optimal solutions are also obtained via the iterative refinement and re-solution of the model.

Microbe-induced activation of inflammatory cytokine response in human cells

Human body is in continuous contact with microbes. Although many microbes are harmless or beneficial for humans, pathogenic microbes possess a threat to wellbeing. Antimicrobial protection is provided by the immune system, which can be functionally divided into two parts, namely innate and adaptive immunity. The key players of the innate immunity are phagocytic white blood cells such as neutrophils, monocytes, macrophages and dendritic cells (DCs), which constantly monitor the blood and peripheral tissues. These cells are armed for rapid activation upon microbial contact since they express a variety of microbe-recognizing receptors. Macrophages and DCs also act as antigen presenting cells (APCs) and play an important role in the development of adaptive immunity. The development of adaptive immunity requires intimate cooperation between APCs and T lymphocytes and results in microbe-specific immune responses. Moreover, adaptive immunity generates immunological memory, which rapidly and efficiently protects the host from reinfection. Properly functioning immune system requires efficient communication between cells. Cytokines are proteins, which mediate intercellular communication together with direct cell-cell contacts. Immune cells produce inflammatory cytokines rapidly following microbial contact. Inflammatory cytokines modulate the development of local immune response by binding to cell surface receptors, which results in the activation of intracellular signalling and modulates target cell gene expression. One class of inflammatory cytokines chemokines has a major role in regulating cellular traffic. Locally produced inflammatory chemokines guide the recruitment of effector cells to the site of inflammation during microbial infection. In this study two key questions were addressed. First, the ability of pathogenic and non-pathogenic Gram-positive bacteria to activate inflammatory cytokine and chemokine production in different human APCs was compared. In these studies macrophages and DCs were stimulated with pathogenic Steptococcus pyogenes or non-pathogenic Lactobacillus rhamnosus. The second aim of this thesis work was to analyze the role of pro-inflammatory cytokines in the regulation of microbe-induced chemokine production. In these studies bacteria-stimulated macrophages and influenza A virus-infected lung epithelial cells were used as model systems. The results of this study show that although macrophages and DCs share several common antimicrobial functions, these cells have significantly distinct responses against pathogenic and non-pathogenic Gram-positive bacteria. Macrophages were activated in a nearly similar fashion by pathogenic S. pyogenes and non-pathogenic L. rhamnosus. Both bacteria induced the production of similar core set of inflammatory chemokines consisting of several CC-class chemokines and CXCL8. These chemokines attract monocytes, neutrophils, dendritic cells and T cells. Thus, the results suggest that bacteria-activated macrophages efficiently recruit other effector cells to the site of inflammation. Moreover, macrophages seem to be activated by all bacteria irrespective of their pathogenicity. DCs, in contrast, were efficiently activated only by pathogenic S. pyogenes, which induced DC maturation and production of several inflammatory cytokines and chemokines. In contrast, L. rhamnosus-stimulated DCs matured only partially and, most importantly, these cells did not produce inflammatory cytokines or chemokines. L. rhamnosus-stimulated DCs had a phenotype of "semi-mature" DCs and this type of DCs have been suggested to enhance tolerogenic adaptive immune responses. Since DCs have an essential role in the development of adaptive immune response the results suggest that, in contrast to macrophages, DCs may be able to discriminate between pathogenic and non-pathogenic bacteria and thus mount appropriate inflammatory or tolerogenic adaptive immune response depending on the microbe in question. The results of this study also show that pro-inflammatory cytokines can contribute to microbe-induced chemokine production at multiple levels. S. pyogenes-induced type I interferon (IFN) was found to enhance the production of certain inflammatory chemokines in macrophages during bacterial stimulation. Thus, bacteria-induced chemokine production is regulated by direct (microbe-induced) and indirect (pro-inflammatory cytokine-induced) mechanisms during inflammation. In epithelial cells IFN- and tumor necrosis factor- (TNF-) were found to enhance the expression of PRRs and components of cellular signal transduction machinery. Pre-treatment of epithelial cells with these cytokines prior to virus infection resulted in markedly enhanced chemokine response compared to untreated cells. In conclusion, the results obtained from this study show that pro-inflammatory cytokines can enhance microbe-induced chemokine production during microbial infection by providing a positive feedback loop. In addition, pro-inflammatory cytokines can render normally low-responding cells to high chemokine producers via enhancement of microbial detection and signal transduction.