Structure-activity relationships from in vitro efficacies of the thiazolide series against the intracellular apicomplexan protozoan Neospora caninum

Nitazoxanide (2-acetolyloxy-N-(5-nitro 2-thiazolyl) benzamide; NTZ) represents the parent compound of a novel class of broad-spectrum anti-parasitic compounds named thiazolides. NTZ is active against a wide variety of intestinal and tissue-dwelling helminths, protozoa, enteric bacteria and a number of viruses infecting animals and humans. While potent, this poses a problem in practice, since this obvious non-selectivity can lead to undesired side effects in both humans and animals. In this study, we used real time PCR to determine the in vitro activities of 29 different thiazolides (NTZ-derivatives), which carry distinct modifications on both the thiazole- and the benzene moieties, against the tachyzoite stage of the intracellular protozoan Neospora caninum. The goal was to identify a highly active compound lacking the undesirable nitro group, which would have a more specific applicability, such as in food animals. By applying self-organizing molecular field analysis (SOMFA), these data were used to develop a predictive model for future drug design. SOMFA performs self-alignment of the molecules, and takes into account the steric and electrostatic properties, in order to determine 3D-quantitative structure activity relationship models. The best model was obtained by overlay of the thiazole moieties. Plotting of predicted versus experimentally determined activity produced an r2 value of 0.8052 and cross-validation using the "leave one out" methodology resulted in a q2 value of 0.7987. A master grid map showed that large steric groups at the R2 position, the nitrogen of the amide bond and position Y could greatly reduce activity, and the presence of large steric groups placed at positions X, R4 and surrounding the oxygen atom of the amide bond, may increase the activity of thiazolides against Neospora caninum tachyzoites. The model obtained here will be an important predictive tool for future development of this important class of drugs.

Gene expression in cortex and hippocampus during acute pneumococcal meningitis

BACKGROUND: Pneumococcal meningitis is associated with high mortality (approximately 30%) and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown.We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i) a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI) and (ii) the self-organizing map (SOM), a clustering technique based on covariance in gene expression kinetics. RESULTS: Among 598 genes differentially regulated (change factor > or = 1.5; p < or = 0.05), 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic. CONCLUSION: Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential targets for therapy.

Using Context Information to Re-architect a System

Successful software systems cope with complexity by organizing classes into packages. However, a particular organization may be neither straightforward nor obvious for a given developer. As a consequence, classes can be misplaced, leading to duplicated code and ripple effects with minor changes effecting multiple packages. We claim that contextual information is the key to rearchitecture a system. Exploiting contextual information, we propose a technique to detect misplaced classes by analyzing how client packages access the classes of a given provider package. We define locality as a measure of the degree to which classes reused by common clients appear in the same package. We then use locality to guide a simulated annealing algorithm to obtain optimal placements of classes in packages. The result is the identification of classes that are candidates for relocation. We apply the technique to three applications and validate the usefulness of our approach via developer interviews.

Building the New Society in the Shell of the Old: Finnish-Canadian Hall Socialism and the Canadian Industrial Unionist Support League

The literature on Finnish immigrant working-class movements in North America frequently makes reference to the phenomenon of "hall socialism," so-called because of the central position that the socialist or labor hall occupied in the political, associational, and cultural life of many Finnish communities throughout the twentieth-century. In the 1930s, over 80 such Finnish halls were spread across Canada, and many people associated with these halls vigorously supported the mission of organized labor. This paper will examine the history, ideas, and practices of the Industrial Workers of the World-influenced Canadan Teollisuusunionistien Kannatus Liitto (CTKL; Canadian Industrial Unionist Support League), and its connections to Finnish Canadian hall socialism. The paper will consider the role of the CTKL in supporting workers' struggles, the significance of the hall as a part of the infrastructural bedrock that sustained this support, and the broader interaction between social and radical organizing commitments.

Our Lives, Our Thoughts and Our Allegiance: New Immigrants and American Industry in 1914

Through comparative analysis of the immigrant labor forces at work in iron mining in northern Minnesota, coal mining in Illinois, and steel milling in the Calumet region of Chicago and Gary, this paper addresses the forms of social distance separating and marginalizing new immigrants from American society and trade unionism that existed in 1914, the year that marked the end point of mass immigration from Eastern and Southern Europe. The “new immigration” was a labor migration that congregated its subjects overwhelmingly in what were called "unskilled" or "semi-skilled" forms of labor. Skilled work was largely, with certain variations, the preserve of "American" or old immigrant workers. This labor gulf separating new immigrants and American workers was hardened by a spatial separateness. New immigrants often lived in what have been called industrial villages—the mining town or location, the factory neighborhood— striking in their isolation and insularity from mainstream society. This separateness and insularity became a major preoccupation for corporate managers, Progressive reformers, and for American trade unions as new immigrants began to engage in major labor struggles leading up to 1914. But among the three industries, only the union of coal miners, the United Mine Workers, enjoyed success in organizing the new immigrants. In the steel mills and the iron mines, the unions were either rooted out or failed to gain a foothold at all. The explanation for these differences is to be found in the different forms of industrial development among the industries studied.

ANIMATED TRANSITION IN SIMILARITY-BASED TILED IMAGE LAYOUT

Effective techniques for organizing and visualizing large image collections are in growing demand as visual search gets increasingly popular. iMap is a treemap representation for visualizing and navigating image search and clustering results based on the evaluation of image similarity using both visual and textual information. iMap not only makes effective use of available display area to arrange images but also maintains stable update when images are inserted or removed during the query. A key challenge of using iMap lies in the difficult to follow and track the changes when updating the image arrangement as the query image changes. For many information visualization applications, showing the transition when interacting with the data is critically important as it can help users better perceive the changes and understand the underlying data. This work investigates the effectiveness of animated transition in a tiled image layout where the spiral arrangement of the images is based on their similarity. Three aspects of animated transition are considered, including animation steps, animation actions, and flying paths. Exploring and weighting the advantages and disadvantages of different methods for each aspect and in conjunction with the characteristics of the spiral image layout, we present an integrated solution, called AniMap, for animating the transition from an old layout to a new layout when a different image is selected as the query image. To smooth the animation and reduce the overlap among images during the transition, we explore different factors that might have an impact on the animation and propose our solution accordingly. We show the effectiveness of our animated transition solution by demonstrating experimental results and conducting a comparative user study.

A STUDY ON REGIONAL CIRCULAR ECONOMY SYSTEM AND ITS CONSTRUCTION, OPERATION AND SUGGESTION FOR SHANGHAI

The characteristics of the traditional linear economic model are high consumption, high emission and low efficiency. Economic development is still largely at the expense of the environment and requires a natural resource investment. This can realize rapid economic development but resource depletion and environmental pollution become increasingly serious. In the 1990's a new economic model, circular economics, began to enter our vision. The circular economy maximizes production and minimizes the impact of economic activities on the ecological environment through organizing the activities through the closed-loop feedback cycle of "resources - production - renewable resource". Circular economy is a better way to solve the contradictions between the economic development and resource shortages. Developing circular economy has become the major strategic initiatives to achieving sustainable development in countries all over the world. The evaluation of the development of circular economics is a necessary step for regional circular economy development. Having a quantitative evaluation of circular economy can better monitor and reveal the contradictions and problems in the process of the development of recycling economy. This thesis will: 1) Create an evaluation model framework and new types of industries and 2) Make an evaluation of the Shanghai circular economy currently to analyze the situation of Shanghai in the development of circular economy. I will then propose suggestions about the structure and development of Shanghai circular economy.

Radiation metabolomics. 1. Identification of minimally invasive urine biomarkers for gamma-radiation exposure in mice

Gamma-radiation exposure has both short- and long-term adverse health effects. The threat of modern terrorism places human populations at risk for radiological exposures, yet current medical countermeasures to radiation exposure are limited. Here we describe metabolomics for gamma-radiation biodosimetry in a mouse model. Mice were gamma-irradiated at doses of 0, 3 and 8 Gy (2.57 Gy/min), and urine samples collected over the first 24 h after exposure were analyzed by ultra-performance liquid chromatography-time-of-flight mass spectrometry (UPLC-TOFMS). Multivariate data were analyzed by orthogonal partial least squares (OPLS). Both 3- and 8-Gy exposures yielded distinct urine metabolomic phenotypes. The top 22 ions for 3 and 8 Gy were analyzed further, including tandem mass spectrometric comparison with authentic standards, revealing that N-hexanoylglycine and beta-thymidine are urinary biomarkers of exposure to 3 and 8 Gy, 3-hydroxy-2-methylbenzoic acid 3-O-sulfate is elevated in urine of mice exposed to 3 but not 8 Gy, and taurine is elevated after 8 but not 3 Gy. Gene Expression Dynamics Inspector (GEDI) self-organizing maps showed clear dose-response relationships for subsets of the urine metabolome. This approach is useful for identifying mice exposed to gamma radiation and for developing metabolomic strategies for noninvasive radiation biodosimetry in humans.

Mapping of direction and muscle representation in the human primary motor cortex controlling thumb movements

Larger body parts are somatotopically represented in the primary motor cortex (M1), while smaller body parts, such as the fingers, have partially overlapping representations. The principles that govern the overlapping organization of M1 remain unclear. We used transcranial magnetic stimulation (TMS) to examine the cortical encoding of thumb movements in M1 of healthy humans. We performed M1 mapping of the probability of inducing a thumb movement in a particular direction and used low intensity TMS to disturb a voluntary thumb movement in the same direction during a reaction time task. With both techniques we found spatially segregated representations of the direction of TMS-induced thumb movements, thumb flexion and extension being best separated. Furthermore, the cortical regions corresponding to activation of a thumb muscle differ, depending on whether the muscle functions as agonist or as antagonist for flexion or extension. In addition, we found in the reaction time experiment that the direction of a movement is processed in M1 before the muscles participating in it are activated. It thus appears that one of the organizing principles for the human corticospinal motor system is based on a spatially segregated representation of movement directions and that the representation of individual somatic structures, such as the hand muscles, overlap.

Neighbourhoods Mobilise the Troops - Community Organising, Violence and Governmentality

The article reflects on the difficult relation between community work against domestic violence and local crime prevention under the conditions of the neoliberal state that cuts down on social benefits and promotes self-help, active citizenship and self-responsibility instead while at the same time restoring the punishing state with its strict regime of law-and-order. The author describes a project Tarantula - she started herself while being a social worker in Hamburg, Germany. Tarantula was aimed at strengthening social networks and the neighbours' willingness to get involved in favour of affected women. Although conceptualized as an emancipatory approach referring to community organizing in the tradition of social movements it is questionable whether and how this can really work in the current situation. At present, the field of crime control is being reconfigured as a result of political and administrative decisions, which, for their part, are based on a new structure of social relations and cultural attitudes. The demolition of the 'welfare state' means the re-coding of the security policy that facilitates the development of interventionist techniques that govern and control individuals through their own ability to act.

Libre Courseware For Bayesian Decision Making

This paper describes the ideas and problems of the Edukalibre e-learning project, in which the author takes part. The basic objective of the project shares the development and exploitation of software components for web-based information systems applied to education as well as organizing of teaching material for them. The paper concerns a problem of the mathematical-oriented courseware and describes the experience in developing LaTeX-supporting online converting tool.

Adaptive Materialbereitstellung in flexiblen Produktionssystemen auf Grundlage einer agentenbasierten Transportsteuerung

Zur Sicherstellung einer schnellen und flexiblen Anpassung an sich ändernde Anforderungen sind innerbetriebliche Materialbereitstellungskonzepte in immer stärkerem Maße zu flexibilisieren. Hierdurch kann die Erreichung logistischer Ziele in einem dynamischen Produktionsumfeld gesteigert werden. Der Beitrag stellt ein Konzept für eine adaptive Materialbereitstellung in flexiblen Produktionssystemen auf Grundlage einer agentenbasierten Transportplanung und -steuerung vor. Der Fokus liegt hierbei auf der Planung und Steuerung der auf Basis von Materialbedarfsmeldungen ausgelösten innerbetrieblichen Transporte. Neben Pendeltouren zur Versorgung des Produktionssystems findet auch das dynamische Pickup-and-Delivery-Problem Berücksichtigung. Das vorgestellte Konzept ist an den Anforderungen selbstorganisierender Produktionsprozesse ausgerichtet.

Science for the Carpathians: Using Regional Capacity to Cope with Global Change

Emphasizing the global and regional importance of mountain ecosystem services and referring to the anticipated future environmental changes affecting the provision of these services, this chapter takes a closer look at the Carpathian Mountains. In addition to climate change and general effects of globalization, rapid socioeconomic transformations after the fall of the Iron Curtain pose an extra challenge to the sustainable development of the region. Describing the early efforts of organizing mountain science through programs such as UNESCO MAB and UNEP at the global scale, this chapter focuses on the recent history of research coordination for the European mountains, in particular on the activities of the Carpathian Convention and the European Program of the Mountain Research Initiative, which were among main driving factors for the initiation of the Science for the Carpathians (S4C) network. This regional mountain research network was established in 2008 to foster scientific collaboration and communication and to promote applied research and capacity building, which in turn would support sustainable development in the Carpathian Mountains. Forum Carpaticum, a biennial open science conference, has become a central activity of the S4C network counting more than 400 members today.

The Interplay of Power and Trust in Platform Ecosystems of the Enterprise Application Software Industry

In recent years, the formerly oligopolistic Enterprise Application Software (EAS) industry began to disintegrate into focal inter-firm networks with one huge, powerful, and multi-national plat-form vendor as the center, surrounded by hundreds or even thousands of small, niche players that act as complementors. From a theoretical point of view, these platform ecosystems may be governed by two organizing principles - trust and power. However, it is neither from a practical nor from a theoretical perspective clear, how trust and power relate to each other, i.e. whether they act as complements or substitutes. This study tries to elaborate our understanding of the relationship of trust and power by exploring their interplay using multi-dimensional conceptual-izations of trust and power, and by investigating potential dynamics in this interplay over the course of a partnership. Based on an exploratory multiple-case study of seven dyadic partner-ships between four platform vendors, and seven complementors, we find six different patterns of how trust and power interact over time. These patterns bear important implications for the suc-cessful management of partnerships between platform vendors and complementors, and clarify the theoretical debate surrounding the relationship of trust and power.