bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensory Extension as a Tool for Cognitive Learning
Authors: Eisenberg Michael , Eisenberg Ann
Published: April 2015

The practice of educational technology has long been driven by a relatively restricted set of operational metaphors: typically, computers are identified as potential “teachers” or “tutors” of material or (arguably more productively) as “learning tools” for students. Recent developments in technology suggest the advent of another, perhaps still more fruitful metaphor – namely viewing educational technology (not limited to computers) as a means of sensory extension. In this view, technology is seen not as a repository of content, but rather as an extension of scientific instrumentation (telescopes, microscopes, bubble chambers) and prosthetics (eyeglasses, cochlear implants). This chapter is intended as an initial, partly speculative exploration of what it would mean for science and arts education to rethink the role of technology in terms of sensory extension rather than classroom instruction.
Visualization and Mathematical Thinking
Authors: Lehning Hervé
Published: April 2015

Drawing is not proving. For a long time, this argument has been used to avoid the use of visualization in mathematics. Nevertheless, a number of proofs, concepts, and ideas are easier to understand with the help of a small drawing. In this chapter, the author shows that visualization in mathematics is helpful not only to illustrate but also to create ideas, and this at all levels.
Science of the Archives
Authors: Flannery Maura C.
Published: April 2015

This chapter deals with the history of plant collections and their uses in science and art. It does this within the context of the development of a visual literacy about plants and their structures. It also covers how the value and influence of these collections are increasing as they become available electronically. These resources are now accessible not only to plant biologists but also to gardeners, environmentalists, naturalists, and students. Included here is a discussion of the various online portals that have been created, their relative usefulness to nonprofessionals, and how they can be “tamed” by educators to make them useful and useable tools for students.
Visualization by Coding
Authors: Ursyn Anna , Mostowfi Mehrgan
Published: April 2015

The authors present image transformations that allow for checking and better understanding the graphical capacities of various languages and the place of programming in artistic production. The goal of this tutorial-style chapter is to introduce curious artists to basic programming concepts such as variables, arrays, loops, condition structures, classes, and functions through coding visualization of a simple 2-dimensional shape, a horse rider. At the same time, the goal is to make computer scientists more comfortable with the visual ways of dealing with concepts and objects to be programmed. How more complicated digital art can be produced through transformation using programming is also briefly discussed. Pointers to more advanced artistic techniques are also given. These techniques use transformations of code-driven lines to turn them into sculptures, photo silkscreens, photolithographs, knitted fractals, etc.
Connecting the Dots
Authors: Zhou Jing
Published: April 2015

This chapter presents the motivation, background, and implementation of Living Mandala: The Cosmic of Being1, an interactive graphics installation that combines real-time data, multi-cultural mandalas, scientific imagery, and cosmological symbols. Built with an open source programming language and environment, this living contemporary symbol is an exploration into uncharted territories of the human soul sculpted by our present time. Its interactive revolving graphical system visualizes our perceptions of life (microcosm) and the universe (macrocosm), our connections to ancient mythology, cosmology, and cultural heritage, and the relationships among humankind, science, technology, and nature in a globalized society. Merging rich historical, cultural, and scientific imagery and symbols with real-time data and relaxing sound, this living organism alters every moment responding to the movement, color, light, sound, and temperature of its surroundings.2
Re-Visualising Giotto's 14th-Century Assisi Fresco “Exorcism of the Demons at Arezzo”
Authors: Wyeld Theodor G.
Published: April 2015

In this chapter, Giotto's Assisi fresco, “Exorcism of the Demons at Arezzo,” was modelled and analysed in three-dimensions. The process revealed that Giotto's techniques for creating the illusion of depth in his paintings were more advanced than initially thought. His Exorcism fresco was chosen as it is often heralded as an exemplar of the initial shift to the later perspective style of the Renaissance proper. The 3D modelling of the fresco revealed much that could not be deduced by other means. An aerial view of the architectural elements in his fresco shows Giotto's ordered urban layout. That a fully perspective view can be generated, which closely matches the original fresco, suggests a deeper understanding of the geometric construction of depth cues in Giotto's work than previously reported.
Visualization in Learning
Authors: Osinska Veslava , Osinski Grzegorz , Kwiatkowska Anna Beata
Published: April 2015

Visualization is currently used as a data analysis tool and considered a way of communicating knowledge and ideas in many areas of life such as science, education, medicine, marketing, and advertisement. The chapter contains complex interdisciplinary material and attempts to construct a general framework of visualization roles in learning. The structure of this content is presented on Figure 1 as a kind of mind map. Authors emphasize that visualization mechanisms are designed taking into account analytical and content-related potential, timeliness, online availability, and aesthetics. But classical (tabular) forms still remain dominant in information presentation. A good portion of the discussion is dedicated to the alternative solution – non-linear layout, such as network or fractals. Several visualization maps with specifically designed architecture are demonstrated as important elements of contemporary education. Authors consider the potential and implementation of these tools in e-learning platforms. Parallely, they underline the role of interdisciplinary collaboration in map making processes. Researchers in different fields can apply contemporary trends in visualization including natural shape perception, 3D representation problems, as well as the aspects of neuroaesthetics.
Analyzing Disney's Early Exhibits as Installation Art Work
Authors: Lillie Jonathan , Jones-Lillie Michelle
Published: April 2015

This chapter compares several Disney exhibits—particularly those narrativizing technological innovation—to immersive installation artwork in order to explore the importance of narrative and textual reference in creating powerful immersive installations as presentation of technological and scientific knowledge through multiple media. The narrative craft of exhibits such as the Ford Magic Skyway and GE Carousel of Progress, which Disney created for the 1964-65 World's Fair in New York, are compared to works within the genre of installation art, which has developed greatly since the 1960s. Similar to Disney, many artists have deployed immersive installation art exhibits to envelop audiences in a detailed aesthetic and conceptual narrative. Some educational institutions have also used experiential education installations, especially for teaching scientific concepts.
On Creativity of Asian and American Asian Students
Authors: Pyune Joohyun
Published: April 2015

This chapter examines ways to encourage Asian and American Asian students to learn how to use their creativity and develop their independent cognitive thinking skills. It is greatly beneficial for the Asian American students to embrace and understand both cultures. Exercises are described that are designed to help students improve their creative thinking skills and combine ideas from both their cultures naturally. Further discussion is proposed that would analyze the presumed students' thought processes and define future assessment of the efficiency of particular exercises by testing students' solutions and abilities.
AiryLight
Authors: Berner Annelie
Published: April 2015

This chapter explores the practice of combining ubiquitous computing—information in everyday objects—with the approach of calm technology – designing ambient, intriguing presentations of information. Borrowing from these two approaches, we can define a more faceted path, imbuing physical objects and environments with data about their own surroundings in an aesthetic, tangible, and crucially subtle way. The chapter presents the concept of combining three sensory methods to strengthen learning in unexpected situations. One, the role of the spectacle produced through a dynamic, aesthetic object in learning and engagement. Two, providing an optional, detailed reference layer for said spectacle. Three, placing this experience in physical space. Information need not be constrained to the physical page of paper nor the digital screen (European Commission, 2004). Instead, it can flow through our daily life, finding place in subtle (Weiser & Brown, 1995), thoughtfully designed (Löwgren & Stolterman, 2004) surfaces and objects. This chapter discusses the example project, AiryLight, and how its motivation and execution exemplify the more faceted path and the three methods – abstract spectacle, layering of detail, and placement in physical space.
Bridging Product Design with Materials Properties and Processing
Authors: Bodratti Andrew M. , Cheng Chong , Alexandridis Paschalis
Published: April 2015

Innovative products improve the quality of our life and are important for the prosperity of the chemical and materials industries. This chapter introduces a product design capstone course for chemical engineering seniors at the University at Buffalo (SUNY), USA. The course encompassed the following themes: a general framework for product design and development (identify customer needs, convert needs to specifications, create ideas/concepts, select concept, formulate/test/manufacture product, intellectual property, safety, environmental, marketing and financial considerations); and (nano)structure-property relations that guide the search for materials (typically mixtures, blends, or composites) with particular properties. These two main themes are reinforced by case studies of successful products. The course material is integrated into nanostructured product design projects that are drawn from real-world problems. This chapter discusses the course organization, learning outcomes, teaching techniques, assignments, assessment, and student feedback. Throughout this product design course, students received significant exposure to real materials development problems and strategies.
The Interdisciplinary, Project-Based Infrastructure Degradation Curriculum at Worcester Polytechnic Institute
Authors: Sakulich Aaron , El-Korchi Tahar , Sisson Jr. Richard D.
Published: April 2015

In 2014, a new graduate-level course on infrastructure degradation was offered jointly by the departments of Mechanical Engineering and Civil and Environmental Engineering at Worcester Polytechnic Institute (WPI), USA. Over the course of the fourteen-week graduate term, seven professors from both departments offered lectures on their particular area of expertise. Together with conventional homework assignments, the course incorporated a multidisciplinary project aspect where students were divided into teams and assigned an infrastructure system. The students prepared detailed presentations on a specific aspect of the degradation methods affecting their infrastructure system. These presentations culminated in the first ever WPI Degradation Symposium, in which each student team presented a poster based on their research. This chapter outlined the motivation behind, experience with, and lessons learned from this course, which may serve as a model in corrosion education as such issues become more important with the continuing decay of the worldwide built environment.
Applying a Coherent Academy Training Structure to Vertically Integrate Learning, Teaching and Personal Development in Materials Science and Engineering
Authors: Mabbett Ian
Published: April 2015

An innovative academy structure has been applied to materials education in Swansea University, UK. The Materials Academy has multiple levels and layers, from the basic outreach and public engagement required to attract new through to doctoral training. The academy offers multiple paths for progress to all levels. With a diverse mix of talent in the participants, a range of backgrounds and experiences must be catered for in the learning environment, with teaching cycles continuously evaluated to ensure they are appropriate. From the earliest stages of engagement with the academy, learning is student led and industry demand driven. The aim is to fill skills gaps to create an employable workforce for the materials science and engineering industry and contribute positively to economic growth. This chapter described the approach taken at Swansea University, the driving force behind it, explained the features of each stage and interaction of the levels.
Innovative Instructional Strategies for Teaching Materials Science in Engineering
Authors: Ozturk Fahrettin , Deveci Tanju , Gunister Ebru , Simmons Rodney J.
Published: April 2015

Advancements in materials production and materials science education accelerate innovations in many engineering fields. Therefore, strong Materials Science education is extremely important for quality part development and efficient designs. Comfort, safety, and cost requirements can be met utilizing technology and knowledge base advancements. This chapter firstly introduces the contents of a more contemporary materials science education curriculum, and advanced content-related laboratory applications. The applicability of incorporating such content in the current curriculum and number of semester hours necessary to teach such a course are discussed. Finally, it explains the role that engineering educators have in preparing students to develop designs that add to the “triple bottom line” which considers costs in economic, social, and environmental terms. Successful Materials Science education helps technological development and increases innovations. This chapter is significant for its detailed discussion on the shortcomings of current Materials Science education and its recommendations of effective teaching strategies.
Virtual Environments in Materials Science and Engineering
Authors: Vergara D. , Lorenzo M. , Rubio M.P.
Published: April 2015

The use of virtual resources in university teaching is becoming a key issue, especially in engineering degrees where novel virtual environments are being developed. This chapter described a study on the opinions of engineering students with regard to the use of diverse virtual applications in subjects related to Materials Science and Engineering. From 2011 to 2014, engineering students of several universities and diverse nationalities were surveyed regarding their views on using virtual environments in learning. The results presented in this chapter showed that students gave great importance to the use of virtual resources in university teaching but, at the same time, they also considered the presence of the teacher in the classroom to be very essential. The findings also provided the timetable distribution of topics that, according to the students' opinion, should be considered in the subjects of Materials Science, such as master classes, problem solving classes, practical classes in both real and virtual laboratories.
Artificial Intelligence Methods and Their Applications in Civil Engineering
Authors: Martínez-Barrera Gonzalo , Gencel Osman , Beycioglu Ahmet , Subaşı Serkan , González-Rivas Nelly
Published: April 2015

Simulation of material properties generally involves the development of a mathematical model derived from experimental data. In structural mechanics and construction materials contexts, recent experiments have reported that fuzzy logic (FL), artificial neural networks (ANNs), genetic algorithm (GA), and fuzzy genetic (FG) may offer a promising alternative. They are known as artificial intelligence (AI). In civil engineering, AI methods have been extensively used in the fields of civil engineering applications such as construction management, building materials, hydraulic, optimization, geotechnical and transportation engineering. Many studies have examined the applicability of AI methods to estimate concrete properties. This chapter described the principles of FL methods that can be taught to engineering students through MATLAB graphical user interface carried out in a postgraduate course on Applications of Artificial Intelligence in Engineering, discussed the application of Mamdani type in concrete technology and highlighted key studies related to the usability of FL in concrete technology.
The Role of Digital Libraries in Teaching Materials Science and Engineering
Authors: Silva Arlindo , Infante Virginia
Published: April 2015

Nowadays, the number of commercially available materials is growing steadily. Technical information on materials resides in digital libraries that complement classical Materials Science and Engineering (MSE) textbooks. Information on materials in the form of databases of material properties can elaborate on the science and engineering fundamentals explained in textbooks with real data about current materials. Hence digital libraries can become a learning tool to support teaching of science and engineering fundamentals. This chapter described two courses offered for the Mechanical Engineering degree at Instituto Superior Tecnico, Portugal, namely Materials Science and Materials in Engineering. The Materials Science course uses the traditional textbooks and a bottom-up approach. In the Materials in Engineering course, the CES EduPack database was introduced to support a design-led approach. This chapter showed that the teaching of Materials Science with databases should be encouraged and described a successful experience with teaching Materials in Engineering using digital libraries.
Interdisciplinary Course Development in Nanostructured Materials Science and Engineering
Authors: Roberts Kenneth L.
Published: April 2015

Modern industrial processes are presently adapting to the use of multiscale production techniques where consumer products can be made at the mesoscale and also approaching atomic, or the nanoscale level. Coupled with the fact that classical Science, Technology, Engineering and Mathematics (STEM) education typically does not address nanoscale science and engineering topics in most technical courses, this condition could potentially leave countless STEM students around the world relatively unprepared for the 21st century marketplace. This chapter focused on the development of the nanostructured materials science and engineering discipline from the most recent research and development topics to the integration of this information internationally into the technical classroom. The chapter presented future work on the adaption of the previous research and educational work on this topic at the College of Engineering at King Faisal University in Saudi Arabia and suggestions were offered for successful new nanoscale science and engineering course development.
Integrating Sustainable Engineering Principles in Material Science Engineering Education
Authors: Mainali Bandita , Petrolito Joe , Russell John , Ionescu Daniela , Al Abadi Haider
Published: April 2015

The increasing demands on earth's resources require the need for engineering disciplines to address the limitations of materials and energy as well as the need to reduce waste production. This requirement is particularly acute for material science engineers as their work has a lasting impact on our future sustainability. Recent developments and innovations in material science can be useful tools for achieving sustainable development, provided material science engineers are aware of the issues. They should be particularly aware of global sustainability challenges, and should be able to understand how they can contribute to the solutions of these problems. Therefore, this chapter discusses how sustainable engineering principles can be introduced into material science education. It also discusses the curriculum for the subject Sustainable Infrastructure that is offered at La Trobe University in Victoria (Australia) for senior Civil Engineering students.
Materials as a Bridge between Science, Engineering, and Design
Authors: Silva Arlindo
Published: April 2015

This chapter explores the idea of using the topic of materials as a bridge between three fields of knowledge: materials science, mechanical engineering and product design. It discusses ways in which the teaching of materials to diverse student audiences can be enhanced. For example, how a course is to be taught by materials scientists to product designers where the instructor has a fundamentally different notion of what materials are compared to the students' perception of what materials are and how they can be used in their future profession. A broader vision of what the materials discipline means needs to be acknowledged in order to build a common materials education thread. The chapter presents the visions of three common materials user groups – materials scientists, mechanical engineers, and product designers – and highlights the differences and similarities amongst them in the context of developing further materials knowledge and education.
Successes in the Development of an Arabian Gulf Materials Program
Authors: Palmer Bruce. R. , Abdeen Dana , Khalfaoui Walid , Al Jassem Nasser , Mishra Brajendra , Lee Eunkyung , Olson David LeRoy
Published: April 2015

A materials research program was established to identify new corrosion resistant stainless steel alloys for the oil and gas industry. One important goal of this work was developing professionals to address the critical materials issues in the Arabian Gulf Region. This chapter reports the results of these efforts. Development of research professionals involved a multifaceted approach. One key element involved laboratory work to develop the critical research tools required in this area. The effort also included development of important course content for both undergraduate and graduate-level materials education. The research in this program stems from a collaboration between Texas A&M University at Qatar and the Colorado School of Mines. Collaboration provided many of the important tools required for this new Middle Eastern education initiative. The present chapter describes the challenges that were addressed in order to develop crucial new materials research and education capabilities in this major petroleum producing region.
Setting up a Learning Environment in an Interdisciplinary Professional Collaboration
Authors: Legland Elin
Published: April 2015

Collaboration between universities, industries and other professional societies enables students to enter interdisciplinary learning environments through joint research. Stakeholders can attain their objectives through collaboration and a range of competitive advantages in own business sector. From an economic perspective, the fruits of research and development such as intelligent property are motivators for collaboration. From an educational perspective, this three party collaboration provides opportunities for situated learning that link theoretical studies with practical research work. This chapter discusses the contributions to the learning environment from collaboration between education, research and industry, and their impact on the professional growth of engineering graduates in the field of Material Science. Through self-reflection on experience, author argued that by combining theoretical knowledge from university education and research with practical skills and experience gained from the industry, students develop individual empowerment and bring future business advantages to the industries where they would later work.
Altered Connexin 43 Expression Underlies Age-Dependent Decrease of Regulatory T Cell Suppressor Function in Nonobese Diabetic Mice
Authors: Kuczma Michal , Wang Cong-Yi , Ignatowicz Leszek , Gourdie Robert , Kraj Piotr
Published: April 2015

Type 1 diabetes is one of the most extensively studied autoimmune diseases, but the cellular and molecular mechanisms leading to T cell–mediated destruction of insulin-producing β cells are still not well understood. In this study, we show that regulatory T cells (Tregs) in NOD mice undergo age-dependent loss of suppressor functions exacerbated by the decreased ability of activated effector T cells to upregulate Foxp3 and generate Tregs in the peripheral organs. This age-dependent loss is associated with reduced intercellular communication mediated by gap junctions, which is caused by impaired upregulation and decreased expression of connexin 43. Regulatory functions can be corrected, even in T cells isolated from aged, diabetic mice, by a synergistic activity of retinoic acid, TGF-β, and IL-2, which enhance connexin 43 and Foxp3 expression in Tregs and restore the ability of conventional CD4+ T cells to upregulate Foxp3 and generate peripherally derived Tregs. Moreover, we demonstrate that suppression mediated by Tregs from diabetic mice is enhanced by a novel reagent, which facilitates gap junction aggregation. In summary, our report identifies gap junction–mediated intercellular communication as an important component of the Treg suppression mechanism compromised in NOD mice and suggests how Treg mediated immune regulation can be improved.
Proinflammatory Proteins S100A8/S100A9 Activate NK Cells via Interaction with RAGE
Authors: Narumi Kenta , Miyakawa Reina , Ueda Ryosuke , Hashimoto Hisayoshi , Yamamoto Yuki , Yoshida Teruhiko , Aoki Kazunori
Published: April 2015

S100A8/A9, a proinflammatory protein, is upregulated in inflammatory diseases, and also has a tumor-promoting activity by the recruitment of myeloid cells and tumor cell invasion. However, whether the expression of S100A8/A9 in tumors predicts a good or poor prognosis is controversial in the clinical setting. In this study, to clarify the in vivo role of S100A8/A9 in the tumor microenvironment, we s.c. inoculated Pan02 cells stably expressing S100A8 and S100A9 proteins (Pan02-S100A8/A9) in syngeneic C57BL/6 mice. Unexpectedly, after small tumor nodules were once established, they rapidly disappeared. Flow cytometry showed that the number of NK cells in the tumors was increased, and an administration of anti-asialoGM1 Ab for NK cell depletion promoted the growth of Pan02-S100A8/A9 s.c. tumors. Although the S100A8/A9 proteins alone did not change the IFN-γ expression of NK cells in vitro, a coculture with Pan02 cells, which express Rae-1, induced IFN-γ production, and Pan02-S100A8/A9 cells further increased the number of IFN-γ+ NK cells, suggesting that S100A8/A9 enhanced the NK group 2D ligand-mediated intracellular activation pathway in NK cells. We then examined whether NK cell activation by S100A8/A9 was via their binding to receptor of advanced glycation end product (RAGE) by using the inhibitors. RAGE antagonistic peptide and anti-RAGE Ab inhibited the IFN-γ production of NK cells induced by S100A8/A9 proteins, and an administration of FPS-ZM1, a RAGE inhibitor, significantly enhanced the in vivo growth of Pan02-S100A8/A9 tumors. We thus found a novel activation mechanism of NK cells via S100A8/A9–RAGE signaling, which may open a novel perspective on the in vivo interaction between inflammation and innate immunity.
CD14++CD16+ Monocytes Are Enriched by Glucocorticoid Treatment and Are Functionally Attenuated in Driving Effector T Cell Responses
Authors: Liu Baoying , Dhanda Ashwin , Hirani Sima , Williams Emily L. , Sen H. Nida , Martinez Estrada Fernando , Ling Diamond , Thompson Ian , Casady Megan , Li Zhiyu , Si Han , Tucker William , Wei Lai , Jawad Shayma , Sura Amol , Dailey Jennifer , Hannes Susan , Chen Ping , Chien Jason L. , Gordon Siamon , Lee Richard W. J. , Nussenblatt Robert B.
Published: April 2015

Human peripheral monocytes have been categorized into three subsets based on differential expression levels of CD14 and CD16. However, the factors that influence the distribution of monocyte subsets and the roles that each subset plays in autoimmunity are not well studied. In this study, we show that circulating monocytes from patients with autoimmune uveitis exhibit a skewed phenotype toward intermediate CD14++CD16+ cells, and that this is associated with glucocorticoid therapy. We further demonstrate that CD14++CD16+ monocytes from patients and healthy control donors share a similar cell-surface marker and gene expression profile. Comparison of the effects of intermediate CD14++CD16+ monocytes with classical CD14++CD16− and nonclassical CD14+CD16++ monocytes revealed that the intermediate CD14++CD16+ subset had an attenuated capacity to promote both naive CD4+ T cell proliferation and polarization into a Th1 phenotype, and memory CD4+ T cell proliferation and IL-17 expression. Furthermore, CD14++CD16+ cells inhibit CD4+ T cell proliferation induced by other monocyte subsets and enhance CD4+ T regulatory cell IL-10 expression. These data demonstrate the impact of glucocorticoids on monocyte phenotype in the context of autoimmune disease and the differential effects of monocyte subsets on effector T cell responses.
B7H6-Specific Bispecific T Cell Engagers Lead to Tumor Elimination and Host Antitumor Immunity
Authors: Wu Ming-Ru , Zhang Tong , Gacerez Albert T. , Coupet Tiffany A. , DeMars Leslie R. , Sentman Charles L.
Published: April 2015

Substantial evidence showed that T cells are the key effectors in immune-mediated tumor eradication; however, most T cells do not exhibit antitumor specificity. In this study, a bispecific T cell engager (BiTE) approach was used to direct T cells to recognize B7H6+ tumor cells. B7H6 is a specific ligand for the NK cell–activating receptor NKp30. B7H6 is expressed on various types of primary human tumors, including leukemia, lymphoma, and gastrointestinal stromal tumors, but it is not constitutively expressed on normal tissues. Data from this study showed that B7H6-specific BiTEs direct T cells to mediate cellular cytotoxicity and IFN-γ secretion upon coculturing with B7H6+ tumors. Furthermore, B7H6-specific BiTE exhibited no self-reactivity to proinflammatory monocytes. In vivo, B7H6-specific BiTE greatly enhanced the survival benefit of RMA/B7H6 lymphoma-bearing mice through perforin and IFN-γ effector mechanisms. In addition, long-term survivor mice were protected against an RMA lymphoma tumor rechallenge. The B7H6-specific BiTE therapy also decreased tumor burden in murine melanoma and ovarian cancer models. In conclusion, B7H6-specific BiTE activates host T cells and has the potential to treat various B7H6+ hematological and solid tumors.
Viremic HIV Controllers Exhibit High Plasmacytoid Dendritic Cell–Reactive Opsonophagocytic IgG Antibody Responses against HIV-1 p24 Associated with Greater Antibody Isotype Diversification
Authors: Tjiam M. Christian , Taylor James P. A. , Morshidi Mazmah A. , Sariputra Lucy , Burrows Sally , Martin Jeffrey N. , Deeks Steven G. , Tan Dino B. A. , Lee Silvia , Fernandez Sonia , French Martyn A.
Published: April 2015

Identifying the mechanisms of natural control of HIV-1 infection could lead to novel approaches to prevent or cure HIV infection. Several studies have associated natural control of HIV-1 infection with IgG Abs against HIV-1 Gag proteins (e.g., p24) and/or production of IgG2 Abs against HIV-1 proteins. These Abs likely exert their effect by activating antiviral effector cell responses rather than virus neutralization. We hypothesized that an opsonophagocytic IgG Ab response against HIV-1 p24 that activates plasmacytoid dendritic cells (pDCs) through FcγRIIa would be associated with control of HIV and that this would be enhanced by Ab isotype diversification. Using the Gen2.2 pDC cell line, we demonstrated that pDC-reactive opsonophagocytic IgG Ab responses against HIV-1 p24 were higher in HIV controllers (HIV RNA < 2000 copies/ml) than noncontrollers (HIV RNA > 10,000 copies/ml), particularly in controllers with low but detectable viremia (HIV RNA 75–2000 copies/ml). Opsonophagocytic Ab responses correlated with plasma levels of IgG1 and IgG2 anti-HIV-1 p24 and, notably, correlated inversely with plasma HIV RNA levels in viremic HIV patients. Phagocytosis of these Abs was mediated via FcγRIIa. Isotype diversification (toward IgG2) was greatest in HIV controllers, and depletion of IgG2 from Ig preparations indicated that IgG2 Abs to HIV-1 p24 do not enhance phagocytosis, suggesting that they enhance other aspects of Ab function, such as Ag opsonization. Our findings emulate those for pDC-reactive opsonophagocytic Ab responses against coxsackie, picorna, and influenza viruses and demonstrate a previously undefined immune correlate of HIV-1 control that may be relevant to HIV vaccine development.
The Thrombin-Derived Host Defense Peptide GKY25 Inhibits Endotoxin-Induced Responses through Interactions with Lipopolysaccharide and Macrophages/Monocytes
Authors: Hansen Finja C. , Kalle-Brune Martina , van der Plas Mariena J. A. , Strömdahl Ann-Charlotte , Malmsten Martin , Mörgelin Matthias , Schmidtchen Artur
Published: April 2015

Host defense peptides have recently gained much interest as novel anti-infectives owing to their ability to kill bacteria and simultaneously modulate host cell responses. The cationic host defense peptide GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), derived from the C terminus of human thrombin, inhibits proinflammatory responses in vitro and in vivo, but the mode of action is unclear. In this study, we show that GKY25, apart from binding bacterial LPS, also interacts directly with monocytes and macrophages in vitro, ex vivo, and in vivo. Moreover, GKY25 inhibits TLR4- and TLR2-induced NF-κB activation in response to several microbe-derived agonists. Furthermore, GKY25 reduces LPS-induced phosphorylation of MAPKs p38α and JNK1/2/3. FACS and electron microscopy analyses showed that GKY25 interferes with TLR4/myeloid differentiation protein-2 dimerization. The results demonstrate a previously undisclosed activity of the host defense peptide GKY25, based on combined LPS and cell interactions leading to inhibition of TLR4 dimerization and subsequent reduction of NF-κB activity and proinflammatory cytokine production in monocytes and macrophages.
miR-155 Deficiency Ameliorates Autoimmune Inflammation of Systemic Lupus Erythematosus by Targeting S1pr1 in Faslpr/lpr Mice
Authors: Xin Qian , Li Jiangxia , Dang Jie , Bian Xianli , Shan Shan , Yuan Jupeng , Qian Yanyan , Liu Zhaojian , Liu Guangyi , Yuan Qianqian , Liu Na , Ma Xiaochun , Gao Fei , Gong Yaoqin , Liu Qiji
Published: April 2015

MicroRNA-155 (miR-155) was previously found involved in the development of systemic lupus erythematosus (SLE) and other autoimmune diseases and the inflammatory response; however, the detailed mechanism of miR-155 in SLE is not fully understood. To explore the in vivo role of miR-155 in the pathogenesis of SLE, miR-155–deficient Faslpr/lpr (miR-155−/−Faslpr/lpr) mice were obtained by crossing miR-155−/− and Faslpr/lpr mice. Clinical SLE features such as glomerulonephritis, autoantibody levels, and immune system cell populations were compared between miR-155−/−Faslpr/lpr and Faslpr/lpr mice. Microarray analysis, RT-PCR, Western blot, and luciferase reporter gene assay were used to identify the target gene of miR-155. miR-155−/−Faslpr/lpr mice showed milder SLE clinical features than did Faslpr/lprmice. As compared with Faslpr/lpr mice, miR-155−/−Faslpr/lpr mice showed less deposition of total IgA, IgM, and IgG and less infiltration of inflammatory cells in the kidney. Moreover, the serum levels of IL-4 and IL-17a, secreted by Th2 and Th17 cells, were lower in miR-155−/−Faslpr/lpr than Faslpr/lpr mice; the CD4+/CD8+ T cell ratio was restored in miR-155−/−Faslpr/lpr mice as well. Sphingosine-1-phosphate receptor 1 (S1PR1) was found as a new target gene of miR-155 by in vitro and in vivo studies; its expression was decreased in SLE patients and Faslpr/lpr mice. miR-155−/−Faslpr/lpr mice are resistant to the development of SLE by the regulation of the target gene S1pr1. miR-155 might be a new target for therapeutic intervention in SLE.
Pulmonary Alveolar Macrophages Contribute to the Premetastatic Niche by Suppressing Antitumor T Cell Responses in the Lungs
Authors: Sharma Sharad K. , Chintala Navin K. , Vadrevu Surya Kumari , Patel Jalpa , Karbowniczek Magdalena , Markiewski Maciej M.
Published: April 2015

In contrast to tumor-associated macrophages, myeloid-derived suppressor cells, or inflammatory monocytes, functions of tissue resident macrophages, including alveolar macrophages (AM), in cancer were not well studied. Using a mouse model of breast cancer, we show that AM promote cancer metastasis to the lungs by suppressing antitumor T cells in this organ. AM accumulated in the premetastatic lungs through complement C5a receptor–mediated proliferation but not through recruitment from the circulation. AM preconditioned by breast tumors inhibited Th1 and favored generation of Th2 cells that had lower tumoricidal activity than Th1 cells. In addition, AM reduced the number and maturation of lung dendritic cells by regulating TGF-β in the lung environment. Depletion of AM reversed immunosuppression imposed by these cells and strengthened local Th1 responses, which significantly reduced lung metastatic burden. C5a receptor deficiency, which also lessens myeloid-derived suppressor cells in the premetastatic niche, synergized with the depletion of AM in preventing metastasis, leading to protection of mice from lung metastases. This study identifies AM as a new component of the premetastatic niche, which is harnessed by tumors to impose immunosuppression, and as a new target for cancer immunotherapies to eliminate or reduce metastasis. Because the lungs are the most common target for hematogenous metastasis, this research offers a plausible explanation for susceptibility of the lungs to cancer metastasis.
Early Effector Cells Survive the Contraction Phase in Malaria Infection and Generate Both Central and Effector Memory T Cells
Authors: Opata Michael M. , Carpio Victor H. , Ibitokou Samad A. , Dillon Brian E. , Obiero Joshua M. , Stephens Robin
Published: April 2015

CD4 T cells orchestrate immunity against blood-stage malaria. However, a major challenge in designing vaccines to the disease is poor understanding of the requirements for the generation of protective memory T cells (Tmem) from responding effector T cells (Teff) in chronic parasite infection. In this study, we use a transgenic mouse model with T cells specific for the merozoite surface protein (MSP)-1 of Plasmodium chabaudi to show that activated T cells generate three distinct Teff subsets with progressive activation phenotypes. The earliest observed Teff subsets (CD127−CD62LhiCD27+) are less divided than CD62Llo Teff and express memory genes. Intermediate (CD62LloCD27+) effector subsets include the most multicytokine-producing T cells, whereas fully activated (CD62LloCD27−) late effector cells have a terminal Teff phenotype (PD-1+, Fashi, AnnexinV+). We show that although IL-2 promotes expansion, it actually slows terminal effector differentiation. Using adoptive transfer, we show that only early Teff survive the contraction phase and generate the terminal late Teff subsets, whereas in uninfected recipients, they become both central and effector Tmem. Furthermore, we show that progression toward full Teff activation is promoted by increased duration of infection, which in the long-term promotes Tem differentiation. Therefore, we have defined markers of progressive activation of CD4 Teff at the peak of malaria infection, including a subset that survives the contraction phase to make Tmem, and show that Ag and cytokine levels during CD4 T cell expansion influence the proportion of activated cells that can survive contraction and generate memory in malaria infection.
MijnBorne2030: evaluatie van een democratisch experiment
Authors: Denters Bas , Klok Pieter-Jan
Published: April 2015

MyBorne2030: evaluation of a democratic experiment

This article is about one of the experiments in local democratic renewal: MyBorne2030 (in Dutch ‘MijnBorne2030’). The aim of the project was to develop a communal vision for Borne (a relatively small suburban municipality of 20.000 inhabitants in the East of the Netherlands) for the year 2030. A steering committee of 20 local organizations has worked out four scenarios on the basis of three building stones: an identity study, a research of societal trends and the formulation of ambitions. These four scenarios have been submitted to the citizens of Borne in a referendum. The scenario that has received the most votes (‘Dynamic villages’) is further elaborated in a new vison for the future called MyBorne2030. Institutionally the decision-making process in Borne can be described as a mixture of participative (deliberative), associative and direct (plebiscitary) democracy. The authors conclude that it was a successful experiment, that has produced broad support for the vision of Borne for the future and a solid basis for the implementation of this vision. Participants (as well as non-participants) think this approach can be repeated not only in Borne, but also in other municipalities. The authors add that this could also be the case for the level above of cooperating municipalities.
Dichotoom in dialoog? Lokale referenda in Nederland
Authors: van der Krieken Koen , de Graaf Laurens
Published: April 2015

Dichotomous in dialogue? Local referenda in the Netherlands

This article is about local referenda in the Netherlands. Based on extensive empirical research the authors make clear how the local referendum in the Dutch democracy has developed not only in time and practice, but also how we can interpret the referendum theoretically. They show how in scientific literature, but also in practice, they are still looking for the meaning of the local referendum for Dutch local democracy. The authors also show that the practice of Dutch local referenda is searching, varied and in continuous development. Since 1906 193 local referenda are organized in the Netherlands. By far most referenda took place after the nineties of the last century. Local referenda are a local democratic ‘domain’, that will be explored in the Netherlands in the coming years. Last year a lot of attention has been given to the (local) referendum in the domain of legislation. The process of legislation has not been finished yet. The authors believe this offers an unique opportunity to share the available knowledge and experience about referenda and debate the adequate filling in and anchoring of the (local) referendum. This is a task for scientists, administrators and politicians alike.
Placental Mesenchymal Stromal Cells Rescue Ambulation in Ovine Myelomeningocele
Authors: Wang Aijun , Brown Erin G. , Lankford Lee , Keller Benjamin A. , Pivetti Christopher D. , Sitkin Nicole A. , Beattie Michael S. , Bresnahan Jacqueline C. , Farmer Diana L.
Published: April 2015

Myelomeningocele (MMC)—commonly known as spina bifida—is a congenital birth defect that causes lifelong paralysis, incontinence, musculoskeletal deformities, and severe cognitive disabilities. The recent landmark Management of Myelomeningocele Study (MOMS) demonstrated for the first time in humans that in utero surgical repair of the MMC defect improves lower limb motor function, suggesting a capacity for improved neurologic outcomes in this disorder. However, functional recovery was incomplete, and 58% of the treated children were unable to walk independently at 30 months of age. In the present study, we demonstrate that using early gestation human placenta-derived mesenchymal stromal cells (PMSCs) to augment in utero repair of MMC results in significant and consistent improvement in neurologic function at birth in the rigorous fetal ovine model of MMC. In vitro, human PMSCs express characteristic MSC markers and trilineage differentiation potential. Protein array assays and enzyme-linked immunosorbent assay show that PMSCs secrete a variety of immunomodulatory and angiogenic cytokines. Compared with adult bone marrow MSCs, PMSCs secrete significantly higher levels of brain-derived neurotrophic factor and hepatocyte growth factor, both of which have known neuroprotective capabilities. In vivo, functional and histopathologic analysis demonstrated that human PMSCs mediate a significant, clinically relevant improvement in motor function in MMC lambs and increase the preservation of large neurons within the spinal cord. These preclinical results in the well-established fetal ovine model of MMC provide promising early support for translating in utero stem cell therapy for MMC into clinical application for patients.

Significance

This study presents placenta-derived mesenchymal stromal cell (PMSC) treatment as a potential therapy for myelomeningocele (MMC). Application of PMSCs can augment current in utero surgical repair in the well-established and rigorously applied fetal lamb model of MMC. Treatment with human PMSCs significantly and dramatically improved neurologic function and preserved spinal cord neuron density in experimental animals. Sixty-seven percent of the PMSC-treated lambs were able to ambulate independently, with two exhibiting no motor deficits whatsoever. In contrast, none of the lambs treated with the vehicle alone were capable of ambulation. The locomotor rescue demonstrated in PMSC-treated lambs indicates great promise for future clinical trials to improve paralysis in children afflicted with MMC.
The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer
Authors: Wang Eric , Kawaoka Shinpei , Roe Jae-Seok , Shi Junwei , Hohmann Anja F , Xu Yali , Bhagwat Anand S , Suzuki Yutaka , Kinney Justin B , Vakoc Christopher R
Published: April 2015

Most mammalian transcription factors (TFs) and cofactors occupy thousands of genomic sites and modulate the expression of large gene networks to implement their biological functions. In this study, we describe an exception to this paradigm. TRIM33 is identified here as a lineage dependency in B cell neoplasms and is shown to perform this essential function by associating with a single cis element. ChIP-seq analysis of TRIM33 in murine B cell leukemia revealed a preferential association with two lineage-specific enhancers that harbor an exceptional density of motifs recognized by the PU.1 TF. TRIM33 is recruited to these elements by PU.1, yet acts to antagonize PU.1 function. One of the PU.1/TRIM33 co-occupied enhancers is upstream of the pro-apoptotic gene Bim, and deleting this enhancer renders TRIM33 dispensable for leukemia cell survival. These findings reveal an essential role for TRIM33 in preventing apoptosis in B lymphoblastic leukemia by interfering with enhancer-mediated Bim activation.