A new rodent model to assess blood stage immunity to the plasmodium falciparum antigen merozoite surface protein 119 reveals a protective role for invasion inhibitory antibodies

Antibodies capable of inhibiting the invasion of Plasmodium merozoites into erythrocytes are present in individuals that are clinically immune to the malaria parasite. Those targeting the 19-kD COOH-terminal domain of the major merozoite surface protein (MSP)-119 are a major component of this inhibitory activity. However, it has been difficult to assess the overall relevance of such antibodies to antiparasite immunity. Here we use an allelic replacement approach to generate a rodent malaria parasite (Plasmodium berghei) that expresses a human malaria (Plasmodium falciparum) form of MSP-119. We show that mice made semi-immune to this parasite line generate high levels of merozoite inhibitory antibodies that are specific for P. falciparum MSP-119. Importantly, protection from homologous blood stage challenge in these mice correlated with levels of P. falciparum MSP-119–specific inhibitory antibodies, but not with titres of total MSP-119–specific immunoglobulins. We conclude that merozoite inhibitory antibodies generated in response to infection can play a significant role in suppressing parasitemia in vivo. This study provides a strong impetus for the development of blood stage vaccines designed to generate invasion inhibitory antibodies and offers a new animal model to trial P. falciparum MSP-119 vaccines.

Sindbis virus vectors elicit hemagglutinin-specific humoral and cellular immune responses and offer a dose-sparing strategy for vaccination

We report here on the use of a Sindbis virus-based DNA-launch RNA replicon vector (pSIN-HA) that expresses influenza hemagglutinin (HA) as an immunogen. Immunization of mice with pSIN-HA generated anti-HA antibody and CTL responses and resulted in lower lung viral titers after influenza challenge when compared to controls. Importantly, immunization with a low dose of pSIN-HA mediated significantly reduced lung viral titers following challenge at 43 weeks after the final immunization. In contrast, immunization with a non-replicon DNA vector expressing HA failed to mediate reduced lung viral titer at the same dose. This demonstrated the dose-sparing capacity of the SIN vector system and its ability to stimulate long-term memory responses, properties that are highly desirable in any vaccine formulation.

Doing the ultimate public good through teacher education

It is argued here that the many public goods associated with education are derivatives of an ultimate good. This ultimate good is the overall purpose of life in general and is similar to a telos as understood in ancient Greek culture. This paper reviews the notions of ‘good' and telos, and examines implications of Bauman’s analysis of our present individualizing era, the role of personal meaning making and the nature of education. It is then argued that preservice teachers can do the ultimate public good in a postmodern society, by articulating a developed personal, professional perspective that expresses a purpose (telos) of life.

Multi-media and real fiction theatre making

Visual images, in the process of both the imagination and conception of a theatre production, are central to contemporary practice in drama-making. The use of multi-media in theatre is not only a fruitful way to represent the visual component of a particular experience, it but also constitutes a way of speaking the unspoken. Visual language expresses through multi-media and allows broaching taboo subjects, speaking directly to the audience in spite of the indirect form and drawing subtle connections with the live action so as to make meaning. The tension between live action and any form of visual art blurs the lines between imagination and reality. The multi-media theatre is a metaphor for the human mind exposed to social reality. It consists of interruptions, half-finished conversations and ideological aspersions including its primary function of meta-representation.

Functional analysis of the leading malaria vaccine candidate AMA-1 reveals an essential role for the cytoplasmic domain in the invasion process

A key process in the lifecycle of the malaria parasite Plasmodium falciparum is the fast invasion of human erythrocytes. Entry into the host cell requires the apical membrane antigen 1 (AMA-1), a type I transmembrane protein located in the micronemes of the merozoite. Although AMA-1 is evolving into the leading blood-stage malaria vaccine candidate, its precise role in invasion is still unclear. We investigate AMA-1 function using live video microscopy in the absence and presence of an AMA-1 inhibitory peptide. This data reveals a crucial function of AMA-1 during the primary contact period upstream of the entry process at around the time of moving junction formation. We generate a Plasmodium falciparum cell line that expresses a functional GFP-tagged AMA-1. This allows the visualization of the dynamics of AMA-1 in live parasites. We functionally validate the ectopically expressed AMA-1 by establishing a complementation assay based on strain-specific inhibition. This method provides the basis for the functional analysis of essential genes that are refractory to any genetic manipulation. Using the complementation assay, we show that the cytoplasmic domain of AMA-1 is not required for correct trafficking and surface translocation but is essential for AMA-1 function. Although this function can be mimicked by the highly conserved cytoplasmic domains of P. vivax and P. berghei, the exchange with the heterologous domain of the microneme protein EBA-175 or the rhoptry protein Rh2b leads to a loss of function. We identify several residues in the cytoplasmic tail that are essential for AMA-1 function. We validate this data using additional transgenic parasite lines expressing AMA-1 mutants with TY1 epitopes. We show that the cytoplasmic domain of AMA-1 is phosphorylated. Mutational analysis suggests an important role for the phosphorylation in the invasion process, which might translate into novel therapeutic strategies.

Robust-diagnostic regression : a prelude for inducing reliable knowledge from regression

Regression lies heart in statistics, it is the one of the most important branch of multivariate techniques available for extracting knowledge in almost every field of study and research. Nowadays, it has drawn a huge interest to perform the tasks with different fields like machine learning, pattern recognition and data mining. Investigating outlier (exceptional) is a century long problem to the data analyst and researchers. Blind application of data could have dangerous consequences and leading to discovery of meaningless patterns and carrying to the imperfect knowledge. As a result of digital revolution and the growth of the Internet and Intranet data continues to be accumulated at an exponential rate and thereby importance of detecting outliers and study their costs and benefits as a tool for reliable knowledge discovery claims perfect attention. Investigating outliers in regression has been paid great value for the last few decades within two frames of thoughts in the name of robust regression and regression diagnostics. Robust regression first wants to fit a regression to the majority of the data and then to discover outliers as those points that possess large residuals from the robust output whereas in regression diagnostics one first finds the outliers, delete/correct them and then fit the regular data by classical (usual) methods. At the beginning there seems to be much confusion but now the researchers reach to the consensus, robustness and diagnostics are two complementary approaches to the analysis of data and any one is not good enough. In this chapter, we discuss both of them under the unique spectrum of regression diagnostics. Chapter expresses the necessity and views of regression diagnostics as well as presents several contemporary methods through numerical examples in linear regression within each aforesaid category together with current challenges and possible future research directions. Our aim is to make the chapter self-explained maintaining its general accessibility.

Ambient thing full length

Ambient Thing is an uplifting, melodic and motivational track featuring synths, piano, guitar, double bass, violins, drums and light vocals. Atmospheric and reflective, yet incredibly inspiring, It expresses positivity, strong emotional connection and success. Upbeat and positive, it is suitable for your business/corporate projects, videos, websites, films, creative pursuits and more.

Ambient thing loop

Ambient Thing is an uplifting, melodic and motivational track featuring synths, drums and light vocals. Atmospheric and reflective, yet incredibly inspiring, it expresses positivity, strong emotional connection and success. Upbeat and positive, it is suitable for your business/corporate projects, videos, websites, films, creative pursuits and more.

Ambient thing loop 2

Ambient Thing is an uplifting, melodic and motivational track featuring synths, piano,drums. Atmospheric and reflective, yet incredibly inspiring, it expresses positivity, strong emotional connection and success. Upbeat and positive, it is suitable for your business/corporate projects, videos, websites, films, creative pursuits and more.

Ambient thing loop 3

Ambient Thing is an uplifting, melodic and motivational track featuring synths, piano,drums. Atmospheric and reflective, yet incredibly inspiring, it expresses positivity, strong emotional connection and success. Upbeat and positive, it is suitable for your business/corporate projects, videos, websites, films, creative pursuits and more.

Role assessment of GIS analysis and its reliability while ranking urban sustainability using scenarios specific to regional climate, community and culture

Urban Sustainability expresses the level of conservation of a city while living a town or consuming its urban resources, but the measurement of urban sustainability depends on what are considered important indicators of conservation besides the permitted levels of consumption in accordance with adopted criteria. This criterion should have common factors that are shared for all the members tested or cities to be evaluated as in this particular case for Abu Dhabi, but also have specific factors that are related to the geographic place, community and culture, that is the measures of urban sustainability specific to a middle east climate, community and culture where GIS Vector and Raster analysis have a role or add a value in urban sustainability measurements or grading are considered herein. Scenarios were tested using various GIS data types to replicate urban history (ten years period), current status and expected future of Abu Dhabi City setting factors to climate, community needs and culture. The useful Vector or Raster GIS data sets that are related to every scenario where selected and analysed in the sense of how and how much it can benefit the urban sustainability ranking in quantity and quality tests, this besides assessing the suitable data nature, type and format, the important topology rules to be considered, the useful attributes to be added, the relationships which should be maintained between data types of a geo- database, and specify its usage in a specific scenario test, then setting weights to each and every data type representing some elements of a phenomenon related to urban suitability factor. The results of assessing the role of GIS analysis provided data collection specifications such as the measures of accuracy reliable to a certain type of GIS functional analysis used in an urban sustainability ranking scenario tests. This paper reflects the prior results of the research that is conducted to test the multidiscipline evaluation of urban sustainability using different indicator metrics, that implement vector GIS Analysis and Raster GIS analysis as basic tools to assist the evaluation and increase of its reliability besides assessing and decomposing it, after which a hypothetical implementation of the chosen evaluation model represented by various scenarios was implemented on the planned urban sustainability factors for a certain period of time to appraise the expected future grade of urban sustainability and come out with advises associated with scenarios for assuring gap filling and relative high urban future sustainability. The results this paper is reflecting are concentrating on the elements of vector and raster GIS analysis that assists the proper urban sustainability grading within the chosen model, the reliability of spatial data collected; analysis selected and resulted spatial information. Starting from selecting some important indicators to comprise the model which include regional culture, climate and community needs an example of what was used is Energy Demand & Consumption (Cooling systems). Thus, this factor is related to the climate and it‟s regional specific as the temperature varies around 30-45 degrees centigrade in city areas, GIS 3D Polygons of building data used to analyse the volume of buildings, attributes „building heights‟, estimate the number of floors from the equation, following energy demand was calculated and consumption for the unit volume, and compared it in scenario with possible sustainable energy supply or using different environmental friendly cooling systems this is followed by calculating the cooling system effects on an area unit selected to be 1 sq. km, combined with the level of greenery area, and open space, as represented by parks polygons, trees polygons, empty areas, pedestrian polygons and road surface area polygons. (initial measures showed that cooling system consumption can be reduced by around 15 -20 % with a well-planned building distributions, proper spaces and with using environmental friendly products and building material, temperature levels were also combined in the scenario extracted from satellite images as interpreted from thermal bands 3 times during the period of assessment. Other examples of the assessment of GIS analysis to urban sustainability took place included Waste Productivity, some effects of greenhouse gases measured by the intensity of road polygons and closeness to dwelling areas, industry areas as defined from land use land cover thematic maps produced from classified satellite images then vectors were created to take part in defining their role within the scenarios. City Noise and light intensity assessment was also investigated, as the region experiences rapid development and noise is magnified due to construction activities, closeness of the airports, and highways. The assessment investigated the measures taken by urban planners to reduce degradation or properly manage it. Finally as a conclusion tables were presented to reflect the scenario results in combination with GIS data types, analysis types, and the level of GIS data reliability to measure the sustainability level of a city related to cultural and regional demands.

The humanities curriculum in a changing world

In this article Harvie discusses the perceptions that pre-service teachers have about Humanities teaching & learning.Harvie expresses the importance of a sound humanities program in schools is central to developing individual members of society that are informed about Values, Citizenship, Australian and Global History, Geography and Economics.

Representative actions, proof of fact and author identification in copyright law: a history and a concern

Recent judgments in Australia have called for author identification in order that copyright subsistence may be established. There is a risk that such calls will be taken too literally, to the detriment of author privacy. This article considers the legal mechanisms by which author identity has historically been shielded from disclosure, without the operation of the copyright system being impaired. It expresses the hope that those who are responsible for developing copyright law will be mindful of the concern for author privacy which has long been part of copyright discourse.

Introduction: secularization and its discontents

Sigmund Freud’s 1927 work The Future of Illusion expresses the great psychoanalyst’s most whiggish assessment of the situation of Western, post-enlightenment societies. In it, Freud reanimates the ancient tradition of the materialist-Epicurean criticism of religion, with its skepticism concerning all invisible powers. For Freud, famously, the religious belief in higher, supernatural deities—particularly, the monotheistic God—represents a wish-fulfillment and illusion (Freud 1927: 30, 43). This illusion takes its particular shapes from our earliest childhood experiences of helplessness, and the longing for an all-protecting, omnibenevolent father. With the progress of science, and its benefits in technology, Freud opined that the period of the cultural pre-eminence of religion in the West was over. Civilization and its Discontents, written 3 years later, expresses a similarly sceptical assessment of religion. Whether founded in an oceanic, mystical sentiment of oneness, or the refined language of the theologians, religion remains for Freud ‘patently infantile’ (Freud 1930: 86). Between 1927 and 1930, however, Freud’s assessment of the wider prospects of modern Kultur shifted, if it did not entirely reverse. With the fortunes of fascism rising, and the first clouds of renewed European war forming on the horizon, Freud now argues that the psychological price demanded by the modern world’s manifold civilizational advances is perhaps too high. The sexual and aggressive impulses modern society demands subjects renounce must return in the forms of organized violence, collective and individual neuroses—and in the same form of unconscious guilt Freud had argued elsewhere animated the totems and taboos of the great religions (Freud 1913, 1938). Although Freud did not draw the conclusion, the logic of his wider Kulturpessimismus points to the claim that the psychologically deep-set ‘illusions’ of religion could expect a long and viable future.

A new approach based on support vector machine for solving stochastic optimization

Making decision usually occurs in the state of being uncertain. These kinds of problems often expresses in a formula as optimization problems. It is desire for decision makers to find a solution for optimization problems. Typically, solving optimization problems in uncertain environment is difficult. This paper proposes a new hybrid intelligent algorithm to solve a kind of stochastic optimization i.e. dependent chance programming (DCP) model. In order to speed up the solution process, we used support vector machine regression (SVM regression) to approximate chance functions which is the probability of a sequence of uncertain event occurs based on the training data generated by the stochastic simulation. The proposed algorithm consists of three steps: (1) generate data to estimate the objective function, (2) utilize SVM regression to reveal a trend hidden in the data (3) apply genetic algorithm (GA) based on SVM regression to obtain an estimation for the chance function. Numerical example is presented to show the ability of algorithm in terms of time-consuming and precision.