3D bioprinting: improving in vitro models of metastasis with heterogeneous tumor microenvironments

Directory of Open Access Journals (Sweden)

Jacob L. Albritton

2017-01-01

Full Text Available Even with many advances in treatment over the past decades, cancer still remains a leading cause of death worldwide. Despite the recognized relationship between metastasis and increased mortality rate, surprisingly little is known about the exact mechanism of metastatic progression. Currently available in vitro models cannot replicate the three-dimensionality and heterogeneity of the tumor microenvironment sufficiently to recapitulate many of the known characteristics of tumors in vivo. Our understanding of metastatic progression would thus be boosted by the development of in vitro models that could more completely capture the salient features of cancer biology. Bioengineering groups have been working for over two decades to create in vitro microenvironments for application in regenerative medicine and tissue engineering. Over this time, advances in 3D printing technology and biomaterials research have jointly led to the creation of 3D bioprinting, which has improved our ability to develop in vitro models with complexity approaching that of the in vivo tumor microenvironment. In this Review, we give an overview of 3D bioprinting methods developed for tissue engineering, which can be directly applied to constructing in vitro models of heterogeneous tumor microenvironments. We discuss considerations and limitations associated with 3D printing and highlight how these advances could be harnessed to better model metastasis and potentially guide the development of anti-cancer strategies.

3D bioprinting: improving in vitro models of metastasis with heterogeneous tumor microenvironments.

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Albritton, Jacob L; Miller, Jordan S

2017-01-01

Even with many advances in treatment over the past decades, cancer still remains a leading cause of death worldwide. Despite the recognized relationship between metastasis and increased mortality rate, surprisingly little is known about the exact mechanism of metastatic progression. Currently available in vitro models cannot replicate the three-dimensionality and heterogeneity of the tumor microenvironment sufficiently to recapitulate many of the known characteristics of tumors in vivo Our understanding of metastatic progression would thus be boosted by the development of in vitro models that could more completely capture the salient features of cancer biology. Bioengineering groups have been working for over two decades to create in vitro microenvironments for application in regenerative medicine and tissue engineering. Over this time, advances in 3D printing technology and biomaterials research have jointly led to the creation of 3D bioprinting, which has improved our ability to develop in vitro models with complexity approaching that of the in vivo tumor microenvironment. In this Review, we give an overview of 3D bioprinting methods developed for tissue engineering, which can be directly applied to constructing in vitro models of heterogeneous tumor microenvironments. We discuss considerations and limitations associated with 3D printing and highlight how these advances could be harnessed to better model metastasis and potentially guide the development of anti-cancer strategies. © 2017. Published by The Company of Biologists Ltd.

Tunable Collagen I Hydrogels for Engineered Physiological Tissue Micro-Environments

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Antoine, Elizabeth E.; Vlachos, Pavlos P.; Rylander, Marissa N.

2015-01-01

Collagen I hydrogels are commonly used to mimic the extracellular matrix (ECM) for tissue engineering applications. However, the ability to design collagen I hydrogels similar to the properties of physiological tissues has been elusive. This is primarily due to the lack of quantitative correlations between multiple fabrication parameters and resulting material properties. This study aims to enable informed design and fabrication of collagen hydrogels in order to reliably and reproducibly mimic a variety of soft tissues. We developed empirical predictive models relating fabrication parameters with material and transport properties. These models were obtained through extensive experimental characterization of these properties, which include compression modulus, pore and fiber diameter, and diffusivity. Fabrication parameters were varied within biologically relevant ranges and included collagen concentration, polymerization pH, and polymerization temperature. The data obtained from this study elucidates previously unknown fabrication-property relationships, while the resulting equations facilitate informed a priori design of collagen hydrogels with prescribed properties. By enabling hydrogel fabrication by design, this study has the potential to greatly enhance the utility and relevance of collagen hydrogels in order to develop physiological tissue microenvironments for a wide range of tissue engineering applications. PMID:25822731

Neuro-immune modulation of the thymus microenvironment (review).

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Mignini, Fiorenzo; Sabbatini, Maurizio; Mattioli, Laura; Cosenza, Monica; Artico, Marco; Cavallotti, Carlo

2014-06-01

The thymus is the primary site for T-cell lympho-poiesis. Its function includes the maturation and selection of antigen specific T cells and selective release of these cells to the periphery. These highly complex processes require precise parenchymal organization and compartmentation where a plethora of signalling pathways occur, performing strict control on the maturation and selection processes of T lymphocytes. In this review, the main morphological characteristics of the thymus microenvironment, with particular emphasis on nerve fibers and neuropeptides were assessed, as both are responsible for neuro-immune‑modulation functions. Among several neurotransmitters that affect thymus function, we highlight the dopaminergic system as only recently has its importance on thymus function and lymphocyte physiology come to light.

Engineering Enriched Microenvironments with Gradients of Platelet Lysate in Hydrogel Fibers.

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Santo, Vítor E; Babo, Pedro; Amador, Miguel; Correia, Cláudia; Cunha, Bárbara; Coutinho, Daniela F; Neves, Nuno M; Mano, João F; Reis, Rui L; Gomes, Manuela E

2016-06-13

Gradients of physical and chemical cues are characteristic of specific tissue microenvironments and contribute toward morphogenesis and tissue regeneration upon injury. Recent advances on microfluidics and hydrogel manipulation raised the possibility of generating biomimetic biomaterials enriched with bioactive factors and encapsulating cells following designs specifically tailored for a target application. The novelty of this work relies on the combination of methacrylated gellan gum (MeGG) with platelet lysate (PL), aiming to generate novel advanced 3D PL-enriched photo-cross-linkable hydrogels and overcoming the lack of adhesion sites provided by the native MeGG hydrogels. This combination takes advantage of the availability, enriched growth factor composition, and potential autologous application of PL while simultaneously preserving the ability provided by MeGG to tailor mechanical properties, protein release kinetics, and shape of the construct according to the desired goal. Incorporation of PL in the hydrogels significantly improved cellular adhesion and viability in the constructs. The use of microfluidic tools allowed the design of a fiber-like hydrogel incorporating a gradient of PL along the length of the fiber. These spatial protein gradients led to the viability and cell number gradients caused by maintenance of human umbilical vein endothelial cells (HUVECs) survival in the fibers toward the PL-enriched sections in comparison with the nonloaded MeGG sections of the fibers. Altogether, we propose a proof of concept strategy to design a PL gradient biomaterial with potential in tissue engineering approaches and analysis of cell-microenvironment interactions.

The intestinal microenvironment in sepsis.

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Fay, Katherine T; Ford, Mandy L; Coopersmith, Craig M

2017-10-01

The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients. Published by Elsevier B.V.

A Review of Hyaluronic Acid and Hyaluronic Acid-based Hydrogels for Vocal Fold Tissue Engineering.

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Walimbe, Tanaya; Panitch, Alyssa; Sivasankar, Preeti M

2017-07-01

Vocal fold scarring is a common cause of dysphonia. Current treatments involving vocal fold augmentation do not yield satisfactory outcomes in the long term. Tissue engineering and regenerative medicine offer an attractive treatment option for vocal fold scarring, with the aim to restore the native extracellular matrix microenvironment and biomechanical properties of the vocal folds by inhibiting progression of scarring and thus leading to restoration of normal vocal function. Hyaluronic acid is a bioactive glycosaminoglycan responsible for maintaining optimum viscoelastic properties of the vocal folds and hence is widely targeted in tissue engineering applications. This review covers advances in hyaluronic acid-based vocal fold tissue engineering and regeneration strategies. Copyright © 2017. Published by Elsevier Inc.

Engineering Review Information System

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Grems, III, Edward G. (Inventor); Henze, James E. (Inventor); Bixby, Jonathan A. (Inventor); Roberts, Mark (Inventor); Mann, Thomas (Inventor)

2015-01-01

A disciplinal engineering review computer information system and method by defining a database of disciplinal engineering review process entities for an enterprise engineering program, opening a computer supported engineering item based upon the defined disciplinal engineering review process entities, managing a review of the opened engineering item according to the defined disciplinal engineering review process entities, and closing the opened engineering item according to the opened engineering item review.

Current Advancements and Strategies in Tissue Engineering for Wound Healing: A Comprehensive Review.

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Ho, Jasmine; Walsh, Claire; Yue, Dominic; Dardik, Alan; Cheema, Umber

2017-06-01

Significance: With an aging population leading to an increase in diabetes and associated cutaneous wounds, there is a pressing clinical need to improve wound-healing therapies. Recent Advances: Tissue engineering approaches for wound healing and skin regeneration have been developed over the past few decades. A review of current literature has identified common themes and strategies that are proving successful within the field: The delivery of cells, mainly mesenchymal stem cells, within scaffolds of the native matrix is one such strategy. We overview these approaches and give insights into mechanisms that aid wound healing in different clinical scenarios. Critical Issues: We discuss the importance of the biomimetic niche, and how recapitulating elements of the native microenvironment of cells can help direct cell behavior and fate. Future Directions: It is crucial that during the continued development of tissue engineering in wound repair, there is close collaboration between tissue engineers and clinicians to maintain the translational efficacy of this approach.

Dry Eye Management: Targeting the Ocular Surface Microenvironment

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Zhang, Xiaobo; Jeyalatha M, Vimalin; Qu, Yangluowa; He, Xin; Ou, Shangkun; Bu, Jinghua; Jia, Changkai; Wang, Junqi; Wu, Han; Liu, Zuguo

2017-01-01

Dry eye can damage the ocular surface and result in mild corneal epithelial defect to blinding corneal pannus formation and squamous metaplasia. Significant progress in the treatment of dry eye has been made in the last two decades; progressing from lubricating and hydrating the ocular surface with artificial tear to stimulating tear secretion; anti-inflammation and immune regulation. With the increase in knowledge regarding the pathophysiology of dry eye, we propose in this review the concept of ocular surface microenvironment. Various components of the microenvironment contribute to the homeostasis of ocular surface. Compromise in one or more components can result in homeostasis disruption of ocular surface leading to dry eye disease. Complete evaluation of the microenvironment component changes in dry eye patients will not only lead to appropriate diagnosis, but also guide in timely and effective clinical management. Successful treatment of dry eye should be aimed to restore the homeostasis of the ocular surface microenvironment. PMID:28661456

Dry Eye Management: Targeting the Ocular Surface Microenvironment.

Science.gov (United States)

Zhang, Xiaobo; M, Vimalin Jeyalatha; Qu, Yangluowa; He, Xin; Ou, Shangkun; Bu, Jinghua; Jia, Changkai; Wang, Junqi; Wu, Han; Liu, Zuguo; Li, Wei

2017-06-29

Dry eye can damage the ocular surface and result in mild corneal epithelial defect to blinding corneal pannus formation and squamous metaplasia. Significant progress in the treatment of dry eye has been made in the last two decades; progressing from lubricating and hydrating the ocular surface with artificial tear to stimulating tear secretion; anti-inflammation and immune regulation. With the increase in knowledge regarding the pathophysiology of dry eye, we propose in this review the concept of ocular surface microenvironment. Various components of the microenvironment contribute to the homeostasis of ocular surface. Compromise in one or more components can result in homeostasis disruption of ocular surface leading to dry eye disease. Complete evaluation of the microenvironment component changes in dry eye patients will not only lead to appropriate diagnosis, but also guide in timely and effective clinical management. Successful treatment of dry eye should be aimed to restore the homeostasis of the ocular surface microenvironment.

Hydrogels for precision meniscus tissue engineering: a comprehensive review.

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Rey-Rico, Ana; Cucchiarini, Magali; Madry, Henning

The meniscus plays a pivotal role to preserve the knee joint homeostasis. Lesions to the meniscus are frequent, have a reduced ability to heal, and may induce tibiofemoral osteoarthritis. Current reconstructive therapeutic options mainly focus on the treatment of lesions in the peripheral vascularized region. In contrast, few approaches are capable of stimulating repair of damaged meniscal tissue in the central, avascular portion. Tissue engineering approaches are of high interest to repair or replace damaged meniscus tissue in this area. Hydrogel-based biomaterials are of special interest for meniscus repair as its inner part contains relatively high proportions of proteoglycans which are responsible for the viscoelastic compressive properties and hydration grade. Hydrogels exhibiting high water content and providing a specific three-dimensional (3D) microenvironment may be engineered to precisely resemble this topographical composition of the meniscal tissue. Different polymers of both natural and synthetic origins have been manipulated to produce hydrogels hosting relevant cell populations for meniscus regeneration and provide platforms for meniscus tissue replacement. So far, these compounds have been employed to design controlled delivery systems of bioactive molecules involved in meniscal reparative processes or to host genetically modified cells as a means to enhance meniscus repair. This review describes the most recent advances on the use of hydrogels as platforms for precision meniscus tissue engineering.

Engineering Technical Review Planning Briefing

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Gardner, Terrie

2012-01-01

The general topics covered in the engineering technical planning briefing are 1) overviews of NASA, Marshall Space Flight Center (MSFC), and Engineering, 2) the NASA Systems Engineering(SE) Engine and its implementation , 3) the NASA Project Life Cycle, 4) MSFC Technical Management Branch Services in relation to the SE Engine and the Project Life Cycle , 5) Technical Reviews, 6) NASA Human Factor Design Guidance , and 7) the MSFC Human Factors Team. The engineering technical review portion of the presentation is the primary focus of the overall presentation and will address the definition of a design review, execution guidance, the essential stages of a technical review, and the overall review planning life cycle. Examples of a technical review plan content, review approaches, review schedules, and the review process will be provided and discussed. The human factors portion of the presentation will focus on the NASA guidance for human factors. Human factors definition, categories, design guidance, and human factor specialist roles will be addressed. In addition, the NASA Systems Engineering Engine description, definition, and application will be reviewed as background leading into the NASA Project Life Cycle Overview and technical review planning discussion.

Engineering anisotropic biomimetic fibrocartilage microenvironment by bioprinting mesenchymal stem cells in nanoliter gel droplets.

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Gurkan, Umut A; El Assal, Rami; Yildiz, Simin E; Sung, Yuree; Trachtenberg, Alexander J; Kuo, Winston P; Demirci, Utkan

2014-07-07

Over the past decade, bioprinting has emerged as a promising patterning strategy to organize cells and extracellular components both in two and three dimensions (2D and 3D) to engineer functional tissue mimicking constructs. So far, tissue printing has neither been used for 3D patterning of mesenchymal stem cells (MSCs) in multiphase growth factor embedded 3D hydrogels nor been investigated phenotypically in terms of simultaneous differentiation into different cell types within the same micropatterned 3D tissue constructs. Accordingly, we demonstrated a biochemical gradient by bioprinting nanoliter droplets encapsulating human MSCs, bone morphogenetic protein 2 (BMP-2), and transforming growth factor β1 (TGF- β1), engineering an anisotropic biomimetic fibrocartilage microenvironment. Assessment of the model tissue construct displayed multiphasic anisotropy of the incorporated biochemical factors after patterning. Quantitative real time polymerase chain reaction (qRT-PCR) results suggested genomic expression patterns leading to simultaneous differentiation of MSC populations into osteogenic and chondrogenic phenotype within the multiphasic construct, evidenced by upregulation of osteogenesis and condrogenesis related genes during in vitro culture. Comprehensive phenotypic network and pathway analysis results, which were based on genomic expression data, indicated activation of differentiation related mechanisms, via signaling pathways, including TGF, BMP, and vascular endothelial growth factor.

Engineering Anisotropic Biomimetic Fibrocartilage Microenvironment by Bioprinting Mesenchymal Stem Cells in Nanoliter Gel Droplets

Science.gov (United States)

2015-01-01

Over the past decade, bioprinting has emerged as a promising patterning strategy to organize cells and extracellular components both in two and three dimensions (2D and 3D) to engineer functional tissue mimicking constructs. So far, tissue printing has neither been used for 3D patterning of mesenchymal stem cells (MSCs) in multiphase growth factor embedded 3D hydrogels nor been investigated phenotypically in terms of simultaneous differentiation into different cell types within the same micropatterned 3D tissue constructs. Accordingly, we demonstrated a biochemical gradient by bioprinting nanoliter droplets encapsulating human MSCs, bone morphogenetic protein 2 (BMP-2), and transforming growth factor β1 (TGF- β1), engineering an anisotropic biomimetic fibrocartilage microenvironment. Assessment of the model tissue construct displayed multiphasic anisotropy of the incorporated biochemical factors after patterning. Quantitative real time polymerase chain reaction (qRT-PCR) results suggested genomic expression patterns leading to simultaneous differentiation of MSC populations into osteogenic and chondrogenic phenotype within the multiphasic construct, evidenced by upregulation of osteogenesis and condrogenesis related genes during in vitro culture. Comprehensive phenotypic network and pathway analysis results, which were based on genomic expression data, indicated activation of differentiation related mechanisms, via signaling pathways, including TGF, BMP, and vascular endothelial growth factor. PMID:24495169

Dynamic Reciprocity in the Wound Microenvironment

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Schultz, Gregory S.; Davidson, Jeffrey M.; Kirsner, Robert S.; Bornstein, Paul; Herman, Ira M.

2011-01-01

Here, we define dynamic reciprocity (DR) as an ongoing, bidirectional interaction amongst cells and their surrounding microenvironment. In the review, we posit that DR is especially meaningful during wound healing as the DR-driven biochemical, biophysical and cellular responses to injury play pivotal roles in regulating tissue regenerative responses. Such cell-extracellular matrix interactions not only guide and regulate cellular morphology, but cellular differentiation, migration, proliferation, and survival during tissue development, including e.g. embryogenesis, angiogenesis, as well as during pathologic processes including cancer diabetes, hypertension and chronic wound healing. Herein, we examine DR within the wound microenvironment while considering specific examples across acute and chronic wound healing. This review also considers how a number of hypotheses that attempt to explain chronic wound pathophysiology, which may be understood within the DR framework. The implications of applying the principles of dynamic reciprocity to optimize wound care practice and future development of innovative wound healing therapeutics are also briefly considered. PMID:21362080

Microfluidic systems for stem cell-based neural tissue engineering.

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Karimi, Mahdi; Bahrami, Sajad; Mirshekari, Hamed; Basri, Seyed Masoud Moosavi; Nik, Amirala Bakhshian; Aref, Amir R; Akbari, Mohsen; Hamblin, Michael R

2016-07-05

Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a "brain-on-a-chip". In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

KEY FEATURES OF THE INTRAGRAFT MICROENVIRONMENT THAT DETERMINE LONG-TERM SURVIVAL FOLLOWING TRANSPLANTATION

Directory of Open Access Journals (Sweden)

Sarah eBruneau

2012-04-01

Full Text Available In this review, we discuss how changes in the intragraft microenvironment serve to promote or sustain the development of chronic allograft rejection. We propose two key elements within the microenvironment that contribute to the rejection process. The first is endothelial cell proliferation and angiogenesis that serve to create abnormal microvascular blood flow patterns as well as local tissue hypoxia, and precedes endothelial-to-mesenchymal transition (EndMT. The second is the overexpression of local cytokines and growth factors that serve to sustain inflammation and, in turn, function to promote a leukocyte-induced angiogenesis reaction. Central to both events is overexpression of vascular endothelial growth factor (VEGF, which is both pro-inflammatory and pro-angiogenic, and thus drives progression of the chronic rejection microenvironment. In our discussion, we focus on how inflammation results in angiogenesis and how leukocyte-induced angiogenesis is pathological. We also discuss how VEGF is a master control factor that fosters the development of the chronic rejection microenvironment. Overall, this review provides insight into the intragraft microenvironment as an important paradigm for future direction in the field.

Key Features of the Intragraft Microenvironment that Determine Long-Term Survival Following Transplantation

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Bruneau, Sarah; Woda, Craig Bryan; Daly, Kevin Patrick; Boneschansker, Leonard; Jain, Namrata Gargee; Kochupurakkal, Nora; Contreras, Alan Gabriel; Seto, Tatsuichiro; Briscoe, David Michael

2012-01-01

In this review, we discuss how changes in the intragraft microenvironment serve to promote or sustain the development of chronic allograft rejection. We propose two key elements within the microenvironment that contribute to the rejection process. The first is endothelial cell proliferation and angiogenesis that serve to create abnormal microvascular blood flow patterns as well as local tissue hypoxia, and precedes endothelial-to-mesenchymal transition. The second is the overexpression of local cytokines and growth factors that serve to sustain inflammation and, in turn, function to promote a leukocyte-induced angiogenesis reaction. Central to both events is overexpression of vascular endothelial growth factor (VEGF), which is both pro-inflammatory and pro-angiogenic, and thus drives progression of the chronic rejection microenvironment. In our discussion, we focus on how inflammation results in angiogenesis and how leukocyte-induced angiogenesis is pathological. We also discuss how VEGF is a master control factor that fosters the development of the chronic rejection microenvironment. Overall, this review provides insight into the intragraft microenvironment as an important paradigm for future direction in the field. PMID:22566935

Interaction of tumor cells with the microenvironment

Directory of Open Access Journals (Sweden)

Lehnert Hendrik

2011-09-01

Full Text Available Abstract Recent advances in tumor biology have revealed that a detailed analysis of the complex interactions of tumor cells with their adjacent microenvironment (tumor stroma is mandatory in order to understand the various mechanisms involved in tumor growth and the development of metastasis. The mutual interactions between tumor cells and cellular and non-cellular components (extracellular matrix = ECM of the tumor microenvironment will eventually lead to a loss of tissue homeostasis and promote tumor development and progression. Thus, interactions of genetically altered tumor cells and the ECM on the one hand and reactive non-neoplastic cells on the other hand essentially control most aspects of tumorigenesis such as epithelial-mesenchymal-transition (EMT, migration, invasion (i.e. migration through connective tissue, metastasis formation, neovascularisation, apoptosis and chemotherapeutic drug resistance. In this mini-review we will focus on these issues that were recently raised by two review articles in CCS.

Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

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Jaehong Kim

2016-01-01

Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

Naturally Engineered Maturation of Cardiomyocytes

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Gaetano J. Scuderi

2017-05-01

Full Text Available Ischemic heart disease remains one of the most prominent causes of mortalities worldwide with heart transplantation being the gold-standard treatment option. However, due to the major limitations associated with heart transplants, such as an inadequate supply and heart rejection, there remains a significant clinical need for a viable cardiac regenerative therapy to restore native myocardial function. Over the course of the previous several decades, researchers have made prominent advances in the field of cardiac regeneration with the creation of in vitro human pluripotent stem cell-derived cardiomyocyte tissue engineered constructs. However, these engineered constructs exhibit a functionally immature, disorganized, fetal-like phenotype that is not equivalent physiologically to native adult cardiac tissue. Due to this major limitation, many recent studies have investigated approaches to improve pluripotent stem cell-derived cardiomyocyte maturation to close this large functionality gap between engineered and native cardiac tissue. This review integrates the natural developmental mechanisms of cardiomyocyte structural and functional maturation. The variety of ways researchers have attempted to improve cardiomyocyte maturation in vitro by mimicking natural development, known as natural engineering, is readily discussed. The main focus of this review involves the synergistic role of electrical and mechanical stimulation, extracellular matrix interactions, and non-cardiomyocyte interactions in facilitating cardiomyocyte maturation. Overall, even with these current natural engineering approaches, pluripotent stem cell-derived cardiomyocytes within three-dimensional engineered heart tissue still remain mostly within the early to late fetal stages of cardiomyocyte maturity. Therefore, although the end goal is to achieve adult phenotypic maturity, more emphasis must be placed on elucidating how the in vivo fetal microenvironment drives cardiomyocyte

Roles of stromal microenvironment in colon cancer progression.

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Taketo, Makoto Mark

2012-05-01

Although our understanding of epithelial cancer cells has advanced significantly, our understanding of the cancer microenvironment is still fragmentary. In contrast to our intuitive impression that our body always suppresses cancer growth, recent pieces of evidence show that cancer often exploits our body reactions to expand, invade local tissues and metastasize to distant organs. Accordingly, investigations of such body reactions in the tumour microenvironment should help us to design novel therapeutic strategies that can be combined with the traditional therapeutics targeted at the cancer cells themselves. In this article, I am going to review our recent efforts in search of novel therapeutic strategies against colon cancer using mouse models.

Immunological dysregulation in multiple myeloma microenvironment.

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Romano, Alessandra; Conticello, Concetta; Cavalli, Maide; Vetro, Calogero; La Fauci, Alessia; Parrinello, Nunziatina Laura; Di Raimondo, Francesco

2014-01-01

Multiple Myeloma (MM) is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and PC themselves. All these components are able to protect PC from cytotoxic effect of chemo- and radiotherapy. This review is focused on the role of immunome to sustain MM progression, the emerging role of myeloid derived suppressor cells, and their potential clinical implications as novel therapeutic target.

Immunological Dysregulation in Multiple Myeloma Microenvironment

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Alessandra Romano

2014-01-01

Full Text Available Multiple Myeloma (MM is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC in bone marrow (BM. Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and PC themselves. All these components are able to protect PC from cytotoxic effect of chemo- and radiotherapy. This review is focused on the role of immunome to sustain MM progression, the emerging role of myeloid derived suppressor cells, and their potential clinical implications as novel therapeutic target.

Lysyl Oxidase and the Tumor Microenvironment

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Tong-Hong Wang

2016-12-01

Full Text Available The lysyl oxidase (LOX family of oxidases contains a group of extracellular copper-dependent enzymes that catalyze the cross-linking of collagen and elastin by oxidation, thus maintaining the rigidity and structural stability of the extracellular matrix (ECM. Aberrant expression or activation of LOX alters the cellular microenvironment, leading to many diseases, including atherosclerosis, tissue fibrosis, and cancer. Recently, a number of studies have shown that LOX is overexpressed in most cancers and that it is involved in the regulation of tumor progression and metastasis. In contrast, a few reports have also indicated the tumor-suppressing role of LOX. In this short review, we discuss recent research on the correlations between LOX and cancer. Further, the role of LOX in tumor microenvironment remodeling, tumorigenesis, and metastasis and the underlying mechanisms have also been elucidated.

The PCa Tumor Microenvironment.

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Sottnik, Joseph L; Zhang, Jian; Macoska, Jill A; Keller, Evan T

2011-12-01

The tumor microenvironment (TME) is a very complex niche that consists of multiple cell types, supportive matrix and soluble factors. Cells in the TME consist of both host cells that are present at tumor site at the onset of tumor growth and cells that are recruited in either response to tumor- or host-derived factors. PCa (PCa) thrives on crosstalk between tumor cells and the TME. Crosstalk results in an orchestrated evolution of both the tumor and microenvironment as the tumor progresses. The TME reacts to PCa-produced soluble factors as well as direct interaction with PCa cells. In return, the TME produces soluble factors, structural support and direct contact interactions that influence the establishment and progression of PCa. In this review, we focus on the host side of the equation to provide a foundation for understanding how different aspects of the TME contribute to PCa progression. We discuss immune effector cells, specialized niches, such as the vascular and bone marrow, and several key protein factors that mediate host effects on PCa. This discussion highlights the concept that the TME offers a potentially very fertile target for PCa therapy.

Impact of Microenvironment and Stem-Like Plasticity in Cholangiocarcinoma

DEFF Research Database (Denmark)

Raggi, Chiara; Invernizzi, Pietro; Andersen, Jesper Bøje

2014-01-01

or tumor microenvironment (TME) likely promotes initiation and progression of this malignancy contributing to its heterogeneity. This review will emphasize the dynamic interplay between stem-like intrinsic and TME-extrinsic pathways, which may represent novel options for multi-targeted therapies in CCA....

Mechanical Engineering Department technical review

Energy Technology Data Exchange (ETDEWEB)

Carr, R.B.; Abrahamson, L.; Denney, R.M.; Dubois, B.E (eds.)

1982-01-01

Technical achievements and publication abstracts related to research in the following Divisions of Lawrence Livermore Laboratory are reported in this biannual review: Nuclear Fuel Engineering; Nuclear Explosives Engineering; Weapons Engineering; Energy Systems Engineering; Engineering Sciences; Magnetic Fusion Engineering; and Material Fabrication. (LCL)

Aerobic glycolysis and high level of lactate in cancer metabolism and microenvironment

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Bo Jiang

2017-03-01

Full Text Available Metabolic abnormalities is a hallmark of cancer. About 100 years ago, Nobel laureate Otto Heinrich Warburg first described high rate of glycolysis in cancer cells. Recently more and more novel opinions about cancer metabolism supplement to this hypothesis, consist of glucose uptake, lactic acid generation and secretion, acidification of the microenvironment and cancer immune evasion. Here we briefly review metabolic pathways generating lactate, and discuss the function of higher lactic acid in cancer microenvironments.

Immune Microenvironment in Colorectal Cancer: A New Hallmark to Change Old Paradigms

OpenAIRE

de la Cruz-Merino, Luis; Henao Carrasco, Fernando; Vicente Baz, David; Nogales Fernández, Esteban; Reina Zoilo, Juan José; Codes Manuel de Villena, Manuel; Pulido, Enrique Grande

2011-01-01

Impact of immune microenvironment in prognosis of solid tumors has been extensively studied in the last few years. Specifically in colorectal carcinoma, increased knowledge of the immune events around these tumors and their relation with clinical outcomes have led to consider immune microenvironment as one of the most important prognostic factors in this disease. In this review we will summarize and update the current knowledge with respect to this intriguing and complex new hallmark of cance...

Royal Society Scientific Meeting: Extracellular vesicles in the tumour microenvironment.

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Pink, Ryan Charles; Elmusrati, Areeg A; Lambert, Daniel; Carter, David Raul Francisco

2018-01-05

Cancer cells do not grow as an isolated homogeneous mass; tumours are, in fact, complex and heterogeneous collections of cancer and surrounding stromal cells, collectively termed the tumour microenvironment. The interaction between cancer cells and stromal cells in the tumour microenvironment has emerged as a key concept in the regulation of cancer progression. Understanding the intercellular dialogue in the tumour microenvironment is therefore an important goal. One aspect of this dialogue that has not been appreciated until recently is the role of extracellular vesicles (EVs). EVs are small vesicles released by cells under both normal and pathological conditions; they can transfer biological molecules between cells leading to changes in phenotype. EVs have emerged as important regulators of biological processes and can be dysregulated in diseases such as cancer; rapidly growing interest in their biology and therapeutic potential led to the Royal Society hosting a Scientific Meeting to explore the roles of EVs in the tumour microenvironment. This cross-disciplinary meeting explored examples of how aberrant crosstalk between tumour and stromal cells can promote cancer progression, and how such signalling can be targeted for diagnostic, prognostic and therapeutic benefit. In this review, and the special edition of Philosophical Transactions of the Royal Society B that follows, we will provide an overview of the content and outcomes of this exciting meeting.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'. © 2017 The Author(s).

Targeting the tumor microenvironment

Energy Technology Data Exchange (ETDEWEB)

Kenny, P.A.; Lee, G.Y.; Bissell, M.J.

2006-11-07

Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and review the approaches being taken to disrupt these interactions.

Influence of the Tumor Microenvironment on Cancer Cells Metabolic Reprogramming

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Victoire Gouirand

2018-04-01

Full Text Available As with castles, tumor cells are fortified by surrounding non-malignant cells, such as cancer-associated fibroblasts, immune cells, but also nerve fibers and extracellular matrix. In most cancers, this fortification creates a considerable solid pressure which limits oxygen and nutrient delivery to the tumor cells and causes a hypoxic and nutritional stress. Consequently, tumor cells have to adapt their metabolism to survive and proliferate in this harsh microenvironment. To satisfy their need in energy and biomass, tumor cells develop new capacities to benefit from metabolites of the microenvironment, either by their uptake through the macropinocytosis process or through metabolite transporters, or by a cross-talk with stromal cells and capture of extracellular vesicles that are released by the neighboring cells. However, the microenvironments of primary tumor and metastatic niches differ tremendously in their cellular/acellular components and available nutrients. Therefore, cancer cells must develop a metabolic flexibility conferring on them the ability to satisfy their biomass and energetic demands at both primary and metastasis sites. In this review, we propose a brief overview of how proliferating cancer cells take advantage of their surrounding microenvironment to satisfy their high metabolic demand at both primary and metastasis sites.

Assembly of hydrogel units for 3D microenvironment in a poly(dimethylsiloxane) channel

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Cho, Chang Hyun; Kwon, Seyong; Park, Je-Kyun

2017-12-01

Construction of three-dimensional (3D) microenvironment become an important issue in recent biological studies due to their biological relevance compared to conventional two-dimensional (2D) microenvironment. Various fabrication techniques have been employed to construct a 3D microenvironment, however, it is difficult to fully satisfy the biological and mechanical properties required for the 3D cell culture system, such as heterogeneous tissue structures generated from the functional differences or diseases. We propose here an assembly method for facile construction of 3D microenvironment in a poly(dimethylsiloxane) (PDMS) channel using hydrogel units. The high-aspect-ratio of hydrogel units was achieved by fabricating these units using a 2D mold. With this approach, 3D heterogeneous hydrogel units were produced and assembled in a PDMS channel by structural hookup. In vivo-like 3D heterogeneous microenvironment in a precisely controllable fluidic system was also demonstrated using a controlled assembly of different types of hydrogel units, which was difficult to obtain from previous methods. By regulating the flow condition, the mechanical stability of the assembled hydrogel units was verified by the flow-induced deformation of hydrogel units. In addition, in vivo-like cell culture environment was demonstrated using an assembly of cell-coated hydrogel units in the fluidic channel. Based on these features, our method expects to provide a beneficial tool for the 3D cell culture module and biomimetic engineering.

Software Engineering Reviews and Audits

CERN Document Server

Summers, Boyd L

2011-01-01

Accurate software engineering reviews and audits have become essential to the success of software companies and military and aerospace programs. These reviews and audits define the framework and specific requirements for verifying software development efforts. Authored by an industry professional with three decades of experience, Software Engineering Reviews and Audits offers authoritative guidance for conducting and performing software first article inspections, and functional and physical configuration software audits. It prepares readers to answer common questions for conducting and perform

The external microenvironment of healing skin wounds

DEFF Research Database (Denmark)

Kruse, Carla R; Nuutila, Kristo; Lee, Cameron Cy

2015-01-01

The skin wound microenvironment can be divided into two main components that influence healing: the external wound microenvironment, which is outside the wound surface; and the internal wound microenvironment, underneath the surface, to which the cells within the wound are exposed. Treatment...

Reprograming the Metastatic Microenvironment to Combat Disease Recurrence

Science.gov (United States)

2017-10-01

0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing...truly eliminate “residual disease” and prevent metastatic recurrence. We believe we have found a way to accomplish this by inhibiting colony- stimulating ...the bone microenvironment lead to pathological bone loss, which can stimulate tumor cell outgrowth. In addition to contributing to morbidity, this

Intraportal islet transplantation: the impact of the liver microenvironment.

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Delaune, Vaihere; Berney, Thierry; Lacotte, Stéphanie; Toso, Christian

2017-03-01

The portal vein remains the preferred site for pancreatic islet transplantation due to its easy access and low morbidity. However, despite great progress in isolation and transplantation protocols over the past few years, it is still associated with the early loss of some 50-70% of transplanted islets. The complex liver microenvironment itself presumably plays an important role in this loss. The present review focuses on the specifics of the liver microenvironment, notably the localized hepatic ischemia/reperfusion injury following transplantation, the low oxygenation of the portal vein, the instant blood-mediated inflammatory reaction, the endogenous liver immune system, and the gut-liver axis, and how they can each have an impact on the transplanted islets. It identifies the potential, or already applied, clinical interventions for improving intraportal islet survival, and pinpoints those promising areas still lacking preclinical research. Future interventions on clinical intraportal islet transplantation need to take into account the global context of the liver microenvironment, with multi-point interventions being most likely to improve early islet survival and engraftment. © 2017 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.

Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

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Bo Zhang

2017-12-01

Full Text Available Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents.

Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

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Zhang, Bo; Hu, Yu; Pang, Zhiqing

2017-01-01

Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR) effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents. PMID:29311946

Role of tumor microenvironment in triple-negative breast cancer and its prognostic significance

Institute of Scientific and Technical Information of China (English)

Tianjian Yu; Genhong Di

2017-01-01

Breast cancer has been shown to live in the tumor microenvironment,which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells.Diverse components of the breast cancer microenvironment,such as suppressive immune cells,re-programmed fibroblast cells,altered extracellular matrix (ECM) and certain soluble factors,synergistically impede an effective anti-tumor response and promote breast cancer progression and metastasis.Among these components,stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways,whereas the ECM features biochemical and biomechanical changes.However,triple-negative breast cancer (TNBC),the most aggressive subtype of this disease that lacks effective therapies available for other subtypes,is considered to feature a unique microenvironment distinct from that of other subtypes,especially compared to Luminal A subtype.Because these changes are now considered to significantly impact breast cancer development and progression,these unique alterations may serve as promising prognostic factors of clinical outcome or potential therapeutic targets for the treatment of TNBC.In this review,we focus on the composition of the TNBC microenvironment,concomitant distinct biological alteration,specific interplay between various cell types and TNBC cells,and the prognostic implications of these findings.

Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

International Nuclear Information System (INIS)

Chanmee, Theerawut; Ontong, Pawared; Konno, Kenjiro; Itano, Naoki

2014-01-01

During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy

Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

Energy Technology Data Exchange (ETDEWEB)

Chanmee, Theerawut [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Ontong, Pawared [Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Konno, Kenjiro [Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Itano, Naoki, E-mail: itanon@cc.kyoto-su.ac.jp [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan)

2014-08-13

During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy.

Acidic tumor microenvironment and pH-sensing G protein-coupled receptors.

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Justus, Calvin R; Dong, Lixue; Yang, Li V

2013-12-05

The tumor microenvironment is acidic due to glycolytic cancer cell metabolism, hypoxia, and deficient blood perfusion. It is proposed that acidosis in the tumor microenvironment is an important stress factor and selection force for cancer cell somatic evolution. Acidic pH has pleiotropic effects on the proliferation, migration, invasion, metastasis, and therapeutic response of cancer cells and the function of immune cells, vascular cells, and other stromal cells. However, the molecular mechanisms by which cancer cells and stromal cells sense and respond to acidic pH in the tumor microenvironment are poorly understood. In this article the role of a family of pH-sensing G protein-coupled receptors (GPCRs) in tumor biology is reviewed. Recent studies show that the pH-sensing GPCRs, including GPR4, GPR65 (TDAG8), GPR68 (OGR1), and GPR132 (G2A), regulate cancer cell metastasis and proliferation, immune cell function, inflammation, and blood vessel formation. Activation of the proton-sensing GPCRs by acidosis transduces multiple downstream G protein signaling pathways. Since GPCRs are major drug targets, small molecule modulators of the pH-sensing GPCRs are being actively developed and evaluated. Research on the pH-sensing GPCRs will continue to provide important insights into the molecular interaction between tumor and its acidic microenvironment and may identify new targets for cancer therapy and chemoprevention.

Molecular imaging of the tumor microenvironment for precision medicine and theranostics.

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Penet, Marie-France; Krishnamachary, Balaji; Chen, Zhihang; Jin, Jiefu; Bhujwalla, Zaver M

2014-01-01

Morbidity and mortality from cancer and their associated conditions and treatments continue to extract a heavy social and economic global burden despite the transformative advances in science and technology in the twenty-first century. In fact, cancer incidence and mortality are expected to reach pandemic proportions by 2025, and costs of managing cancer will escalate to trillions of dollars. The inability to establish effective cancer treatments arises from the complexity of conditions that exist within tumors, the plasticity and adaptability of cancer cells coupled with their ability to escape immune surveillance, and the co-opted stromal cells and microenvironment that assist cancer cells in survival. Stromal cells, although destroyed together with cancer cells, have an ever-replenishing source that can assist in resurrecting tumors from any residual cancer cells that may survive treatment. The tumor microenvironment landscape is a continually changing landscape, with spatial and temporal heterogeneities that impact and influence cancer treatment outcome. Importantly, the changing landscape of the tumor microenvironment can be exploited for precision medicine and theranostics. Molecular and functional imaging can play important roles in shaping and selecting treatments to match this landscape. Our purpose in this review is to examine the roles of molecular and functional imaging, within the context of the tumor microenvironment, and the feasibility of their applications for precision medicine and theranostics in humans. © 2014 Elsevier Inc. All rights reserved.

Radiofrequency electromagnetic field exposure in everyday microenvironments in Europe: A systematic literature review.

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Sagar, Sanjay; Dongus, Stefan; Schoeni, Anna; Roser, Katharina; Eeftens, Marloes; Struchen, Benjamin; Foerster, Milena; Meier, Noëmi; Adem, Seid; Röösli, Martin

2018-03-01

The impact of the introduction and advancement in communication technology in recent years on exposure level of the population is largely unknown. The main aim of this study is to systematically review literature on the distribution of radiofrequency electromagnetic field (RF-EMF) exposure in the everyday environment in Europe and summarize key characteristics of various types of RF-EMF studies conducted in the European countries. We systematically searched the ISI Web of Science for relevant literature published between 1 January 2000 and 30 April 2015, which assessed RF-EMF exposure levels by any of the methods: spot measurements, personal measurement with trained researchers and personal measurement with volunteers. Twenty-one published studies met our eligibility criteria of which 10 were spot measurements studies, 5 were personal measurement studies with trained researchers (microenvironmental), 5 were personal measurement studies with volunteers and 1 was a mixed methods study combining data collected by volunteers and trained researchers. RF-EMF data included in the studies were collected between 2005 and 2013. The mean total RF-EMF exposure for spot measurements in European "Homes" and "Outdoor" microenvironments was 0.29 and 0.54 V/m, respectively. In the personal measurements studies with trained researchers, the mean total RF-EMF exposure was 0.24 V/m in "Home" and 0.76 V/m in "Outdoor". In the personal measurement studies with volunteers, the population weighted mean total RF-EMF exposure was 0.16 V/m in "Homes" and 0.20 V/m in "Outdoor". Among all European microenvironments in "Transportation", the highest mean total RF-EMF 1.96 V/m was found in trains of Belgium during 2007 where more than 95% of exposure was contributed by uplink. Typical RF-EMF exposure levels are substantially below regulatory limits. We found considerable differences between studies according to the type of measurements procedures, which precludes cross

Engineering Musculoskeletal Tissue Interfaces

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Ece Bayrak

2018-04-01

Full Text Available Tissue engineering aims to bring together biomaterials, cells, and signaling molecules within properly designed microenvironments in order to create viable treatment options for the lost or malfunctioning tissues. Design and production of scaffolds and cell-laden grafts that mimic the complex structural and functional features of tissues are among the most important elements of tissue engineering strategy. Although all tissues have their own complex structure, an even more complex case in terms of engineering a proper carrier material is encountered at the tissue interfaces, where two distinct tissues come together. The interfaces in the body can be examined in four categories; cartilage-bone and ligament-bone interfaces at the knee and the spine, tendon-bone interfaces at the shoulder and the feet, and muscle-tendon interface at the skeletal system. These interfaces are seen mainly at the soft-to-hard tissue transitions and they are especially susceptible to injury and tear due to the biomechanical inconsistency between these tissues where high strain fields are present. Therefore, engineering the musculoskeletal tissue interfaces remain a challenge. This review focuses on recent advancements in strategies for musculoskeletal interface engineering using different biomaterial-based platforms and surface modification techniques.

Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment

Science.gov (United States)

Cruz-Monserrate, Zobeida; Roland, Christina L.; Deng, Defeng; Arumugam, Thiruvengadam; Moshnikova, Anna; Andreev, Oleg A.; Reshetnyak, Yana K.; Logsdon, Craig D.

2014-03-01

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for ~40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that is highly operator dependent. Here we took advantage of a general characteristic of solid tumors, the acidic microenvironment that is generated as a by-product of metabolism, to develop a novel approach of using pH (Low) Insertion Peptides (pHLIPs) for imaging of PDAC. We show that fluorescently labeled pHLIPs can localize and specifically detect PDAC in human xenografts as well as PDAC and PanIN lesions in genetically engineered mouse models. This novel approach may improve detection, differential diagnosis and staging of PDAC.

Remodeling the blood–brain barrier microenvironment by natural products for brain tumor therapy

Institute of Scientific and Technical Information of China (English)

Xiao Zhao; Rujing Chen; Mei Liu; Jianfang Feng; Jun Chen; Kaili Hu

2017-01-01

Brain tumor incidence shows an upward trend in recent years; brain tumors account for 5% of adult tumors, while in children, this figure has increased to 70%. Moreover, 20%–30% of malignant tumors will eventually metastasize into the brain. Both benign and malignant tumors can cause an increase in intracranial pressure and brain tissue compression, leading to central nervous system(CNS) damage which endangers the patients’ lives. Despite the many approaches to treating brain tumors and the progress that has been made, only modest gains in survival time of brain tumor patients have been achieved. At present, chemotherapy is the treatment of choice for many cancers, but the special structure of the blood–brain barrier(BBB) limits most chemotherapeutic agents from passing through the BBB and penetrating into tumors in the brain. The BBB microenvironment contains numerous cell types, including endothelial cells, astrocytes, peripheral cells and microglia, and extracellular matrix(ECM). Many chemical components of natural products are reported to regulate the BBB microenvironment near brain tumors and assist in their treatment. This review focuses on the composition and function of the BBB microenvironment under both physiological and pathological conditions, and the current research progress in regulating the BBB microenvironment by natural products to promote the treatment of brain tumors.

Nanomaterials for Engineering Stem Cell Responses.

Science.gov (United States)

Kerativitayanan, Punyavee; Carrow, James K; Gaharwar, Akhilesh K

2015-08-05

Recent progress in nanotechnology has stimulated the development of multifunctional biomaterials for tissue engineering applications. Synergistic interactions between nanomaterials and stem cell engineering offer numerous possibilities to address some of the daunting challenges in regenerative medicine, such as controlling trigger differentiation, immune reactions, limited supply of stem cells, and engineering complex tissue structures. Specifically, the interactions between stem cells and their microenvironment play key roles in controlling stem cell fate, which underlines therapeutic success. However, the interactions between nanomaterials and stem cells are not well understood, and the effects of the nanomaterials shape, surface morphology, and chemical functionality on cellular processes need critical evaluation. In this Review, focus is put on recent development in nanomaterial-stem cell interactions, with specific emphasis on their application in regenerative medicine. Further, the emerging technologies based on nanomaterials developed over the past decade for stem cell engineering are reviewed, as well as the potential applications of these nanomaterials in tissue regeneration, stem cell isolation, and drug/gene delivery. It is anticipated that the enhanced understanding of nanomaterial-stem cell interactions will facilitate improved biomaterial design for a range of biomedical and biotechnological applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tumor Microenvironment and Immune Effects of Antineoplastic Therapy in Lymphoproliferative Syndromes

Science.gov (United States)

Álvaro, Tomás; de la Cruz-Merino, Luis; Henao-Carrasco, Fernando; Villar Rodríguez, José Luis; Vicente Baz, David; Codes Manuel de Villena, Manuel; Provencio, Mariano

2010-01-01

Lymphomas represent a wide group of heterogenic diseases with different biological and clinical behavior. The underlying microenvironment-specific composition seems to play an essential role in this scenario, harboring the ability to develop successful immune responses or, on the contrary, leading to immune evasion and even promotion of tumor growth. Depending on surrounding lymphoid infiltrates, lymphomas may have different prognosis. Moreover, recent evidences have emerged that confer a significant impact of main lymphoma's treatment over microenvironment, with clinical consequences. In this review, we summarize these concepts from a pathological and clinical perspective. Also, the state of the art of lymphoma's anti-idiotype vaccine development is revised, highlighting the situations where this strategy has proven to be successful and eventual clues to obtain better results in the future. PMID:20814546

Mechanical Engineering Department Technical Review

International Nuclear Information System (INIS)

Carr, R.B.; Denney, R.M.

1981-01-01

The Mechanical Engineering Department Technical Review is published to inform readers of various technical activities within the Department, promote exchange of ideas, and give credit to personnel who are achieving the results. The report is presented in two parts: technical achievements and publication abstracts. The first is divided into seven sections, each of which reports on an engineering division and its specific activities related to nuclear tests, nuclear explosives, weapons, energy systems, engineering sciences, magnetic fusion, and materials fabrication

Immune microenvironment in colorectal cancer: a new hallmark to change old paradigms.

Science.gov (United States)

de la Cruz-Merino, Luis; Henao Carrasco, Fernando; Vicente Baz, David; Nogales Fernández, Esteban; Reina Zoilo, Juan José; Codes Manuel de Villena, Manuel; Pulido, Enrique Grande

2011-01-01

Impact of immune microenvironment in prognosis of solid tumors has been extensively studied in the last few years. Specifically in colorectal carcinoma, increased knowledge of the immune events around these tumors and their relation with clinical outcomes have led to consider immune microenvironment as one of the most important prognostic factors in this disease. In this review we will summarize and update the current knowledge with respect to this intriguing and complex new hallmark of cancer, paying special attention to infiltration by T-infiltrating lymphocytes and their subtypes in colorectal cancer, as well as its eventual clinical translation in terms of long-term prognosis. Finally, we suggest some possible investigational approaches based on combinatorial strategies to trigger and boost immune reaction against tumor cells.

Pericyte-targeting drug delivery and tissue engineering

Directory of Open Access Journals (Sweden)

Kang E

2016-05-01

Full Text Available Eunah Kang,1 Jong Wook Shin2 1School of Chemical Engineering and Material Science, 2Division of Allergic and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, Chung-Ang University, Dongjak-Gu, Seoul, South Korea Abstract: Pericytes are contractile mural cells that wrap around the endothelial cells of capillaries and venules. Depending on the triggers by cellular signals, pericytes have specific functionality in tumor microenvironments, properties of potent stem cells, and plasticity in cellular pathology. These features of pericytes can be activated for the promotion or reduction of angiogenesis. Frontier studies have exploited pericyte-targeting drug delivery, using pericyte-specific peptides, small molecules, and DNA in tumor therapy. Moreover, the communication between pericytes and endothelial cells has been applied to the induction of vessel neoformation in tissue engineering. Pericytes may prove to be a novel target for tumor therapy and tissue engineering. The present paper specifically reviews pericyte-specific drug delivery and tissue engineering, allowing insight into the emerging research targeting pericytes. Keywords: pericytes, pericyte-targeting drug delivery, tissue engineering, platelet-derived growth factor, angiogenesis, vascular remodeling

Optical microassembly platform for constructing reconfigurable microenvironment for biomedical studies

DEFF Research Database (Denmark)

Rodrigo, Peter John; Kelemen, Lóránd; Palima, Darwin

2009-01-01

Cellular development is highly influenced by the surrounding microenvironment. We propose user-reconfigurable microenvironments and bio-compatible scaffolds as an approach for understanding cellular development processes. We demonstrate a model platform for constructing versatile microenvironment...

Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment.

Science.gov (United States)

Ito, Koichi; Stannard, Kimberley; Gabutero, Elwyn; Clark, Amanda M; Neo, Shi-Yong; Onturk, Selda; Blanchard, Helen; Ralph, Stephen J

2012-12-01

The microenvironment of a tumor is a highly complex milieu, primarily characterized by immunosuppression, abnormal angiogenesis, and hypoxic regions. These features promote tumor progression and metastasis, resulting in poor prognosis and greater resistance to existing cancer therapies. Galectin-1 is a β-galactoside binding protein that is abundantly secreted by almost all types of malignant tumor cells. The expression of galectin-1 is regulated by hypoxia-inducible factor-1 (HIF-1) and it plays vital pro-tumorigenic roles within the tumor microenvironment. In particular, galectin-1 suppresses T cell-mediated cytotoxic immune responses and promotes tumor angiogenesis. However, since galectin-1 displays many different activities by binding to a number of diverse N- or O-glycan modified target proteins, it has been difficult to fully understand how galectin-1 supports tumor growth and metastasis. This review explores the importance of galectin-1 and glycan expression patterns in the tumor microenvironment and the potential effects of inhibiting galectin-1 as a therapeutic target for cancer treatment.

Enduring epigenetic landmarks define the cancer microenvironment

Science.gov (United States)

Pidsley, Ruth; Lawrence, Mitchell G.; Zotenko, Elena; Niranjan, Birunthi; Statham, Aaron; Song, Jenny; Chabanon, Roman M.; Qu, Wenjia; Wang, Hong; Richards, Michelle; Nair, Shalima S.; Armstrong, Nicola J.; Nim, Hieu T.; Papargiris, Melissa; Balanathan, Preetika; French, Hugh; Peters, Timothy; Norden, Sam; Ryan, Andrew; Pedersen, John; Kench, James; Daly, Roger J.; Horvath, Lisa G.; Stricker, Phillip; Frydenberg, Mark; Taylor, Renea A.; Stirzaker, Clare; Risbridger, Gail P.; Clark, Susan J.

2018-01-01

The growth and progression of solid tumors involves dynamic cross-talk between cancer epithelium and the surrounding microenvironment. To date, molecular profiling has largely been restricted to the epithelial component of tumors; therefore, features underpinning the persistent protumorigenic phenotype of the tumor microenvironment are unknown. Using whole-genome bisulfite sequencing, we show for the first time that cancer-associated fibroblasts (CAFs) from localized prostate cancer display remarkably distinct and enduring genome-wide changes in DNA methylation, significantly at enhancers and promoters, compared to nonmalignant prostate fibroblasts (NPFs). Differentially methylated regions associated with changes in gene expression have cancer-related functions and accurately distinguish CAFs from NPFs. Remarkably, a subset of changes is shared with prostate cancer epithelial cells, revealing the new concept of tumor-specific epigenome modifications in the tumor and its microenvironment. The distinct methylome of CAFs provides a novel epigenetic hallmark of the cancer microenvironment and promises new biomarkers to improve interpretation of diagnostic samples. PMID:29650553

Nanoscale tissue engineering: spatial control over cell-materials interactions

International Nuclear Information System (INIS)

Wheeldon, Ian; Farhadi, Arash; Bick, Alexander G; Khademhosseini, Ali; Jabbari, Esmaiel

2011-01-01

Cells interact with the surrounding environment by making tens to hundreds of thousands of nanoscale interactions with extracellular signals and features. The goal of nanoscale tissue engineering is to harness these interactions through nanoscale biomaterials engineering in order to study and direct cellular behavior. Here, we review two- and three-dimensional (2- and 3D) nanoscale tissue engineering technologies, and provide a holistic overview of the field. Techniques that can control the average spacing and clustering of cell adhesion ligands are well established and have been highly successful in describing cell adhesion and migration in 2D. Extension of these engineering tools to 3D biomaterials has created many new hydrogel and nanofiber scaffold technologies that are being used to design in vitro experiments with more physiologically relevant conditions. Researchers are beginning to study complex cell functions in 3D. However, there is a need for biomaterials systems that provide fine control over the nanoscale presentation of bioactive ligands in 3D. Additionally, there is a need for 2- and 3D techniques that can control the nanoscale presentation of multiple bioactive ligands and that can control the temporal changes in the cellular microenvironment. (topical review)

Visceral Congestion in Heart Failure: Right Ventricular Dysfunction, Splanchnic Hemodynamics, and the Intestinal Microenvironment.

Science.gov (United States)

Polsinelli, Vincenzo B; Sinha, Arjun; Shah, Sanjiv J

2017-12-01

Visceral venous congestion of the gut may play a key role in the pathogenesis of right-sided heart failure (HF) and cardiorenal syndromes. Here, we review the role of right ventricular (RV) dysfunction, visceral congestion, splanchnic hemodynamics, and the intestinal microenvironment in the setting of right-sided HF. We review recent literature on this topic, outline possible mechanisms of disease pathogenesis, and discuss potential therapeutics. There are several mechanisms linking RV-gut interactions via visceral venous congestion which could result in (1) hypoxia and acidosis in enterocytes, which may lead to enhanced sodium-hydrogen exchanger 3 (NHE3) expression with increased sodium and fluid retention; (2) decreased luminal pH in the intestines, which could lead to alteration of the gut microbiome which could increase gut permeability and inflammation; (3) alteration of renal hemodynamics with triggering of the cardiorenal syndrome; and (4) altered phosphate metabolism resulting in increased pulmonary artery stiffening, thereby increasing RV afterload. A wide variety of therapeutic interventions that act on the RV, pulmonary vasculature, intestinal microenvironment, and the kidney could alter these pathways and should be tested in patients with right-sided HF. The RV-gut axis is an important aspect of HF pathogenesis that deserves more attention. Modulation of the pathways interconnecting the right heart, visceral congestion, and the intestinal microenvironment could be a novel avenue of intervention for right-sided HF.

Immunological Dysregulation in Multiple Myeloma Microenvironment

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Romano, Alessandra; Conticello, Concetta; Cavalli, Maide; Vetro, Calogero; La Fauci, Alessia; Parrinello, Nunziatina Laura; Di Raimondo, Francesco

2014-01-01

Multiple Myeloma (MM) is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extr...

Multiparametric classification links tumor microenvironments with tumor cell phenotype.

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Bojana Gligorijevic

2014-11-01

Full Text Available While it has been established that a number of microenvironment components can affect the likelihood of metastasis, the link between microenvironment and tumor cell phenotypes is poorly understood. Here we have examined microenvironment control over two different tumor cell motility phenotypes required for metastasis. By high-resolution multiphoton microscopy of mammary carcinoma in mice, we detected two phenotypes of motile tumor cells, different in locomotion speed. Only slower tumor cells exhibited protrusions with molecular, morphological, and functional characteristics associated with invadopodia. Each region in the primary tumor exhibited either fast- or slow-locomotion. To understand how the tumor microenvironment controls invadopodium formation and tumor cell locomotion, we systematically analyzed components of the microenvironment previously associated with cell invasion and migration. No single microenvironmental property was able to predict the locations of tumor cell phenotypes in the tumor if used in isolation or combined linearly. To solve this, we utilized the support vector machine (SVM algorithm to classify phenotypes in a nonlinear fashion. This approach identified conditions that promoted either motility phenotype. We then demonstrated that varying one of the conditions may change tumor cell behavior only in a context-dependent manner. In addition, to establish the link between phenotypes and cell fates, we photoconverted and monitored the fate of tumor cells in different microenvironments, finding that only tumor cells in the invadopodium-rich microenvironments degraded extracellular matrix (ECM and disseminated. The number of invadopodia positively correlated with degradation, while the inhibiting metalloproteases eliminated degradation and lung metastasis, consistent with a direct link among invadopodia, ECM degradation, and metastasis. We have detected and characterized two phenotypes of motile tumor cells in vivo, which

[Prostate cancer microenvironment: Its structure, functions and therapeutic applications].

Science.gov (United States)

Lorion, R; Bladou, F; Spatz, A; van Kempen, L; Irani, J

2016-06-01

In the field of prostate cancer there is a growing tendency for more and more studies to emphasise the predominant role of the zone situated between the tumour and the host: the tumour microenvironment. The aim of this article is to describe the structure and the functions of the prostate cancer microenvironment as well as the principal treatments that are being applied to it. PubMed and ScienceDirect databases have been interrogated using the association of keywords "tumour microenvironment" and "neoplasm therapy" along with "microenvironnement tumoral" and "traitements". Of the 593 articles initially found, 50 were finally included. The tumour microenvironment principally includes host elements that are diverted from their primary functions and encourage the development of the tumour. In it we find immunity cells, support tissue as well as vascular and lymphatic neovascularization. Highlighting the major role played by this microenvironment has led to the development of specific treatments, notably antiangiogenic therapy and immunotherapy. The tumour microenvironment, the tumour and the host influence themselves mutually and create a variable situation over time. Improvement of the knowledge of the prostate cancer microenvironment gradually enables us to pass from an approach centred on the tumour to a broader approach to the whole tumoral ecosystem. This enabled the emergence of new treatments whose place in the therapeutic arsenal still need to be found. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Microenvironment-Centred Dynamics in Aggressive B-Cell Lymphomas

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Matilde Cacciatore

2012-01-01

Full Text Available Aggressive B-cell lymphomas share high proliferative and invasive attitudes and dismal prognosis despite heterogeneous biological features. In the interchained sequence of events leading to cancer progression, neoplastic clone-intrinsic molecular events play a major role. Nevertheless, microenvironment-related cues have progressively come into focus as true determinants for this process. The cancer-associated microenvironment is a complex network of nonneoplastic immune and stromal cells embedded in extracellular components, giving rise to a multifarious crosstalk with neoplastic cells towards the induction of a supportive milieu. The immunological and stromal microenvironments have been classically regarded as essential partners of indolent lymphomas, while considered mainly negligible in the setting of aggressive B-cell lymphomas that, by their nature, are less reliant on external stimuli. By this paper we try to delineate the cardinal microenvironment-centred dynamics exerting an influence over lymphoid clone progression in aggressive B-cell lymphomas.

Tumor microenvironment indoctrination: an emerging hallmark of cancer.

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Goetz, Jacky G

2012-01-01

Nastiness of cancer does not only reside in the corruption of cancer cells by genetic aberrations that drive their sustained proliferative power--the roots of malignancy--but also in its aptitude to reciprocally sculpt its surrounding environment and cellular stromal ecosystem, in such a way that the corrupted tumor microenvironment becomes a full pro-tumorigenic entity. Such a contribution had been appreciated three decades ago already, with the discovery of tumor angiogenesis and extracellular matrix remodeling. Nevertheless, the recent emergence of the tumor microenvironment as the critical determinant in cancer biology is paralleled by the promising therapeutic potential it carries, opening alternate routes to fight cancer. The study of the tumor microenvironment recruited numerous lead-scientists over the years, with distinct perspectives, and some of them have kindly accepted to contribute to the elaboration of this special issue entitled Tumor microenvironment indoctrination: An emerging hallmark of cancer.

Milestones in software engineering and knowledge engineering history: a comparative review.

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del Águila, Isabel M; Palma, José; Túnez, Samuel

2014-01-01

We present a review of the historical evolution of software engineering, intertwining it with the history of knowledge engineering because "those who cannot remember the past are condemned to repeat it." This retrospective represents a further step forward to understanding the current state of both types of engineerings; history has also positive experiences; some of them we would like to remember and to repeat. Two types of engineerings had parallel and divergent evolutions but following a similar pattern. We also define a set of milestones that represent a convergence or divergence of the software development methodologies. These milestones do not appear at the same time in software engineering and knowledge engineering, so lessons learned in one discipline can help in the evolution of the other one.

Engineering the hematopoietic stem cell niche: Frontiers in biomaterial science

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Choi, Ji Sun; Mahadik, Bhushan P.; Harley, Brendan A. C.

2016-01-01

Hematopoietic stem cells (HSCs) play a crucial role in the generation of the body’s blood and immune cells. This process takes place primarily in the bone marrow in specialized ‘niche’ microenvironments, which provide signals responsible for maintaining a balance between HSC quiescence, self-renewal, and lineage specification required for life-long hematopoiesis. While our understanding of these signaling mechanisms continues to improve, our ability to engineer them in vitro for the expansion of clinically relevant HSC populations is still lacking. In this review, we focus on development of biomaterials-based culture platforms for in vitro study of interactions between HSCs and their local microenvironment. The tools and techniques used for both examining HSC-niche interactions as well as applying these findings towards controlled HSC expansion or directed differentiation in 2D and 3D platforms are discussed. These novel techniques hold the potential to push the existing boundaries of HSC cultures towards high-throughput, real-time, and single-cell level biomimetic approaches that enable a more nuanced understanding of HSC regulation and function. Their application in conjunction with innovative biomaterial platforms can pave the way for engineering artificial bone marrow niches for clinical applications as well as elucidating the pathology of blood-related cancers and disorders. PMID:26356030

Targeting Gas6/TAM in cancer cells and tumor microenvironment.

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Wu, Guiling; Ma, Zhiqiang; Cheng, Yicheng; Hu, Wei; Deng, Chao; Jiang, Shuai; Li, Tian; Chen, Fulin; Yang, Yang

2018-01-31

Growth arrest-specific 6, also known as Gas6, is a human gene encoding the Gas6 protein, which was originally found to be upregulated in growth-arrested fibroblasts. Gas6 is a member of the vitamin K-dependent family of proteins expressed in many human tissues and regulates several biological processes in cells, including proliferation, survival and migration, by binding to its receptors Tyro3, Axl and Mer (TAM). In recent years, the roles of Gas6/TAM signalling in cancer cells and the tumour microenvironment have been studied, and some progress has made in targeted therapy, providing new potential directions for future investigations of cancer treatment. In this review, we introduce the Gas6 and TAM receptors and describe their involvement in different cancers and discuss the roles of Gas6 in cancer cells, the tumour microenvironment and metastasis. Finally, we introduce recent studies on Gas6/TAM targeting in cancer therapy, which will assist in the experimental design of future analyses and increase the potential use of Gas6 as a therapeutic target for cancer.

Milestones in Software Engineering and Knowledge Engineering History: A Comparative Review

Science.gov (United States)

del Águila, Isabel M.; Palma, José; Túnez, Samuel

2014-01-01

We present a review of the historical evolution of software engineering, intertwining it with the history of knowledge engineering because “those who cannot remember the past are condemned to repeat it.” This retrospective represents a further step forward to understanding the current state of both types of engineerings; history has also positive experiences; some of them we would like to remember and to repeat. Two types of engineerings had parallel and divergent evolutions but following a similar pattern. We also define a set of milestones that represent a convergence or divergence of the software development methodologies. These milestones do not appear at the same time in software engineering and knowledge engineering, so lessons learned in one discipline can help in the evolution of the other one. PMID:24624046

Bioengineering Embryonic Stem Cell Microenvironments for the Study of Breast Cancer

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Yubing Xie

2011-11-01

Full Text Available Breast cancer is the most prevalent disease amongst women worldwide and metastasis is the main cause of death due to breast cancer. Metastatic breast cancer cells and embryonic stem (ES cells display similar characteristics. However, unlike metastatic breast cancer cells, ES cells are nonmalignant. Furthermore, embryonic microenvironments have the potential to convert metastatic breast cancer cells into a less invasive phenotype. The creation of in vitro embryonic microenvironments will enable better understanding of ES cell-breast cancer cell interactions, help elucidate tumorigenesis, and lead to the restriction of breast cancer metastasis. In this article, we will present the characteristics of breast cancer cells and ES cells as well as their microenvironments, importance of embryonic microenvironments in inhibiting tumorigenesis, convergence of tumorigenic and embryonic signaling pathways, and state of the art in bioengineering embryonic microenvironments for breast cancer research. Additionally, the potential application of bioengineered embryonic microenvironments for the prevention and treatment of invasive breast cancer will be discussed.

Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study Cancer-Microenvironment Interactions?

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Jessica Hoarau-Véchot

2018-01-01

Full Text Available An area that has come to be of tremendous interest in tumor research in the last decade is the role of the microenvironment in the biology of neoplastic diseases. The tumor microenvironment (TME comprises various cells that are collectively important for normal tissue homeostasis as well as tumor progression or regression. Seminal studies have demonstrated the role of the dialogue between cancer cells (at many sites and the cellular component of the microenvironment in tumor progression, metastasis, and resistance to treatment. Using an appropriate system of microenvironment and tumor culture is the first step towards a better understanding of the complex interaction between cancer cells and their surroundings. Three-dimensional (3D models have been widely described recently. However, while it is claimed that they can bridge the gap between in vitro and in vivo, it is sometimes hard to decipher their advantage or limitation compared to classical two-dimensional (2D cultures, especially given the broad number of techniques used. We present here a comprehensive review of the different 3D methods developed recently, and, secondly, we discuss the pros and cons of 3D culture compared to 2D when studying interactions between cancer cells and their microenvironment.

Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study Cancer-Microenvironment Interactions?

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Hoarau-Véchot, Jessica; Rafii, Arash; Touboul, Cyril; Pasquier, Jennifer

2018-01-18

An area that has come to be of tremendous interest in tumor research in the last decade is the role of the microenvironment in the biology of neoplastic diseases. The tumor microenvironment (TME) comprises various cells that are collectively important for normal tissue homeostasis as well as tumor progression or regression. Seminal studies have demonstrated the role of the dialogue between cancer cells (at many sites) and the cellular component of the microenvironment in tumor progression, metastasis, and resistance to treatment. Using an appropriate system of microenvironment and tumor culture is the first step towards a better understanding of the complex interaction between cancer cells and their surroundings. Three-dimensional (3D) models have been widely described recently. However, while it is claimed that they can bridge the gap between in vitro and in vivo, it is sometimes hard to decipher their advantage or limitation compared to classical two-dimensional (2D) cultures, especially given the broad number of techniques used. We present here a comprehensive review of the different 3D methods developed recently, and, secondly, we discuss the pros and cons of 3D culture compared to 2D when studying interactions between cancer cells and their microenvironment.

Microcapsule Technology for Controlled Growth Factor Release in Musculoskeletal Tissue Engineering.

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Della Porta, Giovanna; Ciardulli, Maria C; Maffulli, Nicola

2018-06-01

Tissue engineering strategies have relied on engineered 3-dimensional (3D) scaffolds to provide architectural templates that can mimic the native cell environment. Among the several technologies proposed for the fabrication of 3D scaffold, that can be attractive for stem cell cultivation and differentiation, moulding or bioplotting of hydrogels allow the stratification of layers loaded with cells and with specific additives to obtain a predefined microstructural organization. Particularly with bioplotting technology, living cells, named bio-ink, and additives, such as biopolymer microdevices/nanodevices for the controlled delivery of growth factors or biosignals, can be organized spatially into a predesigned 3D pattern by automated fabrication with computer-aided digital files. The technologies for biopolymer microcarrier/nanocarrier fabrication can be strategic to provide a controlled spatiotemporal delivery of specific biosignals within a microenvironment that can better or faster address the stem cells loaded within it. In this review, some examples of growth factor-controlled delivery by biopolymer microdevices/nanodevices embedded within 3D hydrogel scaffolds will be described, to achieve a bioengineered 3D interactive microenvironment for stem cell differentiation. Conventional and recently proposed technologies for biopolymer microcapsule fabrication for controlled delivery over several days will also be illustrated and critically discussed.

The JSC Engineering Directorate Product Peer Review Process

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Jenks, Kenneth C.

2009-01-01

The JSC Engineering Directorate has developed a Product Peer Review process in support of NASA policies for project management and systems engineering. The process complies with the requirements of NPR 7120.5, NPR 7123.1 and NPR 7150.2 and follows the guidance in NASA/SP-2007-6105. This presentation will give an overview of the process followed by a brief demonstration of an actual peer review, with audience participation.

A Study of Technical Engineering Peer Reviews at NASA

Science.gov (United States)

Chao, Lawrence P.; Tumer, Irem Y.; Bell, David G.

2003-01-01

This report describes the state of practices of design reviews at NASA and research into what can be done to improve peer review practices. There are many types of reviews at NASA: required and not, formalized and informal, programmatic and technical. Standing project formal reviews such as the Preliminary Design Review and Critical Design Review are a required part of every project and mission development. However, the technical, engineering peer reviews that support teams' work on such projects are informal, some times ad hoc, and inconsistent across the organization. The goal of this work is to identify best practices and lessons learned from NASA's experience, supported by academic research and methodologies to ultimately improve the process. This research has determined that the organization, composition, scope, and approach of the reviews impact their success. Failure Modes and Effects Analysis (FMEA) can identify key areas of concern before or in the reviews. Product definition tools like the Project Priority Matrix, engineering-focused Customer Value Chain Analysis (CVCA), and project or system-based Quality Function Deployment (QFD) help prioritize resources in reviews. The use of information technology and structured design methodologies can strengthen the engineering peer review process to help NASA work towards error-proofing the design process.

Co-culture systems-based strategies for articular cartilage tissue engineering.

Science.gov (United States)

Zhang, Yu; Guo, Weimin; Wang, Mingjie; Hao, Chunxiang; Lu, Liang; Gao, Shuang; Zhang, Xueliang; Li, Xu; Chen, Mingxue; Li, Penghao; Jiang, Peng; Lu, Shibi; Liu, Shuyun; Guo, Quanyi

2018-03-01

Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering. © 2017 Wiley Periodicals, Inc.

Microtissues in Cardiovascular Medicine: Regenerative Potential Based on a 3D Microenvironment

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Julia Günter

2016-01-01

Full Text Available More people die annually from cardiovascular diseases than from any other cause. In particular, patients who suffer from myocardial infarction may be affected by ongoing adverse remodeling processes of the heart that may ultimately lead to heart failure. The introduction of stem and progenitor cell-based applications has raised substantial hope for reversing these processes and inducing cardiac regeneration. However, current stem cell therapies using single-cell suspensions have failed to demonstrate long-lasting efficacy due to the overall low retention rate after cell delivery to the myocardium. To overcome this obstacle, the concept of 3D cell culture techniques has been proposed to enhance therapeutic efficacy and cell engraftment based on the simulation of an in vivo-like microenvironment. Of great interest is the use of so-called microtissues or spheroids, which have evolved from their traditional role as in vitro models to their novel role as therapeutic agents. This review will provide an overview of the therapeutic potential of microtissues by addressing primarily cardiovascular regeneration. It will accentuate their advantages compared to other regenerative approaches and summarize the methods for generating clinically applicable microtissues. In addition, this review will illustrate the unique properties of the microenvironment within microtissues that makes them a promising next-generation therapeutic approach.

Of Microenvironments and Mammary Stem Cells

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LaBarge, Mark A; Petersen, Ole W; Bissell, Mina J

2007-06-01

In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit.

Trabectedin and Plitidepsin: Drugs from the Sea that Strike the Tumor Microenvironment

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Carlos M. Galmarini

2014-01-01

Full Text Available The prevailing paradigm states that cancer cells acquire multiple genetic mutations in oncogenes or tumor suppressor genes whose respective activation/up-regulation or loss of function serve to impart aberrant properties, such as hyperproliferation or inhibition of cell death. However, a tumor is now considered as an organ-like structure, a complex system composed of multiple cell types (e.g., tumor cells, inflammatory cells, endothelial cells, fibroblasts, etc. all embedded in an inflammatory stroma. All these components influence each other in a complex and dynamic cross-talk, leading to tumor cell survival and progression. As the microenvironment has such a crucial role in tumor pathophysiology, it represents an attractive target for cancer therapy. In this review, we describe the mechanism of action of trabectedin and plitidepsin as an example of how these specific drugs of marine origin elicit their antitumor activity not only by targeting tumor cells but also the tumor microenvironment.

Neurophysiology and neural engineering: a review.

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Prochazka, Arthur

2017-08-01

Neurophysiology is the branch of physiology concerned with understanding the function of neural systems. Neural engineering (also known as neuroengineering) is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, enhance, or otherwise exploit the properties and functions of neural systems. In most cases neural engineering involves the development of an interface between electronic devices and living neural tissue. This review describes the origins of neural engineering, the explosive development of methods and devices commencing in the late 1950s, and the present-day devices that have resulted. The barriers to interfacing electronic devices with living neural tissues are many and varied, and consequently there have been numerous stops and starts along the way. Representative examples are discussed. None of this could have happened without a basic understanding of the relevant neurophysiology. I also consider examples of how neural engineering is repaying the debt to basic neurophysiology with new knowledge and insight. Copyright © 2017 the American Physiological Society.

Value-Engineering Review for Numerical Control

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Warner, J. L.

1984-01-01

Selecting parts for conversion from conventional machining to numerical control, value-engineering review performed for every part to identify potential changes to part design that result in increased production efficiency.

Tumor Engineering: The Other Face of Tissue Engineering

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Ghajar, Cyrus M; Bissell, Mina J

2010-03-09

Advances in tissue engineering have been accomplished for years by employing biomimetic strategies to provide cells with aspects of their original microenvironment necessary to reconstitute a unit of both form and function for a given tissue.We believe that the most critical hallmark of cancer is loss of integration of architecture and function; thus, it stands to reason that similar strategies could be employed to understand tumor biology. In this commentary, we discuss work contributed by Fischbach-Teschl and colleagues to this special issue of Tissue Engineering in the context of 'tumor engineering', that is, the construction of complex cell culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. We provide examples of fundamental questions that could be answered by developing such models, and encourage the continued collaboration between physical scientists and life scientists not only for regenerative purposes, but also to unravel the complexity that is the tumor microenvironment. In 1993, Vacanti and Langer cast a spotlight on the growing gap between patients in need of organ transplants and the amount of available donor organs; they reaffirmed that tissue engineering could eventually address this problem by 'applying principles of engineering and the life sciences toward the development of biological substitutes. Mortality figures and direct health care costs for cancer patients rival those of patients who experience organ failure. Cancer is the second leading cause of death in the United States (Source: American Cancer Society) and it is estimated that direct medical costs for cancer patients approach $100B yearly in the United States alone (Source: National Cancer Institute). In addition, any promising therapy that emerges from the laboratory costs roughly $1.7B to take from bench to bedside. Whereas we have indeed waged war on

Tumor Biology and Microenvironment Research

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Part of NCI's Division of Cancer Biology's research portfolio, research in this area seeks to understand the role of tumor cells and the tumor microenvironment (TME) in driving cancer initiation, progression, maintenance and recurrence.

Fabrication of scaffolds in tissue engineering: A review

Science.gov (United States)

Zhao, Peng; Gu, Haibing; Mi, Haoyang; Rao, Chengchen; Fu, Jianzhong; Turng, Lih-sheng

2018-03-01

Tissue engineering (TE) is an integrated discipline that involves engineering and natural science in the development of biological materials to replace, repair, and improve the function of diseased or missing tissues. Traditional medical and surgical treatments have been reported to have side effects on patients caused by organ necrosis and tissue loss. However, engineered tissues and organs provide a new way to cure specific diseases. Scaffold fabrication is an important step in the TE process. This paper summarizes and reviews the widely used scaffold fabrication methods, including conventional methods, electrospinning, three-dimensional printing, and a combination of molding techniques. Furthermore, the differences among the properties of tissues, such as pore size and distribution, porosity, structure, and mechanical properties, are elucidated and critically reviewed. Some studies that combine two or more methods are also reviewed. Finally, this paper provides some guidance and suggestions for the future of scaffold fabrication.

Combined Effects of Pericytes in the Tumor Microenvironment

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Aline Lopes Ribeiro

2015-01-01

Full Text Available Pericytes are multipotent perivascular cells whose involvement in vasculature development is well established. Evidences in the literature also suggest that pericytes display immune properties and that these cells may serve as an in vivo reservoir of stem cells, contributing to the regeneration of diverse tissues. Pericytes are also capable of tumor homing and are important cellular components of the tumor microenvironment (TME. In this review, we highlight the contribution of pericytes to some classical hallmarks of cancer, namely, tumor angiogenesis, growth, metastasis, and evasion of immune destruction, and discuss how collectively these hallmarks could be tackled by therapies targeting pericytes, providing a rationale for cancer drugs aiming at the TME.

Emerging Roles for Eosinophils in the Tumor Microenvironment.

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Reichman, Hadar; Karo-Atar, Danielle; Munitz, Ariel

2016-11-01

Eosinophils are evolutionary conserved cells largely studied in the context of allergy. Although eosinophils were first described in tumors more than 120 years ago, their roles in cancer are often overlooked. This is puzzling given their potent immune modulatory, cytotoxic, and/or tissue repair capabilities, and recent studies demonstrating key roles for eosinophils in contexts far beyond their 'classical' field (e.g., metabolism, thermogenesis, and tissue regeneration). Recent data suggest that this frequently ignored cell is emerging as a potent immune effector and immune modulator in the tumor microenvironment. This review discusses the relevance of eosinophils to tumorigenesis and the potential to harness their function in cancer therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells.

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Sadtler, Kaitlyn; Estrellas, Kenneth; Allen, Brian W; Wolf, Matthew T; Fan, Hongni; Tam, Ada J; Patel, Chirag H; Luber, Brandon S; Wang, Hao; Wagner, Kathryn R; Powell, Jonathan D; Housseau, Franck; Pardoll, Drew M; Elisseeff, Jennifer H

2016-04-15

Immune-mediated tissue regeneration driven by a biomaterial scaffold is emerging as an innovative regenerative strategy to repair damaged tissues. We investigated how biomaterial scaffolds shape the immune microenvironment in traumatic muscle wounds to improve tissue regeneration. The scaffolds induced a pro-regenerative response, characterized by an mTOR/Rictor-dependent T helper 2 pathway that guides interleukin-4-dependent macrophage polarization, which is critical for functional muscle recovery. Manipulating the adaptive immune system using biomaterials engineering may support the development of therapies that promote both systemic and local pro-regenerative immune responses, ultimately stimulating tissue repair. Copyright © 2016, American Association for the Advancement of Science.

Cancer stem cells and the tumor microenvironment: interplay in tumor heterogeneity.

Science.gov (United States)

Albini, Adriana; Bruno, Antonino; Gallo, Cristina; Pajardi, Giorgio; Noonan, Douglas M; Dallaglio, Katiuscia

2015-01-01

Tumor cells able to recapitulate tumor heterogeneity have been tracked, isolated and characterized in different tumor types, and are commonly named Cancer Stem Cells or Cancer Initiating Cells (CSC/CIC). CSC/CIC are disseminated in the tumor mass and are resistant to anti-cancer therapies and adverse conditions. They are able to divide into another stem cell and a "proliferating" cancer cell. They appear to be responsible for disease recurrence and metastatic dissemination even after apparent eradication of the primary tumor. The modulation of CSC/CIC activities by the tumor microenvironment (TUMIC) is still poorly known. CSC/CIC may mutually interact with the TUMIC in a special and unique manner depending on the TUMIC cells or proteins encountered. The TUMIC consists of extracellular matrix components as well as cellular players among which endothelial, stromal and immune cells, providing and responding to signals to/from the CSC/CIC. This interplay can contribute to the mechanisms through which CSC/CIC may reside in a dormant state in a tissue for years, later giving rise to tumor recurrence or metastasis in patients. Different TUMIC components, including the connective tissue, can differentially activate CIC/CSC in different areas of a tumor and contribute to the generation of cancer heterogeneity. Here, we review possible networking activities between the different components of the tumor microenvironment and CSC/CIC, with a focus on its role in tumor heterogeneity and progression. We also summarize novel therapeutic options that could target both CSC/CIC and the microenvironment to elude resistance mechanisms activated by CSC/CIC, responsible for disease recurrence and metastases.

Development and characterization of a microfluidic model of the tumour microenvironment.

Science.gov (United States)

Ayuso, Jose M; Virumbrales-Muñoz, María; Lacueva, Alodia; Lanuza, Pilar M; Checa-Chavarria, Elisa; Botella, Pablo; Fernández, Eduardo; Doblare, Manuel; Allison, Simon J; Phillips, Roger M; Pardo, Julián; Fernandez, Luis J; Ochoa, Ignacio

2016-10-31

The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in real-time. The versatility of this microfluidic platform allows for different aspects of the microenvironment to be monitored and dissected. This is exemplified here by real-time profiling of oxygen and glucose concentrations inside the device as well as effects on cell proliferation and growth, ROS generation and apoptosis. Heterotypic cell interactions were also studied. The device provides a live 'window' into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data is presented for this indicating the device's potential to enable more physiological in vitro drug screening.

Ethical Risk Management Education in Engineering: A Systematic Review.

Science.gov (United States)

Guntzburger, Yoann; Pauchant, Thierry C; Tanguy, Philippe A

2017-04-01

Risk management is certainly one of the most important professional responsibilities of an engineer. As such, this activity needs to be combined with complex ethical reflections, and this requirement should therefore be explicitly integrated in engineering education. In this article, we analyse how this nexus between ethics and risk management is expressed in the engineering education research literature. It was done by reviewing 135 articles published between 1980 and March 1, 2016. These articles have been selected from 21 major journals that specialize in engineering education, engineering ethics and ethics education. Our review suggests that risk management is mostly used as an anecdote or an example when addressing ethics issues in engineering education. Further, it is perceived as an ethical duty or requirement, achieved through rational and technical methods. However, a small number of publications do offer some critical analyses of ethics education in engineering and their implications for ethical risk and safety management. Therefore, we argue in this article that the link between risk management and ethics should be further developed in engineering education in order to promote the progressive change toward more socially and environmentally responsible engineering practices. Several research trends and issues are also identified and discussed in order to support the engineering education community in this project.

Impact of the ovarian microenvironment on serous cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-14-1-0182 TITLE: Impact of the ovarian microenvironment on serous cancer PRINCIPAL INVESTIGATOR: Joanna E. Burdette...Impact of the ovarian microenvironment on serous cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0182 5c. PROGRAM ELEMENT NUMBER 6...for intervention that would block serous cancer while still confined to the fallopian tubes. Using a series of normal, modified, and tumorigenic tubal

A review of free-piston engine history and applications

Energy Technology Data Exchange (ETDEWEB)

Mikalsen, R.; Roskilly, A.P. [School of Marine Science and Technology, University of Newcastle upon Tyne, Newcastle upon Tyne NE1 7RU (United Kingdom)

2007-10-15

This document reviews the history of free-piston internal combustion engines, from the air compressors and gas generators used in the mid-20th century through to recent free-piston hydraulic engines and linear electric generators. Unique features of the free-piston engine are presented and their effects on engine operation are discussed, along with potential advantages and disadvantages compared to conventional engines. The paper focuses mainly on developed engines where operational data has been reported. Finally, the potential of the free-piston engine is evaluated and the most promising designs identified. (author)

Microenvironment is involved in cellular response to hydrostatic pressures during chondrogenesis of mesenchymal stem cells.

Science.gov (United States)

Ye, Rui; Hao, Jin; Song, Jinlin; Zhao, Zhihe; Fang, Shanbao; Wang, Yating; Li, Juan

2014-06-01

Chondrocytes integrate numerous microenvironmental cues to mount physiologically relevant differentiation responses, and the regulation of mechanical signaling in chondrogenic differentiation is now coming into intensive focus. To facilitate tissue-engineered chondrogenesis by mechanical strategy, a thorough understanding about the interactional roles of chemical factors under mechanical stimuli in regulating chondrogenesis is in great need. Therefore, this study attempts to investigate the interaction of rat MSCs with their microenvironment by imposing dynamic and static hydrostatic pressure through modulating gaseous tension above the culture medium. Under dynamic pressure, chemical parameters (pH, pO2, and pCO2) were kept in homeostasis. In contrast, pH was remarkably reduced due to increased pCO2 under static pressure. MSCs under the dynamically pressured microenvironment exhibited a strong accumulation of GAG within and outside the alginate beads, while cells under the statically pressured environment lost newly synthesized GAG into the medium with a speed higher than its production. In addition, the synergic influence on expression of chondrogenic genes was more persistent under dynamic pressure than that under static pressure. This temporal contrast was similar to that of activation of endogenous TGF-β1. Taken altogether, it indicates that a loading strategy which can keep a homeostatic chemical microenvironment is preferred, since it might sustain the stimulatory effects of mechanical stimuli on chondrogenesis via activation of endogenous TGF-β1. © 2013 Wiley Periodicals, Inc.

Spark ignition natural gas engines-A review

International Nuclear Information System (INIS)

Cho, Haeng Muk; He, Bang-Quan

2007-01-01

Natural gas is a promising alternative fuel to meet strict engine emission regulations in many countries. Natural gas engines can operate at lean burn and stoichiometric conditions with different combustion and emission characteristics. In this paper, the operating envelope, fuel economy, emissions, cycle-to-cycle variations in indicated mean effective pressure and strategies to achieve stable combustion of lean burn natural gas engines are highlighted. Stoichiometric natural gas engines are briefly reviewed. To keep the output power and torque of natural gas engines comparable to those of their gasoline or Diesel counterparts, high boost pressure should be used. High activity catalyst for methane oxidation and lean deNOx system or three way catalyst with precise air-fuel ratio control strategies should be developed to meet future stringent emission standards

Current Technologies Based on the Knowledge of the Stem Cells Microenvironments.

Science.gov (United States)

Mawad, Damia; Figtree, Gemma; Gentile, Carmine

2017-01-01

The stem cell microenvironment or niche plays a critical role in the regulation of survival, differentiation and behavior of stem cells and their progenies. Recapitulating each aspect of the stem cell niche is therefore essential for their optimal use in in vitro studies and in vivo as future therapeutics in humans. Engineering of optimal conditions for three-dimensional stem cell culture includes multiple transient and dynamic physiological stimuli, such as blood flow and tissue stiffness. Bioprinting and microfluidics technologies, including organs-on-a-chip, are among the most recent approaches utilized to replicate the three-dimensional stem cell niche for human tissue fabrication that allow the integration of multiple levels of tissue complexity, including blood flow. This chapter focuses on the physico-chemical and genetic cues utilized to engineer the stem cell niche and provides an overview on how both bioprinting and microfluidics technologies are improving our knowledge in this field for both disease modeling and tissue regeneration, including drug discovery and toxicity high-throughput assays and stem cell-based therapies in humans.

Plasticity of the Muscle Stem Cell Microenvironment.

Science.gov (United States)

Dinulovic, Ivana; Furrer, Regula; Handschin, Christoph

2017-01-01

Satellite cells (SCs) are adult muscle stem cells capable of repairing damaged and creating new muscle tissue throughout life. Their functionality is tightly controlled by a microenvironment composed of a wide variety of factors, such as numerous secreted molecules and different cell types, including blood vessels, oxygen, hormones, motor neurons, immune cells, cytokines, fibroblasts, growth factors, myofibers, myofiber metabolism, the extracellular matrix and tissue stiffness. This complex niche controls SC biology-quiescence, activation, proliferation, differentiation or renewal and return to quiescence. In this review, we attempt to give a brief overview of the most important players in the niche and their mutual interaction with SCs. We address the importance of the niche to SC behavior under physiological and pathological conditions, and finally survey the significance of an artificial niche both for basic and translational research purposes.

A review of decellularized stem cell matrix: a novel cell expansion system for cartilage tissue engineering

Directory of Open Access Journals (Sweden)

M Pei

2011-11-01

Full Text Available Cell-based therapy is a promising biological approach for the treatment of cartilage defects. Due to the small size of autologous cartilage samples available for cell transplantation in patients, cells need to be expanded to yield a sufficient cell number for cartilage repair. However, chondrocytes and adult stem cells tend to become replicatively senescent once they are expanded on conventional plastic flasks. Many studies demonstrate that the loss of cell properties is concomitant with the decreased cell proliferation capacity. This is a significant challenge for cartilage tissue engineering and regeneration. Despite much progress having been made in cell expansion, there are still concerns over expanded cell size and quality for cell transplantation applications. Recently, in vivo investigations in stem cell niches have suggested the importance of developing an in vitro stem cell microenvironment for cell expansion and tissue-specific differentiation. Our and other investigators’ work indicates that a decellularized stem cell matrix (DSCM may provide such an expansion system to yield large-quantity and high-quality cells for cartilage tissue engineering and regeneration. This review briefly introduces key parameters in an in vivo stem cell niche and focuses on our recent work on DSCM for its rejuvenating or reprograming effect on various adult stem cells and chondrocytes. Since research in DSCM is still in its infancy, we are only able to discuss some potential mechanisms of DSCM on cell proliferation and chondrogenic potential. Further investigations of the underlying mechanism and in vivo regeneration capacity will allow this approach to be used in clinics.

Nanoscale tissue engineering: spatial control over cell-materials interactions

Science.gov (United States)

Wheeldon, Ian; Farhadi, Arash; Bick, Alexander G.; Jabbari, Esmaiel; Khademhosseini, Ali

2011-01-01

Cells interact with the surrounding environment by making tens to hundreds of thousands of nanoscale interactions with extracellular signals and features. The goal of nanoscale tissue engineering is to harness the interactions through nanoscale biomaterials engineering in order to study and direct cellular behaviors. Here, we review the nanoscale tissue engineering technologies for both two- and three-dimensional studies (2- and 3D), and provide a holistic overview of the field. Techniques that can control the average spacing and clustering of cell adhesion ligands are well established and have been highly successful in describing cell adhesion and migration in 2D. Extension of these engineering tools to 3D biomaterials has created many new hydrogel and nanofiber scaffolds technologies that are being used to design in vitro experiments with more physiologically relevant conditions. Researchers are beginning to study complex cell functions in 3D, however, there is a need for biomaterials systems that provide fine control over the nanoscale presentation of bioactive ligands in 3D. Additionally, there is a need for 2- and 3D techniques that can control the nanoscale presentation of multiple bioactive ligands and the temporal changes in cellular microenvironment. PMID:21451238

Cellular immobilization within microfluidic microenvironments: dielectrophoresis with polyelectrolyte multilayers.

Science.gov (United States)

Forry, Samuel P; Reyes, Darwin R; Gaitan, Michael; Locascio, Laurie E

2006-10-25

The development of biomimetic microenvironments will improve cell culture techniques by enabling in vitro cell cultures that mimic in vivo behavior; however, experimental control over attachment, cellular position, or intercellular distances within such microenvironments remains challenging. We report here the rapid and controllable immobilization of suspended mammalian cells within microfabricated environments using a combination of electronic (dielectrophoresis, DEP) and chemical (polyelectrolyte multilayers, PEMS) forces. While cellular position within the microsystem is rapidly patterned via intermittent DEP trapping, persistent adhesion after removal of electronic forces is enabled by surface treatment with PEMS that are amenable to cellular attachment. In contrast to DEP trapping alone, persistent adhesion enables the soluble microenvironment to be systematically varied, facilitating the use of soluble probes of cell state and enabling cellular characterization in response to various soluble stimuli.

Straight vegetable oils usage in a compression ignition engine - A review

Energy Technology Data Exchange (ETDEWEB)

Misra, R.D.; Murthy, M.S. [Mechanical Engineering Department, National Institute of Technology, Silchar 788010, Assam (India)

2010-12-15

The ever increasing fossil fuel usage and cost, environmental concern has forced the world to look for alternatives. Straight vegetable oils in compression ignition engine are a ready solution available, however, with certain limitations and with some advantages as reported by many researchers. A comprehensive and critical review is presented specifically pertaining to straight vegetable oils usage in diesel engine. A detailed record of historical events described. Research carried out specifically under Indian conditions and international research work on the usage of straight vegetable oils in the diesel engine is separately reviewed. Many researchers have reported that straight vegetable oils in small percentage blends with diesel when used lower capacity diesel engines have shown great promise with regards to the thermal performance as well exhaust emissions. This has been explained in detail. Finally based on the review of international as well as Indian research a SWOT analysis is carried out. The review concludes that there is still scope for research in this area. (author)

Microenvironments and microscale productivity of cyanobacterial desert crusts

Science.gov (United States)

Garcia-Pichel, F.; Belnap, Jayne

1996-01-01

We used microsensors to characterize physicochemical microenvironments and photosynthesis occurring immediately after water saturation in two desert soil crusts from southeastern Utah, which were formed by the cyanobacteria Microcoleus vaginatus Gomont, Nostoc spp., and Scytonema sp. The light fields within the crusts presented steep vertical gradients in magnitude and spectral composition. Near-surface light-trapping zones were formed due to the scattering nature of the sand particles, but strong light attenuation resulted in euphotic zones only ca. 1 mm deep, which were progressively enriched in longer wavelengths with depth. Rates of gross photosynthesis (3.4a??9.4 mmol O2A?ma??2A?ha??1) and dark respiration (0.81a??3.1 mmol Oa??2A?ma??2A?ha??1) occurring within 1 to several mm from the surface were high enough to drive the formation of marked oxygen microenvironments that ranged from oxygen supersaturation to anoxia. The photosynthetic activity also resulted in localized pH values in excess of 10, 2a??3 units above the soil pH. Differences in metabolic parameters and community structure between two types of crusts were consistent with a successional pattern, which could be partially explained on the basis of the microenvironments. We discuss the significance of high metabolic rates and the formation of microenvironments for the ecology of desert crusts, as well as the advantages and limitations of microsensor-based methods for crust investigation.

Cancer Stem Cells and Their Microenvironment: Biology and Therapeutic Implications

Directory of Open Access Journals (Sweden)

Eunice Yuen-Ting Lau

2017-01-01

Full Text Available Tumor consists of heterogeneous cancer cells including cancer stem cells (CSCs that can terminally differentiate into tumor bulk. Normal stem cells in normal organs regulate self-renewal within a stem cell niche. Likewise, accumulating evidence has also suggested that CSCs are maintained extrinsically within the tumor microenvironment, which includes both cellular and physical factors. Here, we review the significance of stromal cells, immune cells, extracellular matrix, tumor stiffness, and hypoxia in regulation of CSC plasticity and therapeutic resistance. With a better understanding of how CSC interacts with its niche, we are able to identify potential therapeutic targets for the development of more effective treatments against cancer.

Engineering and physical sciences in oncology: challenges and opportunities.

Science.gov (United States)

Mitchell, Michael J; Jain, Rakesh K; Langer, Robert

2017-11-01

The principles of engineering and physics have been applied to oncology for nearly 50 years. Engineers and physical scientists have made contributions to all aspects of cancer biology, from quantitative understanding of tumour growth and progression to improved detection and treatment of cancer. Many early efforts focused on experimental and computational modelling of drug distribution, cell cycle kinetics and tumour growth dynamics. In the past decade, we have witnessed exponential growth at the interface of engineering, physics and oncology that has been fuelled by advances in fields including materials science, microfabrication, nanomedicine, microfluidics, imaging, and catalysed by new programmes at the National Institutes of Health (NIH), including the National Institute of Biomedical Imaging and Bioengineering (NIBIB), Physical Sciences in Oncology, and the National Cancer Institute (NCI) Alliance for Nanotechnology. Here, we review the advances made at the interface of engineering and physical sciences and oncology in four important areas: the physical microenvironment of the tumour and technological advances in drug delivery; cellular and molecular imaging; and microfluidics and microfabrication. We discussthe research advances, opportunities and challenges for integrating engineering and physical sciences with oncology to develop new methods to study, detect and treat cancer, and we also describe the future outlook for these emerging areas.

Engineered Proteins Program Mammalian Cells to Target Inflammatory Disease Sites.

Science.gov (United States)

Qudrat, Anam; Mosabbir, Abdullah Al; Truong, Kevin

2017-06-22

Disease sites in atherosclerosis and cancer feature cell masses (e.g., plaques/tumors), a low pH extracellular microenvironment, and various pro-inflammatory cytokines such as tumor necrosis factor α (TNFα). The ability to engineer a cell to seek TNFα sources allows for targeted therapeutic delivery. To accomplish this, here we introduced a system of proteins: an engineered TNFα chimeric receptor (named TNFR1chi), a previously engineered Ca 2+ -activated RhoA (named CaRQ), vesicular stomatitis virus glycoprotein G (VSVG), and thymidine kinase. Upon binding TNFα, TNFR1chi generates a Ca 2+ signal that in turn activates CaRQ-mediated non-apoptotic blebs that allow migration toward the TNFα source. Next, the addition of VSVG, upon low pH induction, causes membrane fusion of the engineered and TNFα source cells. Finally, after ganciclovir treatment cells undergo death via the thymidine kinase suicide mechanism. Hence, we assembled a system of proteins that forms the basis of engineering a cell to target inflammatory disease sites characterized by TNFα secretion and a low-pH microenvironment. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of the tissue microenvironment in the regulation of cancer cell motility and invasion

Directory of Open Access Journals (Sweden)

Brábek Jan

2010-09-01

Full Text Available Abstract During malignant neoplastic progression the cells undergo genetic and epigenetic cancer-specific alterations that finally lead to a loss of tissue homeostasis and restructuring of the microenvironment. The invasion of cancer cells through connective tissue is a crucial prerequisite for metastasis formation. Although cell invasion is foremost a mechanical process, cancer research has focused largely on gene regulation and signaling that underlie uncontrolled cell growth. More recently, the genes and signals involved in the invasion and transendothelial migration of cancer cells, such as the role of adhesion molecules and matrix degrading enzymes, have become the focus of research. In this review we discuss how the structural and biomechanical properties of extracellular matrix and surrounding cells such as endothelial cells influence cancer cell motility and invasion. We conclude that the microenvironment is a critical determinant of the migration strategy and the efficiency of cancer cell invasion.

Multimodal imaging of lung cancer and its microenvironment (Conference Presentation)

Science.gov (United States)

Hariri, Lida P.; Niederst, Matthew J.; Mulvey, Hillary; Adams, David C.; Hu, Haichuan; Chico Calero, Isabel; Szabari, Margit V.; Vakoc, Benjamin J.; Hasan, Tayyaba; Bouma, Brett E.; Engelman, Jeffrey A.; Suter, Melissa J.

2016-03-01

Despite significant advances in targeted therapies for lung cancer, nearly all patients develop drug resistance within 6-12 months and prognosis remains poor. Developing drug resistance is a progressive process that involves tumor cells and their microenvironment. We hypothesize that microenvironment factors alter tumor growth and response to targeted therapy. We conducted in vitro studies in human EGFR-mutant lung carcinoma cells, and demonstrated that factors secreted from lung fibroblasts results in increased tumor cell survival during targeted therapy with EGFR inhibitor, gefitinib. We also demonstrated that increased environment stiffness results in increased tumor survival during gefitinib therapy. In order to test our hypothesis in vivo, we developed a multimodal optical imaging protocol for preclinical intravital imaging in mouse models to assess tumor and its microenvironment over time. We have successfully conducted multimodal imaging of dorsal skinfold chamber (DSC) window mice implanted with GFP-labeled human EGFR mutant lung carcinoma cells and visualized changes in tumor development and microenvironment facets over time. Multimodal imaging included structural OCT to assess tumor viability and necrosis, polarization-sensitive OCT to measure tissue birefringence for collagen/fibroblast detection, and Doppler OCT to assess tumor vasculature. Confocal imaging was also performed for high-resolution visualization of EGFR-mutant lung cancer cells labeled with GFP, and was coregistered with OCT. Our results demonstrated that stromal support and vascular growth are essential to tumor progression. Multimodal imaging is a useful tool to assess tumor and its microenvironment over time.

Microenvironment Determinants of Brain Metastasis

Directory of Open Access Journals (Sweden)

Zhang Chenyu

2011-02-01

Full Text Available Abstract Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To meet the new challenges of controlling brain metastasis, the research community has been tackling the problem with novel experimental models and research tools, which have led to an improved understanding of brain metastasis. The time-tested "seed-and-soil" hypothesis of metastasis indicates that successful outgrowth of deadly metastatic tumors depends on permissible interactions between the metastatic cancer cells and the site-specific microenvironment in the host organs. Consistently, recent studies indicate that the brain, the major component of the central nervous system, has unique physiological features that can determine the outcome of metastatic tumor growth. The current review summarizes recent discoveries on these tumor-brain interactions, and the potential clinical implications these novel findings could have for the better treatment of patients with brain metastasis.

Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

Energy Technology Data Exchange (ETDEWEB)

Goffart, Nicolas [Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liège, Liège 4000 (Belgium); Kroonen, Jérôme [Human Genetics, CHU and University of Liège, Liège 4000 (Belgium); The T& P Bohnenn Laboratory for Neuro-Oncology, Department of Neurology and Neurosurgery, UMC Utrecht, Utrecht 3556 (Netherlands); Rogister, Bernard, E-mail: Bernard.Register@ulg.ac.be [Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liège, Liège 4000 (Belgium); Department of Neurology, CHU and University of Liège, Liège 4000 (Belgium); GIGA-Development, Stem Cells and Regenerative Medicine, University of Liège, Liège 4000 (Belgium)

2013-08-14

Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

International Nuclear Information System (INIS)

Goffart, Nicolas; Kroonen, Jérôme; Rogister, Bernard

2013-01-01

Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology

Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

Directory of Open Access Journals (Sweden)

Nicolas Goffart

2013-08-01

Full Text Available Glioblastoma multiforme (GBM, WHO grade IV is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

An Alternative Perspective for Malaysian Engineering Education: A Review from Year 2000-2012

Science.gov (United States)

Jayarajah, Kamaleswaran; Saat, Rohaida Mohd; Rauf, Rose Amnah Abdul

2013-01-01

The purpose of this study is to explore the research base of engineering education in the "Journal of Engineering Education" ("JEE") through an analysis review of articles for a 12-year period, from 2000 to 2012. The research base review focuses on identifying five characteristics of engineering education: (a) temporal…

Adipocytes and Macrophages Interplay in the Orchestration of Tumor Microenvironment: New Implications in Cancer Progression

Directory of Open Access Journals (Sweden)

Luís Henrique Corrêa

2017-09-01

Full Text Available Inflammation has been known as one of the main keys to the establishment and progression of cancers. Chronic low-grade inflammation is also a strategic condition that underlies the causes and development of metabolic syndrome and obesity. Moreover, obesity has been largely related to poor prognosis of tumors by modulating tumor microenvironment with secretion of several inflammatory mediators by tumor-associated adipocytes (TAAs, which can modulate and recruit tumor-associated macrophages. Thus, the understanding of cellular and molecular mechanisms that underlay and link inflammation, obesity, and cancer is crucial to identify potential targets that interfere with this important route. Knowledge about the exact role of each component of the tumor microenvironment is not yet fully understood, but the new insights in literature highlight the essential role of adipocytes and macrophages interplay as key factor to determine the fate of cancer progression. In this review article, we focus on the functions of adipocytes and macrophages orchestrating cellular and molecular mechanisms that lead to inflammatory modulation in tumor microenvironment, which will be crucial to cancer establishment. We also emphasized the mechanisms by which the tumor promotes itself by recruiting and polarizing macrophages, discussing the role of adipocytes in this process. In addition, we discuss here the newest possible anticancer therapeutic treatments aiming to retard the development of the tumor based on what is known about cancer, adipocyte, and macrophage polarization.

A Systematic Literature Review of US Engineering Ethics Interventions.

Science.gov (United States)

Hess, Justin L; Fore, Grant

2018-04-01

Promoting the ethical formation of engineering students through the cultivation of their discipline-specific knowledge, sensitivity, imagination, and reasoning skills has become a goal for many engineering education programs throughout the United States. However, there is neither a consensus throughout the engineering education community regarding which strategies are most effective towards which ends, nor which ends are most important. This study provides an overview of engineering ethics interventions within the U.S. through the systematic analysis of articles that featured ethical interventions in engineering, published in select peer-reviewed journals, and published between 2000 and 2015. As a core criterion, each journal article reviewed must have provided an overview of the course as well as how the authors evaluated course-learning goals. In sum, 26 articles were analyzed with a coding scheme that included 56 binary items. The results indicate that the most common methods for integrating ethics into engineering involved exposing students to codes/standards, utilizing case studies, and discussion activities. Nearly half of the articles had students engage with ethical heuristics or philosophical ethics. Following the presentation of the results, this study describes in detail four articles to highlight less common but intriguing pedagogical methods and evaluation techniques. The findings indicate that there is limited empirical work on ethics education within engineering across the United States. Furthermore, due to the large variation in goals, approaches, and evaluation methods described across interventions, this study does not detail "best" practices for integrating ethics into engineering. The science and engineering education community should continue exploring the relative merits of different approaches to ethics education in engineering.

Optimization of the tumor microenvironment and nanomedicine properties simultaneously to improve tumor therapy.

Science.gov (United States)

Zhang, Bo; Shi, Wei; Jiang, Ting; Wang, Lanting; Mei, Heng; Lu, Heng; Hu, Yu; Pang, Zhiqing

2016-09-20

Effective delivery of nanomedicines to tumor tissues depends on both the tumor microenvironment and nanomedicine properties. Accordingly, tumor microenvironment modification or advanced design of nanomedicine was emerging to improve nanomedicine delivery to tumors. However, few studies have emphasized the necessity to optimize the tumor microenvironment and nanomedicine properties simultaneously to improve tumor treatment. In the present study, imatinib mesylate (IMA) was used to normalize the tumor microenvironment including platelet-derived growth factor receptor-β expression inhibition, tumor vessel normalization, and tumor perfusion improvement as demonstrated by immunofluorescence staining. In addition, the effect of tumor microenvironment normalization on tumor delivery of nanomedicines with different sizes was carefully investigated. It was shown that IMA treatment significantly reduced the accumulation of nanoparticles (NPs) around 110 nm but enhanced the accumulation of micelles around 23 nm by in vivo fluorescence imaging experiment. Furthermore, IMA treatment limited the distribution of NPs inside tumors but increased that of micelles with a more homogeneous pattern. Finally, the anti-tumor efficacy study displayed that IMA pretreatment could significantly increase the therapeutic effects of paclitaxel-loaded micelles. All-together, a new strategy to improve nanomedicine delivery to tumor was provided by optimizing both nanomedicine size and the tumor microenvironment simultaneously, and it will have great potential in clinics for tumor treatment.

Bioprinting for Neural Tissue Engineering.

Science.gov (United States)

Knowlton, Stephanie; Anand, Shivesh; Shah, Twisha; Tasoglu, Savas

2018-01-01

Bioprinting is a method by which a cell-encapsulating bioink is patterned to create complex tissue architectures. Given the potential impact of this technology on neural research, we review the current state-of-the-art approaches for bioprinting neural tissues. While 2D neural cultures are ubiquitous for studying neural cells, 3D cultures can more accurately replicate the microenvironment of neural tissues. By bioprinting neuronal constructs, one can precisely control the microenvironment by specifically formulating the bioink for neural tissues, and by spatially patterning cell types and scaffold properties in three dimensions. We review a range of bioprinted neural tissue models and discuss how they can be used to observe how neurons behave, understand disease processes, develop new therapies and, ultimately, design replacement tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hyaluronan, Cancer-Associated Fibroblasts and the Tumor Microenvironment in Malignant Progression

Directory of Open Access Journals (Sweden)

James B. McCarthy

2018-05-01

Full Text Available This review summarizes the roles of CAFs in forming a “cancerized” fibrotic stroma favorable to tumor initiation and dissemination, in particular highlighting the functions of the extracellular matrix component hyaluronan (HA in these processes. The structural complexity of the tumor and its host microenvironment is now well appreciated to be an important contributing factor to malignant progression and resistance-to-therapy. There are multiple components of this complexity, which include an extensive remodeling of the extracellular matrix (ECM and associated biomechanical changes in tumor stroma. Tumor stroma is often fibrotic and rich in fibrillar type I collagen and hyaluronan (HA. Cancer-associated fibroblasts (CAFs are a major source of this fibrotic ECM. CAFs organize collagen fibrils and these biomechanical alterations provide highways for invading carcinoma cells either under the guidance of CAFs or following their epithelial to mesenchymal transition (EMT. The increased HA metabolism of a tumor microenvironment instructs carcinoma initiation and dissemination by performing multiple functions. The key effects of HA reviewed here are its role in activating CAFs in pre-malignant and malignant stroma, and facilitating invasion by promoting motility of both CAFs and tumor cells, thus facilitating their invasion. Circulating CAFs (cCAFs also form heterotypic clusters with circulating tumor cells (CTC, which are considered to be pre-cursors of metastatic colonies. cCAFs are likely required for extravasation of tumors cells and to form a metastatic niche suitable for new tumor colony growth. Therapeutic interventions designed to target both HA and CAFs in order to limit tumor spread and increase response to current therapies are discussed.

Macromolecularly crowded in vitro microenvironments accelerate the production of extracellular matrix-rich supramolecular assemblies.

Science.gov (United States)

Kumar, Pramod; Satyam, Abhigyan; Fan, Xingliang; Collin, Estelle; Rochev, Yury; Rodriguez, Brian J; Gorelov, Alexander; Dillon, Simon; Joshi, Lokesh; Raghunath, Michael; Pandit, Abhay; Zeugolis, Dimitrios I

2015-03-04

Therapeutic strategies based on the principles of tissue engineering by self-assembly put forward the notion that functional regeneration can be achieved by utilising the inherent capacity of cells to create highly sophisticated supramolecular assemblies. However, in dilute ex vivo microenvironments, prolonged culture time is required to develop an extracellular matrix-rich implantable device. Herein, we assessed the influence of macromolecular crowding, a biophysical phenomenon that regulates intra- and extra-cellular activities in multicellular organisms, in human corneal fibroblast culture. In the presence of macromolecules, abundant extracellular matrix deposition was evidenced as fast as 48 h in culture, even at low serum concentration. Temperature responsive copolymers allowed the detachment of dense and cohesive supramolecularly assembled living substitutes within 6 days in culture. Morphological, histological, gene and protein analysis assays demonstrated maintenance of tissue-specific function. Macromolecular crowding opens new avenues for a more rational design in engineering of clinically relevant tissue modules in vitro.

Using a holistic approach to assess the impact of engineered nanomaterials inducing toxicity in aquatic systems.

Science.gov (United States)

He, Xiaojia; Aker, Winfred G; Leszczynski, Jerzy; Hwang, Huey-Min

2014-03-01

In this report, we critically reviewed selected intrinsic physicochemical properties of engineered nanomaterials (ENMs) and their role in the interaction of the ENMs with the immediate surroundings in representative aquatic environments. The behavior of ENMs with respect to dynamic microenvironments at the nano-bio-eco interface level, and the resulting impact on their toxicity, fate, and exposure potential are elaborated. Based on this literature review, we conclude that a holistic approach is urgently needed to fulfill our knowledge gap regarding the safety of discharged ENMs. This comparative approach affords the capability to recognize and understand the potential hazards of ENMs and their toxicity mechanisms, and ultimately to establish a quantitative and reliable system to predict such outcomes. Copyright © 2014. Published by Elsevier B.V.

Mechanical Engineering Department. Technical review

Energy Technology Data Exchange (ETDEWEB)

Simecka, W.B.; Condouris, R.A.; Talaber, C. (eds.)

1980-01-01

The Mechanical Engineering Department Technical Review is published to (1) inform the readers of various technical activities within the Department, (2) promote exchange of ideas, and (3) give credit to the personnel who are achieving the results. The report is formatted into two parts: technical achievements and publication abstracts. The first is divided into eight sections, one for each Division in the Department providing the reader with the names of the personnel and the Division accomplishing the work.

Mechanical engineering department technical review

International Nuclear Information System (INIS)

Carr, R.B.; Denney, R.M.

1981-01-01

The Mechanical Engineering Department Technical Review is published to: (1) inform the readers of various technical activities within the department, (2) promote exchange of ideas, and (3) give credit to the personnel who are achieving the results. The report is formatted into two parts: technical acievements and publication abstracts. The first is divided into eight sections, one for each division in the department providing the reader with the names of the personnel and the division accomplishing the work

Mechanical Engineering Department. Technical review

International Nuclear Information System (INIS)

Simecka, W.B.; Condouris, R.A.; Talaber, C.

1980-01-01

The Mechanical Engineering Department Technical Review is published to (1) inform the readers of various technical activities within the Department, (2) promote exchange of ideas, and (3) give credit to the personnel who are achieving the results. The report is formatted into two parts: technical achievements and publication abstracts. The first is divided into eight sections, one for each Division in the Department providing the reader with the names of the personnel and the Division accomplishing the work

The Microenvironment in Gliomas: Phenotypic Expressions

Directory of Open Access Journals (Sweden)

Davide Schiffer

2015-12-01

Full Text Available The microenvironment of malignant gliomas is described according to its definition in the literature. Beside tumor cells, a series of stromal cells (microglia/macrophages, pericytes, fibroblasts, endothelial cells, normal and reactive astrocytes represents the cell component, whereas a complex network of molecular signaling represents the functional component. Its most evident expressions are perivascular and perinecrotic niches that are believed to be the site of tumor stem cells or progenitors in the tumor. Phenotypically, both niches are not easily recognizable; here, they are described together with a critical revision of their concept. As for perinecrotic niches, an alternative interpretation is given about their origin that regards the tumor stem cells as the residue of those that populated hyperproliferating areas in which necroses develop. This is based on the concept that the stem-like is a status and not a cell type, depending on the microenvironment that regulates a conversion of tumor non-stem cells and tumor stem cells through a cell reprogramming.

Biological stoichiometry in tumor micro-environments.

Directory of Open Access Journals (Sweden)

Irina Kareva

Full Text Available Tumors can be viewed as evolving ecological systems, in which heterogeneous populations of cancer cells compete with each other and somatic cells for space and nutrients within the ecosystem of the human body. According to the growth rate hypothesis (GRH, increased phosphorus availability in an ecosystem, such as the tumor micro-environment, may promote selection within the tumor for a more proliferative and thus potentially more malignant phenotype. The applicability of the GRH to tumor growth is evaluated using a mathematical model, which suggests that limiting phosphorus availability might promote intercellular competition within a tumor, and thereby delay disease progression. It is also shown that a tumor can respond differently to changes in its micro-environment depending on the initial distribution of clones within the tumor, regardless of its initial size. This suggests that composition of the tumor as a whole needs to be evaluated in order to maximize the efficacy of therapy.

Porcine spermatogonial stem cells self-renew effectively in a three dimensional culture microenvironment.

Science.gov (United States)

Park, Ji Eun; Park, Min Hee; Kim, Min Seong; Park, Yeo Reum; Yun, Jung Im; Cheong, Hee Tae; Kim, Minseok; Choi, Jung Hoon; Lee, Eunsong; Lee, Seung Tae

2017-12-01

Generally, self-renewal of spermatogonial stem cells (SSCs) is maintained in vivo in a three-dimensional (3D) microenvironment consisting of the seminiferous tubule basement membrane, indicating the importance of the 3D microenvironment for in vitro culture of SSCs. Here, we report a 3D culture microenvironment that effectively maintains porcine SSC self-renewal during culture. Porcine SSCs were cultured in an agarose-based 3D hydrogel and in 2D culture plates either with or without feeder cells. Subsequently, the effects of 3D culture on the maintenance of undifferentiated SSCs were identified by analyzing cell colony formation and morphology, AP activity, and transcriptional and translational regulation of self-renewal-related genes and the effects on proliferation by analyzing cell viability and single cell-derived colony number. The 3D culture microenvironment constructed using a 0.2% (w/v) agarose-based 3D hydrogel showed the strongest maintenance of porcine SSC self-renewal and induced significant improvements in proliferation compared with 2D culture microenvironments. These results demonstrate that self-renewal of porcine SSCs can be maintained more effectively in a 3D than in a 2D culture microenvironment. Moreover, this will play a significant role in developing novel culture systems for SSCs derived from diverse species in the future, which will contribute to SSC-related research. © 2017 International Federation for Cell Biology.

The multifaceted role of the microenvironment in liver metastasis

DEFF Research Database (Denmark)

Van den Eynden, Gert G; Majeed, Ali W; Illemann, Martin

2013-01-01

arriving in the liver via the bloodstream encounter the microenvironment of the hepatic sinusoid. The interactions of the tumor cells with hepatic sinusoidal and extrasinusoidal cells (endothelial, Kupffer, stellate, and inflammatory cells) determine their fate. The sinusoidal cells can have a dual role......The liver is host to many metastatic cancers, particularly colorectal cancer, for which the last 2 decades have seen major advances in diagnosis and treatment. The liver is a vital organ, and the extent of its involvement with metastatic disease is a major determinant of survival. Metastatic cells...... arrested and survived the initial onslaught, tumors can grow within the liver in 3 distinct patterns, reflecting differing host responses, mechanisms of vascularization, and proteolytic activity. This review aims to present current knowledge of the interactions between the host liver cells and the invading...

Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

Science.gov (United States)

2016-09-01

regulators of branching morphogenesis during mammary gland development 17,18, arguing that normal mammary epithelial cells cooperate with these innate ...CD45+CD11b+F4/80+ cells lacking lymphoid and granulocytic markers (Supplementary Fig.3B). viSNE plots 30 of myelo- monocytic cells (Fig.5A) showed that...cancer cells and how the microenvironment in these primary sites named P-TMEM (Primary Tumor Microenvironment of Metastases) contribute to early

Effects of mechanical loading on human mesenchymal stem cells for cartilage tissue engineering.

Science.gov (United States)

Choi, Jane Ru; Yong, Kar Wey; Choi, Jean Yu

2018-03-01

Today, articular cartilage damage is a major health problem, affecting people of all ages. The existing conventional articular cartilage repair techniques, such as autologous chondrocyte implantation (ACI), microfracture, and mosaicplasty, have many shortcomings which negatively affect their clinical outcomes. Therefore, it is essential to develop an alternative and efficient articular repair technique that can address those shortcomings. Cartilage tissue engineering, which aims to create a tissue-engineered cartilage derived from human mesenchymal stem cells (MSCs), shows great promise for improving articular cartilage defect therapy. However, the use of tissue-engineered cartilage for the clinical therapy of articular cartilage defect still remains challenging. Despite the importance of mechanical loading to create a functional cartilage has been well demonstrated, the specific type of mechanical loading and its optimal loading regime is still under investigation. This review summarizes the most recent advances in the effects of mechanical loading on human MSCs. First, the existing conventional articular repair techniques and their shortcomings are highlighted. The important parameters for the evaluation of the tissue-engineered cartilage, including chondrogenic and hypertrophic differentiation of human MSCs are briefly discussed. The influence of mechanical loading on human MSCs is subsequently reviewed and the possible mechanotransduction signaling is highlighted. The development of non-hypertrophic chondrogenesis in response to the changing mechanical microenvironment will aid in the establishment of a tissue-engineered cartilage for efficient articular cartilage repair. © 2017 Wiley Periodicals, Inc.

Targeting Autophagy in the Tumor Microenvironment: New Challenges and Opportunities for Regulating Tumor Immunity

Directory of Open Access Journals (Sweden)

Bassam Janji

2018-04-01

Full Text Available Cancer cells evolve in the tumor microenvironment, which is now well established as an integral part of the tumor and a determinant player in cancer cell adaptation and resistance to anti-cancer therapies. Despite the remarkable and fairly rapid progress over the past two decades regarding our understanding of the role of the tumor microenvironment in cancer development, its precise contribution to cancer resistance is still fragmented. This is mainly related to the complexity of the “tumor ecosystem” and the diversity of the stromal cell types that constitute the tumor microenvironment. Emerging data indicate that several factors, such as hypoxic stress, activate a plethora of resistance mechanisms, including autophagy, in tumor cells. Hypoxia-induced autophagy in the tumor microenvironment also activates several tumor escape mechanisms, which effectively counteract anti-tumor immune responses mediated by natural killer and cytotoxic T lymphocytes. Therefore, strategies aiming at targeting autophagy in cancer cells in combination with other therapeutic strategies have inspired significant interest to overcome immunological tolerance and promote tumor regression. However, a number of obstacles still hamper the application of autophagy inhibitors in clinics. First, the lack of selectivity of the current pharmacological inhibitors of autophagy makes difficult to draw a clear statement about its effective contribution in cancer. Second, autophagy has been also described as an important mechanism in tumor cells involved in presentation of antigens to T cells. Third, there is a circumstantial evidence that autophagy activation in some innate immune cells may support the maturation of these cells, and it is required for their anti-tumor activity. In this review, we will address these aspects and discuss our current knowledge on the benefits and the drawbacks of targeting autophagy in the context of anti-tumor immunity. We believe that it is

Diesel Engine Convert to Port Injection CNG Engine Using Gaseous Injector Nozzle Multi Holes Geometries Improvement: A Review

OpenAIRE

Semin; Abdul R. Ismail; Rosli A. Bakar

2009-01-01

The objective of this study was to review the previous research in the development of gaseous fuel injector for port injection CNG engine converted from diesel engine. Problem statement: The regular development of internal combustion engines change direction to answer the two most important problems determining the development trends of engines technology and in particular, their combustion systems. They were environmental protection against emission and noise, shortage of hydrocarbon fuels, ...

Engineering 3D Models of Tumors and Bone to Understand Tumor-Induced Bone Disease and Improve Treatments

Science.gov (United States)

Kwakwa, Kristin A.; Vanderburgh, Joseph P.; Guelcher, Scott A.

2018-01-01

Purpose of Review Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical. Recent Findings 3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment. This review will discuss 3D models including polyurethane, silk, and collagen scaffolds that have been developed to study tumor-induced bone disease. In addition, we discuss 3D printing techniques used to better replicate the structure of bone. Summary 3D models that better replicate the bone microenvironment will help researchers better understand the dynamic interactions between tumors and the bone microenvironment, ultimately leading to better models for testing therapeutics and predicting patient outcomes. PMID:28646444

In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles.

Science.gov (United States)

Ozcelikkale, Altug; Moon, Hye-Ran; Linnes, Michael; Han, Bumsoo

2017-09-01

Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine. Microfluidics offer significant advantages over traditional macroscale cell cultures by enabling recapitulation of tumor microenvironment through precise control of physiological cues such as hydrostatic pressure, shear stress, oxygen, and nutrient gradients. Microfluidic systems have recently started to be adapted for screening of drugs and NPs under physiologically relevant settings. So far the two primary application areas of microfluidics in this area have been high-throughput screening using traditional culture settings such as single cells or multicellular tumor spheroids, and mimicry of tumor microenvironment for study of cancer-related cell-cell and cell-matrix interactions. These microfluidic technologies are also useful in modeling specific steps in NP delivery to tumor and characterize NP transport properties and outcomes by systematic variation of physiological conditions. Ultimately, it will be possible to design drug-screening platforms uniquely tailored for individual patient physiology using microfluidics. These in vitro models can contribute to development of precision medicine by enabling rapid and patient-specific evaluation of cancer nanomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1460. doi: 10.1002/wnan.1460 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Environmental concentrations of engineered nanomaterials: Review of modeling and analytical studies

International Nuclear Information System (INIS)

Gottschalk, Fadri; Sun, TianYin; Nowack, Bernd

2013-01-01

Scientific consensus predicts that the worldwide use of engineered nanomaterials (ENM) leads to their release into the environment. We reviewed the available literature concerning environmental concentrations of six ENMs (TiO 2 , ZnO, Ag, fullerenes, CNT and CeO 2 ) in surface waters, wastewater treatment plant effluents, biosolids, sediments, soils and air. Presently, a dozen modeling studies provide environmental concentrations for ENM and a handful of analytical works can be used as basis for a preliminary validation. There are still major knowledge gaps (e.g. on ENM production, application and release) that affect the modeled values, but over all an agreement on the order of magnitude of the environmental concentrations can be reached. True validation of the modeled values is difficult because trace analytical methods that are specific for ENM detection and quantification are not available. The modeled and measured results are not always comparable due to the different forms and sizes of particles that these two approaches target. -- Highlights: •Modeled environmental concentrations of engineered nanomaterials are reviewed. •Measured environmental concentrations of engineered nanomaterials are reviewed. •Possible validation of modeled data by measurements is critically evaluated. •Different approaches in modeling and measurement methods complicate validation. -- Modeled and measured environmental concentrations of engineered nanomaterials are reviewed and critically discussed

Nutrient sensing via mTOR in T cells maintains a tolerogenic microenvironment

Directory of Open Access Journals (Sweden)

Duncan eHowie

2014-08-01

Full Text Available We have proposed that tolerance can be maintained by the induction, by Treg cells, of a tolerogenic microenvironment within tolerated tissues that inhibits effector cell activity but which supports the generation of further Treg cells by infectious tolerance. Two important components of this tolerogenic microenvironment depend on metabolism and nutrient sensing. The first is due to the up-regulation of multiple enzymes that consume essential amino acids (EAAs, which are sensed in naive T cells primarily via inhibition of the mTOR pathway, which in turn encourages their further differentiation into foxp3+ Treg cells. The second mechanism is the metabolism of extracellular ATP to adenosine by the ectoenzymes CD39 and CD73. These two enzymes are constitutively co-expressed on Treg cells, but can also be induced on a wide variety of cell types by TGFbeta and the adenosine generated can be shown to be a potent inhibitor of T cell proliferation. This review will focus on mechanisms of nutrient sensing in T cells, how these are integrated with TCR and cytokine signals via the mnTOR pathway, and what impact this has on intracellular metabolism and subsequently the control of differentiation into different effector or regulatory T cell subsets.

ERG [Engineering Review Group] review of the SRP [Salt Repository Project] salt irradiation effects program: Technical report

International Nuclear Information System (INIS)

Clark, D.E.

1986-11-01

The Engineering Review Group (ERG) was established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering-related issues in the US Department of Energy's nuclear waste repository program. The August 1985 meeting of the ERG reviewed the Salt Repository Project (SRP) salt irradiation effects program. This report documents the ERG's comments and recommendations on these subjects and the ONWI response to the specific points raised by the ERG

Probing the tumor microenvironment: collection and induction

Science.gov (United States)

Williams, James K.; Padgen, Michael R.; Wang, Yarong; Entenberg, David; Gertler, Frank; Condeelis, John S.; Castracane, James

2012-03-01

The Nano Intravital Device, or NANIVID, is under development as an optically transparent, implantable tool to study the tumor microenvironment. Two etched glass substrates are sealed using a thin polymer membrane to create a reservoir with a single outlet. This reservoir is loaded with a hydrogel blend that contains growth factors or other chemicals to be delivered to the tumor microenvironment. When the device is implanted in the tumor, the hydrogel will swell and release these entrapped molecules, forming a gradient. Validation of the device has been performed in vitro using epidermal growth factor (EGF) and MenaINV, a highly invasive, rat mammary adenocarcinoma cell line. In both 2-D and 3-D environments, cells migrated toward the gradient of EGF released from the device. The chorioallantoic membrane (CAM) of White Leghorn chicken eggs is being utilized to grow xenograft tumors that will be used for ex vivo cell collection. Device optimization is being performed for in vivo use as a tool to collect the invasive cell population. Preliminary cell collection experiments in vivo were performed using a mouse model of breast cancer. As a second application, the device is being explored as a delivery vehicle for chemicals that induce controlled changes in the tumor microenvironment. H2O2 was loaded in the device and generated intracellular reactive oxygen species (ROS) in cells near the device outlet. In the future, other induction targets will be explored, including hypoglycemia and the manipulation of extracellular matrix stiffness.

REQUIREMENT VERIFICATION AND SYSTEMS ENGINEERING TECHNICAL REVIEW (SETR) ON A COMMERCIAL DERIVATIVE AIRCRAFT (CDA) PROGRAM

Science.gov (United States)

2017-09-01

VERIFICATION AND SYSTEMS ENGINEERING TECHNICAL REVIEW (SETR) ON A COMMERCIAL DERIVATIVE AIRCRAFT (CDA) PROGRAM by Theresa L. Thomas September... ENGINEERING TECHNICAL REVIEW (SETR) ON A COMMERCIAL DERIVATIVE AIRCRAFT (CDA) PROGRAM 5. FUNDING NUMBERS 6. AUTHOR(S) Theresa L. Thomas 7...CODE 13. ABSTRACT (maximum 200 words) The Naval Air Systems Command (NAVAIR) systems engineering technical review (SETR) process does not

Remodeling the Vascular Microenvironment of Glioblastoma with α-Particles.

Science.gov (United States)

Behling, Katja; Maguire, William F; Di Gialleonardo, Valentina; Heeb, Lukas E M; Hassan, Iman F; Veach, Darren R; Keshari, Kayvan R; Gutin, Philip H; Scheinberg, David A; McDevitt, Michael R

2016-11-01

Tumors escape antiangiogenic therapy by activation of proangiogenic signaling pathways. Bevacizumab is approved for the treatment of recurrent glioblastoma, but patients inevitably develop resistance to this angiogenic inhibitor. We previously investigated targeted α-particle therapy with 225 Ac-E4G10 as an antivascular approach and showed increased survival and tumor control in a high-grade transgenic orthotopic glioblastoma model. Here, we investigated changes in tumor vascular morphology and functionality caused by 225 Ac-E4G10. We investigated remodeling of the tumor microenvironment in transgenic Ntva glioblastoma mice using a therapeutic 7.4-kBq dose of 225 Ac-E4G10. Immunofluorescence and immunohistochemical analyses imaged morphologic changes in the tumor blood-brain barrier microenvironment. Multicolor flow cytometry quantified the endothelial progenitor cell population in the bone marrow. Diffusion-weighted MR imaged functional changes in the tumor vascular network. The mechanism of drug action is a combination of remodeling of the glioblastoma vascular microenvironment, relief of edema, and depletion of regulatory T and endothelial progenitor cells. The primary remodeling event is the reduction of both endothelial and perivascular cell populations. Tumor-associated edema and necrosis were lessened, resulting in increased perfusion and reduced diffusion. Pharmacologic uptake of dasatinib into tumor was enhanced after α-particle therapy. Targeted antivascular α-particle radiation remodels the glioblastoma vascular microenvironment via a multimodal mechanism of action and provides insight into the vascular architecture of platelet-derived growth factor-driven glioblastoma. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

A study for radiation-related tumor microenvironment

International Nuclear Information System (INIS)

Son, Young Sook; Hong, Seok Il; Kim, Young Soon; Jin Yong Jae; Lee, Tae Hee; Chung, Eun Kyung; Yi, Jae Yeun; Park, Myung Jin; Kim, Yun Young; Kang, Sin Keun

1999-04-01

In this study, we attempted to elucidate the mechanism involved in radiation-induced modification and changes of biological factors and physicochemical factors of tumor microenvironment and develop techniques and agents for the modification of tumor microenvironment which is favorable for efficient radio-cancer therapy based on our basic study. We established in vitro tumor invasion and angiogenesis model, elucidated the importance of MMPs activation and the MMPs/TIMPs complex in the invasive transition of tumor. Furthermore we showed the signaling pathway for MMPs induction through EGF receptor and TGF beta 1 stimulated E-M transition. We also established primary culture of human endothelial cells and tubule forming condition which is utilized for the detection of novel angiogenic factors. We also identified hypoxia induced signaling pathway and showed that GBE improved blood perfusion which may increase the effectiveness of radio-cancer therapy

A study for radiation-related tumor microenvironment

Energy Technology Data Exchange (ETDEWEB)

Son, Young Sook; Hong, Seok Il; Kim, Young Soon; Jin Yong Jae; Lee, Tae Hee; Chung, Eun Kyung; Yi, Jae Yeun; Park, Myung Jin; Kim, Yun Young; Kang, Sin Keun

1999-04-01

In this study, we attempted to elucidate the mechanism involved in radiation-induced modification and changes of biological factors and physicochemical factors of tumor microenvironment and develop techniques and agents for the modification of tumor microenvironment which is favorable for efficient radio-cancer therapy based on our basic study. We established in vitro tumor invasion and angiogenesis model, elucidated the importance of MMPs activation and the MMPs/TIMPs complex in the invasive transition of tumor. Furthermore we showed the signaling pathway for MMPs induction through EGF receptor and TGF beta 1 stimulated E-M transition. We also established primary culture of human endothelial cells and tubule forming condition which is utilized for the detection of novel angiogenic factors. We also identified hypoxia induced signaling pathway and showed that GBE improved blood perfusion which may increase the effectiveness of radio-cancer therapy.

Cutaneous mast cell maturation does not depend on an intact bone marrow microenvironment

International Nuclear Information System (INIS)

Charley, M.R.; Mikhael, A.; Sontheimer, R.D.; Gilliam, J.N.; Bennett, M.

1984-01-01

A study was made to determine whether the maturation of murine cutaneous mast cells from stem cells depends on an intact bone marrow microenvironment. Normal bone marrow cells (+/+) were infused into 2 groups of mast cell-deficient mice: WBB6F1-W/Wv mice and 89 Sr-pretreated W/Wv mice. 89 Sr is a long-lived bone-seeking radioisotope which provides continuous irradiation of the marrow and thereby ablates the marrow microenvironment. Skin biopsies revealed that the 89 Sr-pretreated mice and the controls had repopulated their skin with mast cells equally well. Natural killer cell function was significantly depressed in the 89 Sr-treated mice, confirming that the marrow microenvironment had been functionally altered. It appears that, although the precursors for cutaneous mast cells are marrow derived, they do not need an intact marrow microenvironment for maturation

Bioprinting the Cancer Microenvironment.

Science.gov (United States)

Zhang, Yu Shrike; Duchamp, Margaux; Oklu, Rahmi; Ellisen, Leif W; Langer, Robert; Khademhosseini, Ali

2016-10-10

Cancer is intrinsically complex, comprising both heterogeneous cellular compositions and microenvironmental cues. During the various stages of cancer initiation, development, and metastasis, cell-cell interactions (involving vascular and immune cells besides cancerous cells) as well as cell-extracellular matrix (ECM) interactions (e.g., alteration in stiffness and composition of the surrounding matrix) play major roles. Conventional cancer models both two- and three-dimensional (2D and 3D) present numerous limitations as they lack good vascularization and cannot mimic the complexity of tumors, thereby restricting their use as biomimetic models for applications such as drug screening and fundamental cancer biology studies. Bioprinting as an emerging biofabrication platform enables the creation of high-resolution 3D structures and has been extensively used in the past decade to model multiple organs and diseases. More recently, this versatile technique has further found its application in studying cancer genesis, growth, metastasis, and drug responses through creation of accurate models that recreate the complexity of the cancer microenvironment. In this review we will focus first on cancer biology and limitations with current cancer models. We then detail the current bioprinting strategies including the selection of bioinks for capturing the properties of the tumor matrices, after which we discuss bioprinting of vascular structures that are critical toward construction of complex 3D cancer organoids. We finally conclude with current literature on bioprinted cancer models and propose future perspectives.

Review on film cooling of liquid rocket engines

Directory of Open Access Journals (Sweden)

S.R. Shine

2018-03-01

Full Text Available Film cooling in combination with regenerative cooling is presently considered as an efficient method to guarantee safe operation of liquid rocket engines having higher heat flux densities for long duration. This paper aims to bring all the research carried out in the field of liquid rocket engine film cooling since 1950. The analytical and numerical procedure followed, experimental facilities and measurements made and major inferences drawn are reviewed in detail, and compared where ever possible. Review has been made through a discussion of the analyses methodologies and the factors that influence film cooling performance. An effort has also been made to determine the status of the research, pointing out critical gaps, which are still to be explained and addressed by future generations. Keywords: Heat transfer, Liquid rocket thrust chamber, Film cooling, Cooling effectiveness

Contribution to Tumor Angiogenesis From Innate Immune Cells Within the Tumor Microenvironment: Implications for Immunotherapy

Directory of Open Access Journals (Sweden)

Adriana Albini

2018-04-01

Full Text Available The critical role of angiogenesis in promoting tumor growth and metastasis is strongly established. However, tumors show considerable variation in angiogenic characteristics and in their sensitivity to antiangiogenic therapy. Tumor angiogenesis involves not only cancer cells but also various tumor-associated leukocytes (TALs and stromal cells. TALs produce chemokines, cytokines, proteases, structural proteins, and microvescicles. Vascular endothelial growth factor (VEGF and inflammatory chemokines are not only major proangiogenic factors but are also immune modulators, which increase angiogenesis and lead to immune suppression. In our review, we discuss the regulation of angiogenesis by innate immune cells in the tumor microenvironment, specific features, and roles of major players: macrophages, neutrophils, myeloid-derived suppressor and dendritic cells, mast cells, γδT cells, innate lymphoid cells, and natural killer cells. Anti-VEGF or anti-inflammatory drugs could balance an immunosuppressive microenvironment to an immune permissive one. Anti-VEGF as well as anti-inflammatory drugs could therefore represent partners for combinations with immune checkpoint inhibitors, enhancing the effects of immune therapy.

Tumor Microenvironment Gene Signature as a Prognostic Classifier and Therapeutic Target

Science.gov (United States)

2016-06-01

AWARD NUMBER: W81XWH-14-1-0107 TITLE: Tumor Microenvironment Gene Signature as a Prognostic Classifier and Therapeutic Target PRINCIPAL...AND SUBTITLE Tumor Microenvironment Gene Signature as a 5a. CONTRACT NUMBER W81XWH-14-1-0107 Prognostic Classifier and Therapeutic Target 5b...gene signature that correlates with poor survival in ovarian cancer patients. We are refining this gene signature to develop biomarkers for the

Using Model-Based Systems Engineering To Provide Artifacts for NASA Project Life-Cycle and Technical Reviews

Science.gov (United States)

Parrott, Edith L.; Weiland, Karen J.

2017-01-01

The ability of systems engineers to use model-based systems engineering (MBSE) to generate self-consistent, up-to-date systems engineering products for project life-cycle and technical reviews is an important aspect for the continued and accelerated acceptance of MBSE. Currently, many review products are generated using labor-intensive, error-prone approaches based on documents, spreadsheets, and chart sets; a promised benefit of MBSE is that users will experience reductions in inconsistencies and errors. This work examines features of SysML that can be used to generate systems engineering products. Model elements, relationships, tables, and diagrams are identified for a large number of the typical systems engineering artifacts. A SysML system model can contain and generate most systems engineering products to a significant extent and this paper provides a guide on how to use MBSE to generate products for project life-cycle and technical reviews. The use of MBSE can reduce the schedule impact usually experienced for review preparation, as in many cases the review products can be auto-generated directly from the system model. These approaches are useful to systems engineers, project managers, review board members, and other key project stakeholders.

Innate lymphoid cells and their stromal microenvironments.

Science.gov (United States)

Kellermayer, Zoltán; Vojkovics, Dóra; Balogh, Péter

2017-09-01

In addition to the interaction between antigen presenting cells, T and B lymphocytes, recent studies have revealed important roles for a diverse set of auxiliary cells that profoundly influence the induction and regulation of immune responses against pathogens. Of these the stromal cells composed of various non-hematopoietic constituents are crucial for the creation and maintenance of specialized semi-static three-dimensional lymphoid tissue microenvironment, whereas the more recently described innate lymphoid cells are generated by the diversification of committed lymphoid precursor cells independently from clonally rearranged antigen receptor genes. Recent findings have revealed important contributions by innate lymphoid cells in inflammation and protection against pathogens in a tissue-specific manner. Importantly, lymphoid stromal cells also influence the onset of immune responses in tissue-specific fashion, raising the possibility of tissue-specific stromal - innate lymphoid cell collaboration. In this review we summarize the main features and interactions between these two cells types, with particular emphasis on ILC type 3 cells and their microenvironmental partners. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Chemical and physical microenvironments at the Viking landing sites

Science.gov (United States)

Clark, B. C.

1979-01-01

Physical and chemical considerations permit the division of the near-surface regolith on Mars into at least six zones of distinct microenvironments. The zones are euphotic, duricrust/peds, tempofrost, permafrost, endolithic, and interfacial/transitional. Microenvironments vary significantly in temperature extremes, mean temperature, salt content, relative pressure of water vapor, UV and visible light irradiance, and exposure to ionizing radiation events (100 Mrad) and oxidative molecular species. From what is known of the chemistry of the atmosphere and regolith fines (soil), limits upon the aqueous chemistry of soil pastes may be estimated. Heat of wetting could reach 45 cal/g dry soil; initial pH is indeterminate between 1 and 10; ionic strength and salinity are predicted to be extremely high; freezing point depression is inadequate to provide quantities of liquid water except in special cases. The prospects for biotic survival are grim by terrestrial standards, but the extremes of biological resiliency are inaccessible to evaluation. Second-generation in situ experiments which will better define Martian microenvironments are clearly possible. Antarctic dry valleys are approximations to Martian conditions, but deviate significantly by at least half-a-dozen criteria.

Double-Blind Review in Software Engineering Venues : The Community’s Perspective

NARCIS (Netherlands)

Bacchelli, A.; Beller, M.M.

2017-01-01

The peer review process is central to the scientific method, the advancement and spread of research, as well as crucial for individual careers. However, the single-blind review mode currently used in most Software Engineering (SE) venues is susceptible to apparent and hidden biases, since reviewers

Human factors engineering program review model

International Nuclear Information System (INIS)

1994-07-01

The staff of the Nuclear Regulatory Commission is performing nuclear power plant design certification reviews based on a design process plan that describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification and an acceptable implemented design. There are two principal reasons for this approach. First, the initial design certification applications submitted for staff review did not include detailed design information. Second, since human performance literature and industry experiences have shown that many significant human factors issues arise early in the design process, review of the design process activities and results is important to the evaluation of an overall design. However, current regulations and guidance documents do not address the criteria for design process review. Therefore, the HFE Program Review Model (HFE PRM) was developed as a basis for performing design certification reviews that include design process evaluations as well as review of the final design. A central tenet of the HFE PRM is that the HFE aspects of the plant should be developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The HFE PRM consists of ten component elements. Each element in divided into four sections: Background, Objective, Applicant Submittals, and Review Criteria. This report describes the development of the HFE PRM and gives a detailed description of each HFE review element

TOPICAL REVIEW: Progress in engineering high strain lead-free piezoelectric ceramics

Science.gov (United States)

Leontsev, Serhiy O.; Eitel, Richard E.

2010-08-01

Environmental concerns are strongly driving the need to replace the lead-based piezoelectric materials currently employed as multilayer actuators. The current review describes both compositional and structural engineering approaches to achieve enhanced piezoelectric properties in lead-free materials. The review of the compositional engineering approach focuses on compositional tuning of the properties and phase behavior in three promising families of lead-free perovskite ferroelectrics: the titanate, alkaline niobate and bismuth perovskites and their solid solutions. The 'structural engineering' approaches focus instead on optimization of microstructural features including grain size, grain orientation or texture, ferroelectric domain size and electrical bias field as potential paths to induce large piezoelectric properties in lead-free piezoceramics. It is suggested that a combination of both compositional and novel structural engineering approaches will be required in order to realize viable lead-free alternatives to current lead-based materials for piezoelectric actuator applications.

LPG diesel dual fuel engine – A critical review

Directory of Open Access Journals (Sweden)

B. Ashok

2015-06-01

Full Text Available The engine, which uses both conventional diesel fuel and LPG fuel, is referred to as ‘LPG–diesel dual fuel engines’. LPG dual fuel engines are modified diesel engines which use primary fuel as LPG and secondary fuel as diesel. LPG dual fuel engines have a good thermal efficiency at high output but the performance is less during part load conditions due to the poor utilization of charges. This problem can be overcome by varying factors such as pilot fuel quantity, injection timing, composition of the gaseous fuel and intake charge conditions, for improving the performance, combustion and emissions of dual fuel engines. This article reviews about the research work done by the researchers in order to improve the performance, combustion and emission parameters of a LPG–diesel dual fuel engines. From the studies it is shown that the use of LPG in diesel engine is one of the capable methods to reduce the PM and NOx emissions but at same time at part load condition there is a drop in efficiency and power output with respect to diesel operation.

Human-factors engineering-control-room design review: Shoreham Nuclear Power Station. Draft audit report

International Nuclear Information System (INIS)

Peterson, L.R.; Preston-Smith, J.; Savage, J.W.; Rousseau, W.F.

1981-01-01

A human factors engineering preliminary design review of the Shoreham control room was performed at the site on March 30 through April 3, 1981. This design review was carried out by a team from the Human Factors Engineering Branch, Division of Human Factors Safety. This report was prepared on the basis of the HFEB's review of the applicant's Preliminary Design Assessment and the human factors engineering design review/audit performed at the site. The presented sections are numbered to conform to the guidelines of the draft version of NUREG-0700. They summarize the teams's observations of the control room design and layout, and of the control room operators' interface with the control room environment

A method to fabricate solid free form scaffolds for liver tissue engineering by using 3D printing

OpenAIRE

Mallikarjunaiah, Chetan Aradhya

2015-01-01

In recent years, there has been a great demand for the development of bio-artificial organs/tissues in the field of organ transplantation and in-vitro toxicological drug screening (L. G. Griffith & Swartz, 2006). Engineering of functional tissue/organs by controlling the cells microenvironment to resemble in vivo situation is of central importance. This has led to the evolution of various techniques for controlling the cellular microenvironment to facilitate cell proliferation, organization a...

Women and Minorities in Engineering: A Review of the Literature

Science.gov (United States)

Mamaril, Natasha J. A; Royal, Kenneth D.

2008-01-01

This review of the literature investigates the various factors identified by researchers to explain women's underrepresentation in the engineering field. Because a great deal of research has been published through the years, a compilation summary of existing research was necessary. This literature review utilized searches from thousands of…

Global niche of marine anaerobic metabolisms expanded by particle microenvironments

Science.gov (United States)

Bianchi, Daniele; Weber, Thomas S.; Kiko, Rainer; Deutsch, Curtis

2018-04-01

In ocean waters, anaerobic microbial respiration should be confined to the anoxic waters found in coastal regions and tropical oxygen minimum zones, where it is energetically favourable. However, recent molecular and geochemical evidence has pointed to a much broader distribution of denitrifying and sulfate-reducing microbes. Anaerobic metabolisms are thought to thrive in microenvironments that develop inside sinking organic aggregates, but the global distribution and geochemical significance of these microenvironments is poorly understood. Here, we develop a new size-resolved particle model to predict anaerobic respiration from aggregate properties and seawater chemistry. Constrained by observations of the size spectrum of sinking particles, the model predicts that denitrification and sulfate reduction can be sustained throughout vast, hypoxic expanses of the ocean, and could explain the trace metal enrichment observed in particles due to sulfide precipitation. Globally, the expansion of the anaerobic niche due to particle microenvironments doubles the rate of water column denitrification compared with estimates based on anoxic zones alone, and changes the sensitivity of the marine nitrogen cycle to deoxygenation in a warming climate.

Role of the Microenvironment in Ovarian Cancer Stem Cell Maintenance

Directory of Open Access Journals (Sweden)

Jennifer Pasquier

2013-01-01

Full Text Available Despite recent progresses in cancer therapy and increased knowledge in cancer biology, ovarian cancer remains a challenging condition. Among the latest concepts developed in cancer biology, cancer stem cells and the role of microenvironment in tumor progression seem to be related. Indeed, cancer stem cells have been described in several solid tumors including ovarian cancers. These particular cells have the ability to self-renew and reconstitute a heterogeneous tumor. They are characterized by specific surface markers and display resistance to therapeutic regimens. During development, specific molecular cues from the tumor microenvironment can play a role in maintaining and expanding stemness of cancer cells. The tumor stroma contains several compartments: cellular component, cytokine network, and extracellular matrix. These different compartments interact to form a permissive niche for the cancer stem cells. Understanding the molecular cues underlying this crosstalk will allow the design of new therapeutic regimens targeting the niche. In this paper, we will discuss the mechanisms implicated in the interaction between ovarian cancer stem cells and their microenvironment.

[Improving industrial microbial stress resistance by metabolic engineering: a review].

Science.gov (United States)

Fu, Ruiyan; Li, Yin

2010-09-01

Metabolic engineering is a technologic platform for industrial strain improvement and aims not only at modifying microbial metabolic fluxes, but also improving the physiological performance of industrial microbes. Microbes will meet multiple stresses in industrial processes. Consequently, elicited gene responses might result in a decrease in overall cell fitness and the efficiency of biotransformation. Thus, it is crucial to develop robust and productive microbial strains that can be integrated into industrial-scale bioprocesses. In this review, we focus on the progress of these novel methods and strategies for engineering stress-tolerance phenotypes referring to rational metabolic engineering and inverse metabolic engineering in recent years. In addition, we also address problems existing in this area and future research needs of microbial physiological functionality engineering.

Direct laser writing by two-photon polymerization as a tool for developing microenvironments for evaluation of bacterial growth

Energy Technology Data Exchange (ETDEWEB)

Otuka, A.J.G. [Instituto de Física de São Carlos, Universidade de São Paulo, CP.369, 13560-970 São Carlos, SP (Brazil); Corrêa, D.S. [Laboratório Nacional de Nanotecnologia para o Agronegócio (LNNA), Embrapa Instrumentação, Rua XV de Novembro, 1452, CP.741, 13560-970 São Carlos, SP (Brazil); Fontana, C.R. [Department of Clinical Analysis, School of Pharmaceutical Sciences, University of São Paulo State (UNESP), 1621 Expedicionarios do Brasil Street, Araraquara, Sao Paulo 14801-960 (Brazil); Mendonça, C.R., E-mail: crmendon@ifsc.usp.br [Instituto de Física de São Carlos, Universidade de São Paulo, CP.369, 13560-970 São Carlos, SP (Brazil)

2014-02-01

Monitoring bacteria growth and motion in environments is fundamental to understand, for instance, how they proliferate and contaminate organism. Therefore, techniques to fabricate microenvironments for in situ and in vivo studies are interesting for that purpose. In this work we used two-photon polymerization to fabricate microenvironments and, as a proof of principle, we demonstrated the development of the bacteria ATCC 25922 Escherichia coli (E. coli) into the microstructure surroundings. Two varieties of polymeric microenvironments are presented: (i) a microenvironment doped at specific site with ciprofloxacin, an antibiotic typically used in the treatment of diseases caused by E. coli and (ii) micro-fences, which serve as traps for bacteria. These microenvironments, fabricated by two-photon polymerization, may be a potential platform for drug delivery system, by promoting or inhibiting the growth of bacteria in specific biological or synthetic sites. - Highlights: • Microenvironments were fabricated by two-photon polymerization. • We demonstrated the development of Escherichia coli into the microstructure surroundings. • Microenvironment doped with the antibiotic ciprofloxacin was fabricated. • Micro-fences, which serve as traps for bacteria, were also produced.

Direct laser writing by two-photon polymerization as a tool for developing microenvironments for evaluation of bacterial growth

International Nuclear Information System (INIS)

Otuka, A.J.G.; Corrêa, D.S.; Fontana, C.R.; Mendonça, C.R.

2014-01-01

Monitoring bacteria growth and motion in environments is fundamental to understand, for instance, how they proliferate and contaminate organism. Therefore, techniques to fabricate microenvironments for in situ and in vivo studies are interesting for that purpose. In this work we used two-photon polymerization to fabricate microenvironments and, as a proof of principle, we demonstrated the development of the bacteria ATCC 25922 Escherichia coli (E. coli) into the microstructure surroundings. Two varieties of polymeric microenvironments are presented: (i) a microenvironment doped at specific site with ciprofloxacin, an antibiotic typically used in the treatment of diseases caused by E. coli and (ii) micro-fences, which serve as traps for bacteria. These microenvironments, fabricated by two-photon polymerization, may be a potential platform for drug delivery system, by promoting or inhibiting the growth of bacteria in specific biological or synthetic sites. - Highlights: • Microenvironments were fabricated by two-photon polymerization. • We demonstrated the development of Escherichia coli into the microstructure surroundings. • Microenvironment doped with the antibiotic ciprofloxacin was fabricated. • Micro-fences, which serve as traps for bacteria, were also produced

Human-factors engineering control-room design review/audit: Waterford 3 SES Generating Station, Louisiana Power and Light Company

International Nuclear Information System (INIS)

Savage, J.W.

1983-01-01

A human factors engineering design review/audit of the Waterford-3 control room was performed at the site on May 10 through May 13, 1982. The report was prepared on the basis of the HFEB's review of the applicant's Preliminary Human Engineering Discrepancy (PHED) report and the human factors engineering design review performed at the site. This design review was carried out by a team from the Human Factors Engineering Branch, Division of Human Factors Safety. The review team was assisted by consultants from Lawrence Livermore National Laboratory (University of California), Livermore, California

Vascular and micro-environmental influences on MSC-coral hydroxyapatite construct-based bone tissue engineering.

Science.gov (United States)

Cai, Lei; Wang, Qian; Gu, Congmin; Wu, Jingguo; Wang, Jian; Kang, Ning; Hu, Jiewei; Xie, Fang; Yan, Li; Liu, Xia; Cao, Yilin; Xiao, Ran

2011-11-01

Bone tissue engineering (BTE) has been demonstrated an effective approach to generate bone tissue and repair bone defect in ectopic and orthotopic sites. The strategy of using a prevascularized tissue-engineered bone grafts (TEBG) fabricated ectopically to repair bone defects, which is called live bone graft surgery, has not been reported. And the quantitative advantages of vascularization and osteogenic environment in promoting engineered bone formation have not been defined yet. In the current study we generated a tissue engineered bone flap with a vascular pedicle of saphenous arteriovenous in which an organized vascular network was observed after 4 weeks implantation, and followed by a successful repaire of fibular defect in beagle dogs. Besides, after a 9 months long term observation of engineered bone formation in ectopic and orthotopic sites, four CHA (coral hydroxyapatite) scaffold groups were evaluated by CT (computed tomography) analysis. By the comparison of bone formation and scaffold degradation between different groups, the influences of vascularization and micro-environment on tissue engineered bone were quantitatively analyzed. The results showed that in the first 3 months vascularization improved engineered bone formation by 2 times of non-vascular group and bone defect micro-environment improved it by 3 times of ectopic group, and the CHA-scaffold degradation was accelerated as well. Copyright © 2011 Elsevier Ltd. All rights reserved.

77 FR 18268 - Proposal Review Panel for Engineering Education and Centers; Notice of Meeting

Science.gov (United States)

2012-03-27

... NATIONAL SCIENCE FOUNDATION Proposal Review Panel for Engineering Education and Centers; Notice of... Science Foundation announces the following meeting: Name: Proposal Review Panel for Engineering Education...--ERC Research Program 3:30 p.m.--7:30 p.m. Closed--ERC Education Program Thursday, March 29, 2012 8 a.m...

Changes in Cytokines of the Bone Microenvironment during Breast Cancer Metastasis

International Nuclear Information System (INIS)

Sosnoski, D.M.; Krishnan, V.; Mastro, A.M.; Kraemer, W.J.; Dunn-Lewis, C.

2012-01-01

It is commonly accepted that cancer cells interact with host cells to create a microenvironment favoring malignant colonization. The complex bone microenvironment produces an ever changing array of cytokines and growth factors. In this study, we examined levels of MCP-1, IL-6, KC, MIP-2, VEGF, MIG, and eotaxin in femurs of athymic nude mice inoculated via intracardiac injection with MDA-MB-231GFP human metastatic breast cancer cells, MDA-MB-231 BRMS1GFP, a metastasis suppressed variant, or PBS. Animals were euthanized (day 3, 11, 19, 27 after injection) to examine femoral cytokine levels at various stages of cancer cell colonization. The epiphysis contained significantly more cytokines than the diaphysis except for MIG which was similar throughout the bone. Variation among femurs was evident within all groups. By day 27, MCP-1, MIG, VEGF and eotaxin levels were significantly greater in femurs of cancer cell-inoculated mice. These pro-osteoclastic and angiogenic cytokines may manipulate the bone microenvironment to enhance cancer cell colonization

A review on the engine performance and exhaust emission characteristics of diesel engines fueled with biodiesel blends.

Science.gov (United States)

Damanik, Natalina; Ong, Hwai Chyuan; Tong, Chong Wen; Mahlia, Teuku Meurah Indra; Silitonga, Arridina Susan

2018-06-01

Biodiesels have gained much popularity because they are cleaner alternative fuels and they can be used directly in diesel engines without modifications. In this paper, a brief review of the key studies pertaining to the engine performance and exhaust emission characteristics of diesel engines fueled with biodiesel blends, exhaust aftertreatment systems, and low-temperature combustion technology is presented. In general, most biodiesel blends result in a significant decrease in carbon monoxide and total unburned hydrocarbon emissions. There is also a decrease in carbon monoxide, nitrogen oxide, and total unburned hydrocarbon emissions while the engine performance increases for diesel engines fueled with biodiesels blended with nano-additives. The development of automotive technologies, such as exhaust gas recirculation systems and low-temperature combustion technology, also improves the thermal efficiency of diesel engines and reduces nitrogen oxide and particulate matter emissions.

Human-factors engineering control-room design review/audit report: Byron Generating Station, Commonwealth Edison Company

International Nuclear Information System (INIS)

Savage, J.W.

1983-01-01

A human factors engineering design review/audit of the Byron Unit 1 control room was performed at the site on November 17 through November 19, 1981. This review was accomplished using the Unit 2 control room appropriately mocked-up to reflect design changes already committed to be incorporated in Unit 1. The report was prepared on the basis of the HFEB's audit of the applicant's Preliminary Design Assessment report and the human factors engineering design review performed at the site. This design review was carried out by a team from the Human Factors Engineering Branch, Division of Human Factors Safety. The review team was assisted by consultants from BioTechnology, Inc. (Falls Church, Virginia), and from Lawrence Livermore National Laboratory (University of California), Livermore, California

Near-Infrared Light-Sensitive Polyvinyl Alcohol Hydrogel Photoresist for Spatiotemporal Control of Cell-Instructive 3D Microenvironments.

Science.gov (United States)

Qin, Xiao-Hua; Wang, Xiaopu; Rottmar, Markus; Nelson, Bradley J; Maniura-Weber, Katharina

2018-03-01

Advanced hydrogel systems that allow precise control of cells and their 3D microenvironments are needed in tissue engineering, disease modeling, and drug screening. Multiphoton lithography (MPL) allows true 3D microfabrication of complex objects, but its biological application requires a cell-compatible hydrogel resist that is sufficiently photosensitive, cell-degradable, and permissive to support 3D cell growth. Here, an extremely photosensitive cell-responsive hydrogel composed of peptide-crosslinked polyvinyl alcohol (PVA) is designed to expand the biological applications of MPL. PVA hydrogels are formed rapidly by ultraviolet light within 1 min in the presence of cells, providing fully synthetic matrices that are instructive for cell-matrix remodeling, multicellular morphogenesis, and protease-mediated cell invasion. By focusing a multiphoton laser into a cell-laden PVA hydrogel, cell-instructive extracellular cues are site-specifically attached to the PVA matrix. Cell invasion is thus precisely guided in 3D with micrometer-scale spatial resolution. This robust hydrogel enables, for the first time, ultrafast MPL of cell-responsive synthetic matrices at writing speeds up to 50 mm s -1 . This approach should enable facile photochemical construction and manipulation of 3D cellular microenvironments with unprecedented flexibility and precision. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recent advances in hydrogels for cartilage tissue engineering

Directory of Open Access Journals (Sweden)

SL Vega

2017-01-01

Full Text Available Articular cartilage is a load-bearing tissue that lines the surface of bones in diarthrodial joints. Unfortunately, this avascular tissue has a limited capacity for intrinsic repair. Treatment options for articular cartilage defects include microfracture and arthroplasty; however, these strategies fail to generate tissue that adequately restores damaged cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. To date, a wide range of scaffolds and cell sources have emerged with a focus on recapitulating the microenvironments present during development or in adult tissue, in order to induce the formation of cartilaginous constructs with biochemical and mechanical properties of native tissue. Hydrogels have emerged as a promising scaffold due to the wide range of possible properties and the ability to entrap cells within the material. Towards improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Some of these advances include the development of improved network crosslinking (e.g. double-networks, new techniques to process hydrogels (e.g. 3D printing and better incorporation of biological signals (e.g. controlled release. This review summarises these innovative approaches to engineer hydrogels towards cartilage repair, with an eye towards eventual clinical translation.

Recent advances in hydrogels for cartilage tissue engineering.

Science.gov (United States)

Vega, S L; Kwon, M Y; Burdick, J A

2017-01-30

Articular cartilage is a load-bearing tissue that lines the surface of bones in diarthrodial joints. Unfortunately, this avascular tissue has a limited capacity for intrinsic repair. Treatment options for articular cartilage defects include microfracture and arthroplasty; however, these strategies fail to generate tissue that adequately restores damaged cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. To date, a wide range of scaffolds and cell sources have emerged with a focus on recapitulating the microenvironments present during development or in adult tissue, in order to induce the formation of cartilaginous constructs with biochemical and mechanical properties of native tissue. Hydrogels have emerged as a promising scaffold due to the wide range of possible properties and the ability to entrap cells within the material. Towards improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Some of these advances include the development of improved network crosslinking (e.g. double-networks), new techniques to process hydrogels (e.g. 3D printing) and better incorporation of biological signals (e.g. controlled release). This review summarises these innovative approaches to engineer hydrogels towards cartilage repair, with an eye towards eventual clinical translation.

Safety review for human factors engineering and control rooms of nuclear power plants

International Nuclear Information System (INIS)

Yang Mengzhuo

1998-01-01

Safety review for human factors engineering and control rooms of nuclear power plants (NPP) is in a forward position of science and technology, which began at American TMI severe accident and had been implemented in China. The importance and the significance of the safety review are expounded, the requirements of its scope and profundity are explained in detail. In addition, the situation of the technical document system for nuclear safety regulation on human factors engineering and control rooms of NPP in China is introduced briefly, on which the safety review is based

Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-Resistant Prostate Cancer

Science.gov (United States)

2017-12-01

AWARD NUMBER: W81XWH-13-1-0163 TITLE: Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-resistant Prostate Cancer ...Prostate Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Feng Yang, Ph.D. 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: fyang@bcm.edu...W81XWH-13-1-0163 " Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-resistant Prostate Cancer " Introduction AR signaling

Impaired regeneration: A role for the muscle microenvironment in cancer cachexia.

Science.gov (United States)

Talbert, Erin E; Guttridge, Denis C

2016-06-01

While changes in muscle protein synthesis and degradation have long been known to contribute to muscle wasting, a body of literature has arisen which suggests that regulation of the satellite cell and its ensuing regenerative program are impaired in atrophied muscle. Lessons learned from cancer cachexia suggest that this regulation is simply not a consequence, but a contributing factor to the wasting process. In addition to satellite cells, evidence from mouse models of cancer cachexia also suggests that non-satellite progenitor cells from the muscle microenvironment are also involved. This chapter in the series reviews the evidence of dysfunctional muscle repair in multiple wasting conditions. Potential mechanisms for this dysfunctional regeneration are discussed, particularly in the context of cancer cachexia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design considerations and challenges for mechanical stretch bioreactors in tissue engineering.

Science.gov (United States)

Lei, Ying; Ferdous, Zannatul

2016-05-01

With the increase in average life expectancy and growing aging population, lack of functional grafts for replacement surgeries has become a severe problem. Engineered tissues are a promising alternative to this problem because they can mimic the physiological function of the native tissues and be cultured on demand. Cyclic stretch is important for developing many engineered tissues such as hearts, heart valves, muscles, and bones. Thus a variety of stretch bioreactors and corresponding scaffolds have been designed and tested to study the underlying mechanism of tissue formation and to optimize the mechanical conditions applied to the engineered tissues. In this review, we look at various designs of stretch bioreactors and common scaffolds and offer insights for future improvements in tissue engineering applications. First, we summarize the requirements and common configuration of stretch bioreactors. Next, we present the features of different actuating and motion transforming systems and their applications. Since most bioreactors must measure detailed distributions of loads and deformations on engineered tissues, techniques with high accuracy, precision, and frequency have been developed. We also cover the key points in designing culture chambers, nutrition exchanging systems, and regimens used for specific tissues. Since scaffolds are essential for providing biophysical microenvironments for residing cells, we discuss materials and technologies used in fabricating scaffolds to mimic anisotropic native tissues, including decellularized tissues, hydrogels, biocompatible polymers, electrospinning, and 3D bioprinting techniques. Finally, we present the potential future directions for improving stretch bioreactors and scaffolds. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:543-553, 2016. © 2016 American Institute of Chemical Engineers.

Engineering stem cell niches in bioreactors

OpenAIRE

Liu, Meimei; Liu, Ning; Zang, Ru; Li, Yan; Yang, Shang-Tian

2013-01-01

Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as “ni...

Tissue engineering of urethra: Systematic review of recent literature.

Science.gov (United States)

Žiaran, Stanislav; Galambošová, Martina; Danišovič, L'uboš

2017-12-01

The purpose of this article was to perform a systematic review of the recent literature on urethral tissue engineering. A total of 31 articles describing the use of tissue engineering for urethra reconstruction were included. The obtained results were discussed in three groups: cells, scaffolds, and clinical results of urethral reconstructions using these components. Stem cells of different origin were used in many experimental studies, but only autologous urothelial cells, fibroblasts, and keratinocytes were applied in clinical trials. Natural and synthetic scaffolds were studied in the context of urethral tissue engineering. The main advantage of synthetic ones is the fact that they can be obtained in unlimited amount and modified by different techniques, but scaffolds of natural origin normally contain chemical groups and bioactive proteins which increase the cell attachment and may promote the cell proliferation and differentiation. The most promising are smart scaffolds delivering different bioactive molecules or those that can be tubularized. In two clinical trials, only onlay-fashioned transplants were used for urethral reconstruction. However, the very promising results were obtained from animal studies where tubularized scaffolds, both non-seeded and cell-seeded, were applied. Impact statement The main goal of this article was to perform a systematic review of the recent literature on urethral tissue engineering. It summarizes the most recent information about cells, seeded or non-seeded scaffolds and clinical application with respect to regeneration of urethra.

Prospects of pyrolysis oil from plastic waste as fuel for diesel engines: A review

Science.gov (United States)

Mangesh, V. L.; Padmanabhan, S.; Ganesan, S.; PrabhudevRahul, D.; Reddy, T. Dinesh Kumar

2017-05-01

The purpose ofthis study is to review the existing literature about chemical recycling of plastic waste and its potential as fuel for diesel engines. This is a review covering on the field of converting waste plastics into liquid hydrocarbon fuels for diesel engines. Disposal and recycling of waste plastics have become an incremental problem and environmental threat with increasing demand for plastics. One of the effective measures is by converting waste plastic into combustible hydrocarbon liquid as an alternative fuel for running diesel engines. Continued research efforts have been taken by researchers to convert waste plastic in to combustible pyrolysis oil as alternate fuel for diesel engines. An existing literature focuses on the study of chemical structure of the waste plastic pyrolysis compared with diesel oil. Converting waste plastics into fuel oil by different catalysts in catalytic pyrolysis process also reviewed in this paper. The methodology with subsequent hydro treating and hydrocracking of waste plastic pyrolysis oil can reduce unsaturated hydrocarbon bonds which would improve the combustion performance in diesel engines as an alternate fuel.

Extracellular Vesicles As Modulators of Tumor Microenvironment and Disease Progression in Glioma

Directory of Open Access Journals (Sweden)

Abir Mondal

2017-07-01

Full Text Available Diffuse gliomas are lethal tumors of the central nervous system (CNS characterized by infiltrative growth, aggressive nature, and therapeutic resistance. The recent 2016 WHO classification for CNS tumors categorizes diffuse glioma into two major types that include IDH wild-type glioblastoma, which is the predominant type and IDH-mutant glioblastoma, which is less common and displays better prognosis. Recent studies suggest presence of a distinct cell population with stem cell features termed as glioma stem cells (GSCs to be causal in driving tumor growth in glioblastoma. The presence of a stem and progenitor population possibly makes glioblastoma highly heterogeneous. Significantly, tumor growth is driven by interaction of cells residing within the tumor with the surrounding milieu termed as the tumor microenvironment. It comprises of various cell types such as endothelial cells, secreted factors, and the surrounding extracellular matrix, which altogether help perpetuate the proliferation of GSCs. One of the important mediators critical to the cross talk is extracellular vesicles (EVs. These nano-sized vesicles play important roles in intercellular communication by transporting bioactive molecules into the surrounding milieu, thereby altering cellular functions and/or reprogramming recipient cells. With the growing information on the contribution of EVs in modulation of the tumor microenvironment, it is important to determine their role in both supporting as well as promoting tumor growth in glioma. In this review, we provide a comprehensive overview of the role of EVs in tumor progression and glioma pathogenesis.

Adhesion of mesenchymal stem cells to biomimetic polymers: A review

Energy Technology Data Exchange (ETDEWEB)

Shotorbani, Behnaz Banimohamad [Research Institute for Fundamental Sciences (RIFS), University of Tabriz, Tabriz (Iran, Islamic Republic of); Alizadeh, Effat, E-mail: Alizadehe@tbzmed.ac.ir [Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz (Iran, Islamic Republic of); Drug Applied Research Center and Faculty of advanced Medical Science, Tabriz University of Medical Sciences, Tabriz (Iran, Islamic Republic of); The Umbilical Cord Stem Cell Research Center (UCSRC), Tabriz University of Medical Sciences, Tabriz (Iran, Islamic Republic of); Salehi, Roya [Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz (Iran, Islamic Republic of); Drug Applied Research Center and Faculty of advanced Medical Science, Tabriz University of Medical Sciences, Tabriz (Iran, Islamic Republic of); The Umbilical Cord Stem Cell Research Center (UCSRC), Tabriz University of Medical Sciences, Tabriz (Iran, Islamic Republic of); Barzegar, Abolfazl [Research Institute for Fundamental Sciences (RIFS), University of Tabriz, Tabriz (Iran, Islamic Republic of); Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz (Iran, Islamic Republic of)

2017-02-01

The mesenchymal stem cells (MSCs) are promising candidates for cell therapy due to the self-renewal, multi-potency, ethically approved state and suitability for autologous transplantation. However, key issue for isolation and manipulation of MSCs is adhesion in ex-vivo culture systems. Biomaterials engineered for mimicking natural extracellular matrix (ECM) conditions which support stem cell adhesion, proliferation and differentiation represent a main area of research in tissue engineering. Some of them successfully enhanced cells adhesion and proliferation because of their biocompatibility, biomimetic texture, and chemistry. However, it is still in its infancy, therefore intensification and optimization of in vitro, in vivo, and preclinical studies is needed to clarify efficacies as well as applicability of those bioengineered constructs. The aim of this review is to discuss mechanisms related to the in-vitro adhesion of MSCs, surfaces biochemical, biophysical, and other factors (of cell's natural and artificial micro-environment) which could affect it and a review of previous research attempting for its bio-chemo-optimization. - Highlights: • The main materials utilized for fabrication of biomimetic polymers are presented. • MSCs cell-material adhesion mechanism and involved molecules are reviewed. • Surface modifications of polymers in terms of MSC adhesion improving are discussed.

Adhesion of mesenchymal stem cells to biomimetic polymers: A review

International Nuclear Information System (INIS)

Shotorbani, Behnaz Banimohamad; Alizadeh, Effat; Salehi, Roya; Barzegar, Abolfazl

2017-01-01

The mesenchymal stem cells (MSCs) are promising candidates for cell therapy due to the self-renewal, multi-potency, ethically approved state and suitability for autologous transplantation. However, key issue for isolation and manipulation of MSCs is adhesion in ex-vivo culture systems. Biomaterials engineered for mimicking natural extracellular matrix (ECM) conditions which support stem cell adhesion, proliferation and differentiation represent a main area of research in tissue engineering. Some of them successfully enhanced cells adhesion and proliferation because of their biocompatibility, biomimetic texture, and chemistry. However, it is still in its infancy, therefore intensification and optimization of in vitro, in vivo, and preclinical studies is needed to clarify efficacies as well as applicability of those bioengineered constructs. The aim of this review is to discuss mechanisms related to the in-vitro adhesion of MSCs, surfaces biochemical, biophysical, and other factors (of cell's natural and artificial micro-environment) which could affect it and a review of previous research attempting for its bio-chemo-optimization. - Highlights: • The main materials utilized for fabrication of biomimetic polymers are presented. • MSCs cell-material adhesion mechanism and involved molecules are reviewed. • Surface modifications of polymers in terms of MSC adhesion improving are discussed.

Review of organic Rankine cycles for internal combustion engine exhaust waste heat recovery

International Nuclear Information System (INIS)

Sprouse, Charles; Depcik, Christopher

2013-01-01

Escalating fuel prices and future carbon dioxide emission limits are creating a renewed interest in methods to increase the thermal efficiency of engines beyond the limit of in-cylinder techniques. One promising mechanism that accomplishes both objectives is the conversion of engine waste heat to a more useful form of energy, either mechanical or electrical. This paper reviews the history of internal combustion engine exhaust waste heat recovery focusing on Organic Rankine Cycles since this thermodynamic cycle works well with the medium-grade energy of the exhaust. Selection of the cycle expander and working fluid are the primary focus of the review, since they are regarded as having the largest impact on system performance. Results demonstrate a potential fuel economy improvement around 10% with modern refrigerants and advancements in expander technology. -- Highlights: ► This review article focuses on engine exhaust waste heat recovery works. ► The organic Rankine cycle is superior for low to medium exergy heat sources. ► Working fluid and expander selection strongly influence efficiency. ► Several authors demonstrate viable systems for vehicle installation

Changes in Cytokines of the Bone Microenvironment during Breast Cancer Metastasis

Directory of Open Access Journals (Sweden)

Donna M. Sosnoski

2012-01-01

Full Text Available It is commonly accepted that cancer cells interact with host cells to create a microenvironment favoring malignant colonization. The complex bone microenvironment produces an ever changing array of cytokines and growth factors. In this study, we examined levels of MCP-1, IL-6, KC, MIP-2, VEGF, MIG, and eotaxin in femurs of athymic nude mice inoculated via intracardiac injection with MDA-MB-231GFP human metastatic breast cancer cells, MDA-MB-231BRMS1GFP, a metastasis suppressed variant, or PBS. Animals were euthanized (day 3, 11, 19, 27 after injection to examine femoral cytokine levels at various stages of cancer cell colonization. The epiphysis contained significantly more cytokines than the diaphysis except for MIG which was similar throughout the bone. Variation among femurs was evident within all groups. By day 27, MCP-1, MIG, VEGF and eotaxin levels were significantly greater in femurs of cancer cell-inoculated mice. These pro-osteoclastic and angiogenic cytokines may manipulate the bone microenvironment to enhance cancer cell colonization.

Biomimetic Materials and Fabrication Approaches for Bone Tissue Engineering.

Science.gov (United States)

Kim, Hwan D; Amirthalingam, Sivashanmugam; Kim, Seunghyun L; Lee, Seunghun S; Rangasamy, Jayakumar; Hwang, Nathaniel S

2017-12-01

Various strategies have been explored to overcome critically sized bone defects via bone tissue engineering approaches that incorporate biomimetic scaffolds. Biomimetic scaffolds may provide a novel platform for phenotypically stable tissue formation and stem cell differentiation. In recent years, osteoinductive and inorganic biomimetic scaffold materials have been optimized to offer an osteo-friendly microenvironment for the osteogenic commitment of stem cells. Furthermore, scaffold structures with a microarchitecture design similar to native bone tissue are necessary for successful bone tissue regeneration. For this reason, various methods for fabricating 3D porous structures have been developed. Innovative techniques, such as 3D printing methods, are currently being utilized for optimal host stem cell infiltration, vascularization, nutrient transfer, and stem cell differentiation. In this progress report, biomimetic materials and fabrication approaches that are currently being utilized for biomimetic scaffold design are reviewed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

76 FR 55389 - Federal Acquisition Regulation; Submission for OMB Review; Architect-Engineer Qualifications (SF...

Science.gov (United States)

2011-09-07

...; Submission for OMB Review; Architect-Engineer Qualifications (SF 330) AGENCIES: Department of Defense (DOD... extension of a previously approved information collection requirement for the Architect-Engineer... 330, Part I is used by all Executive agencies to obtain information from architect-engineer firms...

Breast cancer by proxy: Can the microenvironment be both the cause and consequence?

Energy Technology Data Exchange (ETDEWEB)

Ronnov-Jessen, Lone; Bissell, Mina J

2008-11-16

Breast cancer is one of the most clear-cut examples of a solid tumor in which systemic cues play a decisive part in its development. The breast tissue is constantly subjected to changes in hormone levels and modifications in the microenvironment. This scenario is even more striking during tumor development because of the dramatic loss or aberration of basement membrane (BM) and myoepithelial cells and the gain of peritumoral myofibroblasts. We suggest that the microenvironment, defined here as all components of the mammary gland other than luminal and/or tumor epithelial cells, might be instrumental in maintaining organ integrity and in promoting, and at times even initiating, breast cancer development. As such, the tumor microenvironment and its constituents, alone or in combination, might serve as promising targets for therapy.

Targets in the microenvironment of rectal cancer : A focus on angiogenic growth factors and chemokines

NARCIS (Netherlands)

Tamas, Karin Rita

2015-01-01

Cancer cells interact with each other, and with cells of the tumor microenvironment. This coincides with the production of numerous soluble factors which can stimulate cancer cell growth and migration. In addition the tumor microenvironment can facilitate cancer cells to escape the effect of

Applying Peer Reviews in Software Engineering Education: An Experiment and Lessons Learned

Science.gov (United States)

Garousi, V.

2010-01-01

Based on the demonstrated value of peer reviews in the engineering industry, numerous industry experts have listed it at the top of the list of desirable development practices. Experience has shown that problems (defects) are eliminated earlier if a development process incorporates peer reviews and that these reviews are as effective as or even…

Designing the stem cell microenvironment for guided connective tissue regeneration.

Science.gov (United States)

Bogdanowicz, Danielle R; Lu, Helen H

2017-12-01

Adult mesenchymal stem cells (MSCs) are an attractive cell source for regenerative medicine because of their ability to self-renew and their capacity for multilineage differentiation and tissue regeneration. For connective tissues, such as ligaments or tendons, MSCs are vital to the modulation of the inflammatory response following acute injury while also interacting with resident fibroblasts to promote cell proliferation and matrix synthesis. To date, MSC injection for connective tissue repair has yielded mixed results in vivo, likely due to a lack of appropriate environmental cues to effectively control MSC response and promote tissue healing instead of scar formation. In healthy tissues, stem cells reside within a complex microenvironment comprising cellular, structural, and signaling cues that collectively maintain stemness and modulate tissue homeostasis. Changes to the microenvironment following injury regulate stem cell differentiation, trophic signaling, and tissue healing. Here, we focus on models of the stem cell microenvironment that are used to elucidate the mechanisms of stem cell regulation and inspire functional approaches to tissue regeneration. Recent studies in this frontier area are highlighted, focusing on how microenvironmental cues modulate MSC response following connective tissue injury and, more importantly, how this unique cell environment can be programmed for stem cell-guided tissue regeneration. © 2017 New York Academy of Sciences.

Research on the NPP human factors engineering operating experience review

International Nuclear Information System (INIS)

Ren Xiangchen; Miao Hongxing; Ning Zhonghe

2006-01-01

This paper addresses the importance of the human factors engineering (HFE) for the design of nuclear power plant (NPP), especially for the design of human-machine interface in the NPP. It also summarizes the scope and content of the NPP HFE. The function, scope, content and process of the NPP human factors engineering operating experience review (OER) are mainly focused on, and significantly discussed. Finally, it briefly introduces the situation of the studies on the OER in China. (authors)

Effects of ground insulation and greenhouse microenvironment on ...

African Journals Online (AJOL)

A study was conducted at Egerton University, Njoro, Kenya to establish the potential of plastic digester to produce biogas under natural and greenhouse microenvironment. The specific objectives were to evaluate the effects of greenhouse and ground insulation on the rate and quality of biogas generation. A greenhouse ...

Remediation of water and wastewater by using engineered nanomaterials: A review.

Science.gov (United States)

Bishoge, Obadia K; Zhang, Lingling; Suntu, Shaldon L; Jin, Hui; Zewde, Abraham A; Qi, Zhongwei

2018-05-12

Nanotechnology is currently a fast-rising socioeconomic and political knowledge-based technology owing to the unique characteristics of its engineered nanomaterials. This branch of technology is useful for water and wastewater remediation. Many scientists and researchers have been conducting different studies and experiments on the applications of engineered nanomaterials at the local to international level. This review mainly aims to provide a current overview of existing knowledge on engineered nanomaterials and their applications in water and wastewater remediation. Furthermore, the present risks and challenges of nanotechnology are examined.

TOPICAL REVIEW: Stem cells engineering for cell-based therapy

Science.gov (United States)

Taupin, Philippe

2007-09-01

Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

Surgical Engineering in Cranio-Maxillofacial Surgery: A Literature Review

Directory of Open Access Journals (Sweden)

Raphael Olszewski

2012-01-01

Full Text Available A systematic review of the literature concerning surgical engineering in cranio-maxillofacial surgery was performed. APubMed search yielded 1721 papers published between 1999 and 2011. Based on the inclusion/exclusion criteria, 1428 articles were excluded after review of titles and abstracts. Atotal of 292 articles were finally selected covering the following topics: finite element analysis (n = 18, computer-assisted surgery (n = 111, rapid prototyping models (n = 41, preoperative training simulators (n = 4, surgical guides (n = 23, image-guided navigation (n = 58, augmented reality (n = 2, video tracking (n = 1, distraction osteogenesis (n = 19, robotics (n = 8, and minimal invasive surgery (n = 7. The results show that surgical engineering plays a pivotal role in the development and improvement of cranio-maxillofacial surgery. Some technologies, such as computer-assisted surgery, image-guided navigation, and three-dimensional rapid prototyping models, have reached maturity and allow for multiple clinical applications, while augmented reality, robotics, and endoscopy still need to be improved.

Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

Science.gov (United States)

Chen, Guobao; Lv, Yonggang

2015-01-01

Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

Rotary engine developments at Curtiss-Wright over the past 20 years and review of general aviation engine potential. [with direct chamber injection

Science.gov (United States)

Jones, C.

1978-01-01

The development of the rotary engine as a viable power plant capable of wide application is reviewed. Research results on the stratified charge engine with direct chamber injection are included. Emission control, reduced fuel consumption, and low noise level are among the factors discussed in terms of using the rotary engine in general aviation aircraft.

The altered glucose metabolism in tumor and a tumor acidic microenvironment associated with extracellular matrix metalloproteinase inducer and monocarboxylate transporters

Science.gov (United States)

Li, Xiaofeng; Yu, Xiaozhou; Dai, Dong; Song, Xiuyu; Xu, Wengui

2016-01-01

Extracellular matrix metalloproteinase inducer, also knowns as cluster of differentiation 147 (CD147) or basigin, is a widely distributed cell surface glycoprotein that is involved in numerous physiological and pathological functions, especially in tumor invasion and metastasis. Monocarboxylate transporters (MCTs) catalyze the proton-linked transport of monocarboxylates such as L-lactate across the plasma membrane to preserve the intracellular pH and maintain cell homeostasis. As a chaperone to some MCT isoforms, CD147 overexpression significantly contributes to the metabolic transformation of tumor. This overexpression is characterized by accelerated aerobic glycolysis and lactate efflux, and it eventually provides the tumor cells with a metabolic advantage and an invasive phenotype in the acidic tumor microenvironment. This review highlights the roles of CD147 and MCTs in tumor cell metabolism and the associated molecular mechanisms. The regulation of CD147 and MCTs may prove to be with a therapeutic potential for tumors through the metabolic modification of the tumor microenvironment. PMID:27009812

Can electronic search engines optimize screening of search results in systematic reviews: an empirical study.

Science.gov (United States)

Sampson, Margaret; Barrowman, Nicholas J; Moher, David; Clifford, Tammy J; Platt, Robert W; Morrison, Andra; Klassen, Terry P; Zhang, Li

2006-02-24

Most electronic search efforts directed at identifying primary studies for inclusion in systematic reviews rely on the optimal Boolean search features of search interfaces such as DIALOG and Ovid. Our objective is to test the ability of an Ultraseek search engine to rank MEDLINE records of the included studies of Cochrane reviews within the top half of all the records retrieved by the Boolean MEDLINE search used by the reviewers. Collections were created using the MEDLINE bibliographic records of included and excluded studies listed in the review and all records retrieved by the MEDLINE search. Records were converted to individual HTML files. Collections of records were indexed and searched through a statistical search engine, Ultraseek, using review-specific search terms. Our data sources, systematic reviews published in the Cochrane library, were included if they reported using at least one phase of the Cochrane Highly Sensitive Search Strategy (HSSS), provided citations for both included and excluded studies and conducted a meta-analysis using a binary outcome measure. Reviews were selected if they yielded between 1000-6000 records when the MEDLINE search strategy was replicated. Nine Cochrane reviews were included. Included studies within the Cochrane reviews were found within the first 500 retrieved studies more often than would be expected by chance. Across all reviews, recall of included studies into the top 500 was 0.70. There was no statistically significant difference in ranking when comparing included studies with just the subset of excluded studies listed as excluded in the published review. The relevance ranking provided by the search engine was better than expected by chance and shows promise for the preliminary evaluation of large results from Boolean searches. A statistical search engine does not appear to be able to make fine discriminations concerning the relevance of bibliographic records that have been pre-screened by systematic reviewers.

Draft audit report, human factors engineering control room design review: Saint Lucie Nuclear Power Plant, Unit No. 2

International Nuclear Information System (INIS)

Peterson, L.R.; Lappa, D.A.; Moore, J.W.

1981-01-01

A human factors engineering preliminary design review of the Saint Lucie Unit 2 control room was performed at the site on August 3 through August 7, 1981. This design review was carried out by a team from the Human Factors Engineering Branch, Division of Human Factors Safety. This report was prepared on the basis of the HFEB's review of the applicant's Preliminary Design Assessment and the human factors engineering design review/audit performed at the site. The review team included human factors consultants from BioTechnology, Inc., Falls Church, Virginia, and from Lawrence Livermore National Laboratory (University of California), Livermore, California

Critical assessment of day time traffic noise level at curbside open-air microenvironment of Kolkata City, India.

Science.gov (United States)

Kundu Chowdhury, Anirban; Debsarkar, Anupam; Chakrabarty, Shibnath

2015-01-01

The objective of the research work is to assess day time traffic noise level at curbside open-air microenvironment of Kolkata city, India under heterogeneous environmental conditions. Prevailing traffic noise level in terms of A-weighted equivalent noise level (Leq) at the microenvironment was in excess of 12.6 ± 2.1 dB(A) from the day time standard of 65 dB(A) for commercial area recommended by the Central Pollution Control Board (CPCB) of India. Noise Climate and Traffic Noise Index of the microenvironment were accounted for 13 ± 1.8 dB(A) and 88.8 ± 6.1 dB(A) respectively. A correlation analysis explored that prevailing traffic noise level of the microenvironment had weak negative (-0.21; p air temperature and relative humidity. A Varimax rotated principal component analysis explored that motorized traffic volume had moderate positive loading with background noise component (L90, L95, L99) and prevailing traffic noise level had very strong positive loading with peak noise component (L1, L5, L10). Background and peak noise component cumulatively explained 80.98 % of variance in the data set. Traffic noise level at curbside open-air microenvironment of Kolkata City was higher than the standard recommended by CPCB of India. It was highly annoying also. Air temperature and relative humidity had little influence and the peak noise component had the most significant influence on the prevailing traffic noise level at curbside open-air microenvironment. Therefore, traffic noise level at the microenvironment of the city can be reduced with careful honking and driving.

Human factors engineering design review acceptance criteria for the safety parameter display

International Nuclear Information System (INIS)

McGevna, V.; Peterson, L.R.

1981-01-01

This report contains human factors engineering design review acceptance criteria developed by the Human Factors Engineering Branch (HFEB) of the Nuclear Regulatory Commission (NRC) to use in evaluating designs of the Safety Parameter Display System (SPDS). These criteria were developed in response to the functional design criteria for the SPDS defined in NUREG-0696, Functional Criteria for Emergency Response Facilities. The purpose of this report is to identify design review acceptance criteria for the SPDS installed in the control room of a nuclear power plant. Use of computer driven cathode ray tube (CRT) displays is anticipated. General acceptance criteria for displays of plant safety status information by the SPDS are developed. In addition, specific SPDS review criteria corresponding to the SPDS functional criteria specified in NUREG-0696 are established

Human Factors Engineering Review Model for advanced nuclear power reactors

International Nuclear Information System (INIS)

O'Hara, J.; Higgins, J.; Goodman, C.; Galletti, G.: Eckenrode, R.

1993-01-01

One of the major issues to emerge from the initial design reviews under the certification process was that detailed human-systems interface (HSI) design information was not available for staff review. To address the lack of design detail issue. The Nuclear Regulatory Commission (NRC) is performing the design certification reviews based on a design process plan which describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification. Since the review of a design process is unprecedented in the nuclear industry. The criteria for review are not addressed by current regulations or guidance documents and. therefore, had to be developed. Thus, an HFE Program Review Model was developed. This paper will describe the model's rationale, scope, objectives, development, general characteristics. and application

Comparison of radiofrequency electromagnetic field exposure levels in different everyday microenvironments in an international context.

Science.gov (United States)

Sagar, Sanjay; Adem, Seid M; Struchen, Benjamin; Loughran, Sarah P; Brunjes, Michael E; Arangua, Lisa; Dalvie, Mohamed Aqiel; Croft, Rodney J; Jerrett, Michael; Moskowitz, Joel M; Kuo, Tony; Röösli, Martin

2018-05-01

The aim of this study was to quantify RF-EMF exposure applying a tested protocol of RF-EMF exposure measurements using portable devices with a high sampling rate in different microenvironments of Switzerland, Ethiopia, Nepal, South Africa, Australia and the United States of America. We used portable measurement devices for assessing RF-EMF exposure in 94 outdoor microenvironments and 18 public transport vehicles. The measurements were taken either by walking with a backpack with the devices at the height of the head and a distance of 20-30 cm from the body, or driving a car with the devices mounted on its roof, which was 170-180 cm above the ground. The measurements were taken for about 30 min while walking and about 15-20 min while driving in each microenvironment, with a sampling rate of once every 4 s (ExpoM-RF) and 5 s (EME Spy 201). Mean total RF-EMF exposure in various outdoor microenvironments varied between 0.23 V/m (non-central residential area in Switzerland) and 1.85 V/m (university area in Australia), and across modes of public transport between 0.32 V/m (bus in rural area in Switzerland) and 0.86 V/m (Auto rickshaw in urban area in Nepal). For most outdoor areas the major exposure contribution was from mobile phone base stations. Otherwise broadcasting was dominant. Uplink from mobile phone handsets was generally very small, except in Swiss trains and some Swiss buses. This study demonstrates high RF-EMF variability between the 94 selected microenvironments from all over the world. Exposure levels tended to increase with increasing urbanity. In most microenvironments downlink from mobile phone base stations is the most relevant contributor. Copyright © 2018 Elsevier Ltd. All rights reserved.

Natural Compounds Regulate Glycolysis in Hypoxic Tumor Microenvironment

Directory of Open Access Journals (Sweden)

Jian-Li Gao

2015-01-01

Full Text Available In the early twentieth century, Otto Heinrich Warburg described an elevated rate of glycolysis occurring in cancer cells, even in the presence of atmospheric oxygen (the Warburg effect. Recently it became a therapeutically interesting strategy and is considered as an emerging hallmark of cancer. Hypoxia inducible factor-1 (HIF-1 is one of the key transcription factors that play major roles in tumor glycolysis and could directly trigger Warburg effect. Thus, how to inhibit HIF-1-depended Warburg effect to assist the cancer therapy is becoming a hot issue in cancer research. In fact, HIF-1 upregulates the glucose transporters (GLUT and induces the expression of glycolytic enzymes, such as hexokinase, pyruvate kinase, and lactate dehydrogenase. So small molecules of natural origin used as GLUT, hexokinase, or pyruvate kinase isoform M2 inhibitors could represent a major challenge in the field of cancer treatment. These compounds aim to suppress tumor hypoxia induced glycolysis process to suppress the cell energy metabolism or enhance the susceptibility of tumor cells to radio- and chemotherapy. In this review, we highlight the role of natural compounds in regulating tumor glycolysis, with a main focus on the glycolysis under hypoxic tumor microenvironment.

[Design of an anesthesia and micro-environment information management system in mobile operating room].

Science.gov (United States)

Wang, Xianwen; Liu, Zhiguo; Zhang, Wenchang; Wu, Qingfu; Tan, Shulin

2013-08-01

We have designed a mobile operating room information management system. The system is composed of a client and a server. A client, consisting of a PC, medical equipments, PLC and sensors, provides the acquisition and processing of anesthesia and micro-environment data. A server is a powerful computer that stores the data of the system. The client gathers the medical device data by using the C/S mode, and analyzes the obtained HL7 messages through the class library call. The client collects the micro-environment information with PLC, and finishes the data reading with the OPC technology. Experiment results showed that the designed system could manage the patient anesthesia and micro-environment information well, and improve the efficiency of the doctors' works and the digital level of the mobile operating room.

Concentration levels and source apportionment of ultrafine particles in road microenvironments

Science.gov (United States)

Argyropoulos, G.; Samara, C.; Voutsa, D.; Kouras, A.; Manoli, E.; Voliotis, A.; Tsakis, A.; Chasapidis, L.; Konstandopoulos, A.; Eleftheriadis, K.

2016-03-01

A mobile laboratory unit (MOBILAB) with on-board instrumentation (Scanning Mobility Particle Sizer, SMPS; Ambient NOx analyzer) was used to measure size-resolved particle number concentrations (PNCs) of quasi-ultrafine particles (UFPs, 9-372 nm), along with NOx, in road microenvironments. On-road measurements were carried out in and around a large Greek urban agglomeration, the Thessaloniki Metropolitan Area (TMA). Two 2-week measurement campaigns were conducted during the warm period of 2011 and the cold period of 2012. During each sampling campaign, MOBILAB was driven through a 5-day inner-city route and a second 5-day external route covering in total a wide range of districts (urban, urban background, industrial and residential), and road types (major and minor urban roads, freeways, arterial and interurban roads). All routes were conducted during working days, in morning and in afternoon hours under real-world traffic conditions. Spatial classification of MOBILAB measurements involved the assignment of measurement points to location bins defined by the aspect ratio of adjacent urban street canyons (USCs). Source apportionment was further carried out, by applying Positive Matrix Factorization (PMF) to particle size distribution data. Apportioned PMF factors were interpreted, by employing a two-step methodology, which involved (a) statistical association of PMF factor contributions with 12 h air-mass back-trajectories ending at the TMA during MOBILAB measurements, and (b) Multiple Linear Regression (MLR) using PMF factor contributions as the dependent variables, while relative humidity, solar radiation flux, and vehicle speed were used as the independent variables. The applied data analysis showed that low-speed cruise and high-load engine operation modes are the two dominant sources of UFPs in most of the road microenvironments in the TMA, with significant contributions from background photochemical processes during the warm period, explaining the reversed

Different methods of dentin processing for application in bone tissue engineering: A systematic review.

Science.gov (United States)

Tabatabaei, Fahimeh Sadat; Tatari, Saeed; Samadi, Ramin; Moharamzadeh, Keyvan

2016-10-01

Dentin has become an interesting potential biomaterial for tissue engineering of oral hard tissues. It can be used as a scaffold or as a source of growth factors in bone tissue engineering. Different forms of dentin have been studied for their potential use as bone substitutes. Here, we systematically review different methods of dentin preparation and the efficacy of processed dentin in bone tissue engineering. An electronic search was carried out in PubMed and Scopus databases for articles published from 2000 to 2016. Studies on dentin preparation for application in bone tissue engineering were selected. The initial search yielded a total of 1045 articles, of which 37 were finally selected. Review of studies showed that demineralization was the most commonly used dentin preparation process for use in tissue engineering. Dentin extract, dentin particles (tooth ash), freeze-dried dentin, and denatured dentin are others method of dentin preparation. Based on our literature review, we can conclude that preparation procedure and the size and shape of dentin particles play an important role in its osteoinductive and osteoconductive properties. Standardization of these methods is important to draw a conclusion in this regard. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2616-2627, 2016. © 2016 Wiley Periodicals, Inc.

Effect of Interleukin 1b on rat thymus microenvironment

Directory of Open Access Journals (Sweden)

M Artico

2009-12-01

Full Text Available The effect of interleukin 1b on the thymus of control and chemically sympathectomized adult and aged rats was studied with the aim of assessing the importance of adrenergic nerve fibres (ANF in the regulation of some immunological functions.The whole thymus was removed from normal, sympathectomized (with the neurotoxin 6-OH-dopamine and treated (interleukin 1b rats. Thymic slices were stained with eosin orange (for the recognition of microanatomical details of the thymic microenvironment and with Bodian’s method for staining of nerve fibres. Histofluorescence microscopy was employed for staining ANF and immunofluorescence was used for detecting NPY-like immunoreactivity. All images were submitted to quantitative morphometrical analysis and statistical analysis of data. Moreover, the amount of proteins and noradrenaline was measured on thymic homogenates. The results indicate that in normal conditions the formation of the thymic nerve plexi in the rat is complex: the majority of ANF are destroyed after chemical sympathectomy with 6-OH-dopamine and do not change after treatment with interleukin 1b; on the contrary, treatment with interleukin 1b induces substantial changes in the fresh weight of the thymus, the thymic microenvironment, thymic nerve fibers, ANF, NPY-like positive nerve fibres, and on the total amount of proteins and noradrenaline in rat thymic tissue homogenates.Immunostimulation with interleukin 1b induces substantial changes in the whole thymus, in its microenvironment and in ANF and NPY-like nerve fibres. After chemical sympathectomy, no significant immune response was evoked by interleukin 1b, since the majority of ANF was destroyed by chemical sympathectomy.

PERFORMANCE IMPROVEMENT OF DIESEL ENGINE THROUGH VARIOUS ADVANCEMENTS IN TURBOCHARGING TECHNOLOGY: A REVIEW

OpenAIRE

A.F. Sherwani

2016-01-01

In this paper, the effect of various advancements in turbocharging technology on diesel engine power, fuel consumption, thermal efficiency, volumetric efficiency and emissions are reviewed and analyzed.Turbochargers are used throughout the automotive industry to enhance the output of an internal combustion engine without increasing the cylinder capacity. The emphasis today is to provide a feasible engineering solution to manufacturing economics and greener road vehicles. It is because of thes...

Breast cancer by proxy: can the microenvironment be both the cause and consequence?

DEFF Research Database (Denmark)

Rønnov-Jessen, Lone; Bissell, Mina J

2009-01-01

development because of the dramatic loss or aberration of basement membrane (BM) and myoepithelial cells and the gain of peritumoral myofibroblasts. We suggest that the microenvironment, defined here as all components of the mammary gland other than luminal and/or tumor epithelial cells, might be instrumental...... in maintaining organ integrity and in promoting, and at times even initiating, breast cancer development. As such, the tumor microenvironment and its constituents, alone or in combination, might serve as promising targets for therapy....

A Review on Atomization and Sprays of Biofuels for IC Engine Applications

Directory of Open Access Journals (Sweden)

Prasad Boggavarapu

2013-06-01

Full Text Available Ever increasing energy requirements, environmental concerns and energy security needs are strongly influencing engine researchers to consider renewable biofuels as alternatives to fossil fuels. Spray process being important in IC engine combustion, existing literature on various biofuel sprays is reviewed and summarized. Both experimental and computational research findings are reviewed in a detailed manner for compression ignition (CI engine sprays and briefly for spark ignition (SI engine sprays. The physics of basic atomization process of sprays from various injectors is included to highlight the most recent research findings followed by discussion highlighting the effect of physico-chemical properties on spray atomization for both biofuels and fossil fuels. Biodiesel sprays are found to penetrate faster and have narrow spray plume angle and larger droplet sizes compared to diesel. Results of analytical and computational models are shown to be useful in shedding light on the actual process of atomization. However, further studies on understanding primary atomization and the effect of fuel properties on primary atomization are required. As far as secondary atomization is concerned, changes in regimes are observed to occur at higher air-jet velocities for biodiesel compared to those of diesel. Evaporating sprays revealed that the liquid length is longer for biodiesel. Pure plant oil sprays with potential use in CI engines may require alternative injector technology due to slower breakup as compared to diesel. Application of ethanol to gasoline engines may be feasible without any modifications to port fuel injection (PFI engines. More studies are required on the application of alternative fuels to high pressure sprays used in Gasoline Direct Injection (GDI engines.

Lactic acid in tumor microenvironments causes dysfunction of NKT cells by interfering with mTOR signaling.

Science.gov (United States)

Xie, Di; Zhu, Shasha; Bai, Li

2016-12-01

Cellular metabolism has been shown to regulate differentiation and function of immune cells. Tumor associated immune cells undergo phenotypic and functional alterations due to the change of cellular metabolism in tumor microenvironments. NKT cells are good candidates for immunotherapies against tumors and have been used in several clinical trials. However, the influences of tumor microenvironments on NKT cell functions remain unclear. In our studies, lactic acid in tumor microenvironments inhibited IFNγ and IL4 productions from NKT cells, and more profound influence on IFNγ was observed. By adjusting the pH of culture medium we further showed that, dysfunction of NKT cells could simply be induced by low extracellular pH. Moreover, low extracellular pH inhibited NKT cell functions by inhibiting mammalian target of rapamycin (mTOR) signaling and nuclear translocation of promyelocytic leukemia zinc-finger (PLZF). Together, our results suggest that tumor acidic microenvironments could interfere with NKT cell functions through metabolic controls.

Review of the Space Mapping Approach to Engineering Optimization and Modeling

DEFF Research Database (Denmark)

Bakr, M. H.; Bandler, J. W.; Madsen, Kaj

2000-01-01

We review the Space Mapping (SM) concept and its applications in engineering optimization and modeling. The aim of SM is to avoid computationally expensive calculations encountered in simulating an engineering system. The existence of less accurate but fast physically-based models is exploited. S......-based Modeling (SMM). These include Space Derivative Mapping (SDM), Generalized Space Mapping (GSM) and Space Mapping-based Neuromodeling (SMN). Finally, we address open points for research and future development....

T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments.

Science.gov (United States)

Hawkins, Edwin D; Duarte, Delfim; Akinduro, Olufolake; Khorshed, Reema A; Passaro, Diana; Nowicka, Malgorzata; Straszkowski, Lenny; Scott, Mark K; Rothery, Steve; Ruivo, Nicola; Foster, Katie; Waibel, Michaela; Johnstone, Ricky W; Harrison, Simon J; Westerman, David A; Quach, Hang; Gribben, John; Robinson, Mark D; Purton, Louise E; Bonnet, Dominique; Lo Celso, Cristina

2016-10-27

It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment

Persistent injury-associated anemia: the role of the bone marrow microenvironment.

Science.gov (United States)

Millar, Jessica K; Kannan, Kolenkode B; Loftus, Tyler J; Alamo, Ines G; Plazas, Jessica; Efron, Philip A; Mohr, Alicia M

2017-06-15

The regulation of erythropoiesis involves hematopoietic progenitor cells, bone marrow stroma, and the microenvironment. Following severe injury, a hypercatecholamine state develops that is associated with increased mobilization of hematopoietic progenitor cells to peripheral blood and decreased growth of bone marrow erythroid progenitor cells that manifests clinically as a persistent injury-associated anemia. Changes within the bone marrow microenvironment influence the development of erythroid progenitor cells. Therefore, we sought to determine the effects of lung contusion, hemorrhagic shock, and chronic stress on the hematopoietic cytokine response. Bone marrow was obtained from male Sprague-Dawley rats (n = 6/group) killed 7 d after lung contusion followed by hemorrhagic shock (LCHS) or LCHS followed by daily chronic restraint stress (LCHS/CS). End point polymerase chain reaction was performed for interleukin-1β, interleukin-10, stem cell factor, transforming growth factor-β, high-mobility group box-1 (HMGB-1), and B-cell lymphoma-extra large. Seven days following LCHS and LCHS/CS, bone marrow expression of prohematopoietic cytokines (interleukin-1β, interleukin-10, stem cell factor, and transforming growth factor-β) was significantly decreased, and bone marrow expression of HMGB-1 was significantly increased. B-cell lymphoma-extra large bone marrow expression was not affected by LCHS or LCHS/CS (naïve: 44 ± 12, LCHS: 44 ± 12, LCHS/CS: 37 ± 1, all P > 0.05). The bone marrow microenvironment was significantly altered following severe trauma in a rodent model. Prohematopoietic cytokines were downregulated, and the proinflammatory cytokine HMGB-1 had increased bone marrow expression. Modulation of the bone marrow microenvironment may represent a therapeutic strategy following severe trauma to alleviate persistent injury-associated anemia. Copyright © 2017 Elsevier Inc. All rights reserved.

77 FR 3844 - Agency Information Collection (Architect-Engineer Fee Proposal) Activity Under OMB Review

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2012-01-25

... DEPARTMENT OF VETERANS AFFAIRS [OMB Control No. 2900-0208] Agency Information Collection (Architect--Engineer Fee Proposal) Activity Under OMB Review AGENCY: Veterans Health Administration... . Please refer to ``OMB Control No. 2900-0208.'' SUPPLEMENTARY INFORMATION: Titles: a. Architect--Engineer...

Differential effects of the extracellular microenvironment on human embryonic stem cell differentiation into keratinocytes and their subsequent replicative life span.

Science.gov (United States)

Movahednia, Mohammad Mehdi; Kidwai, Fahad Karim; Zou, Yu; Tong, Huei Jinn; Liu, Xiaochen; Islam, Intekhab; Toh, Wei Seong; Raghunath, Michael; Cao, Tong

2015-04-01

Culture microenvironment plays a critical role in the propagation and differentiation of human embryonic stem cells (hESCs) and their differentiated progenies. Although high efficiency of hESC differentiation to keratinocytes (hESC-Kert) has been achieved, little is known regarding the effects of early culture microenvironment and pertinent extracellular matrix (ECM) interactions during epidermal commitment on subsequent proliferative capacity of hESC-Kert. The aim of this study is to evaluate the effects of the different ECM microenvironments during hESC differentiation on subsequent replicative life span of hESC-Kert. In doing so, H1-hESCs were differentiated to keratinocytes (H1-Kert) in two differentiation systems. The first system employed autologous fibroblast feeder support, in which keratinocytes (H1-Kert(ACC)) were derived by coculture of hESCs with hESC-derived fibroblasts (H1-ebFs). The second system employed a novel decellularized matrix from H1-ebFs to create a dermoepidermal junction-like (DEJ) matrix. H1-Kert(AFF) were derived by differentiation of hESCs on the feeder-free system employing the DEJ matrix. Our study indicated that the feeder-free system with the use of DEJ matrix was more efficient in differentiation of hESCs toward epidermal progenitors. However, the feeder-free system was not sufficient to support the subsequent replicative capacity of differentiated keratinocytes. Of note, H1-Kert(AFF) showed limited replicative capacity with reduced telomere length and early cellular senescence. We further showed that the lack of cell-cell interactions during epidermal commitment led to heightened production of TGF-β1 by hESC-Kert during extended culture, which in turn was responsible for resulting in the limited replicative life span with cellular senescence of hESC-Kert derived under the feeder-free culture system. This study highlights for the first time the importance of the culture microenvironment and cell-ECM interactions during

Quality of Design, Analysis and Reporting of Software Engineering Experiments:A Systematic Review

OpenAIRE

By Kampenes, Vigdis

2007-01-01

Background: Like any research discipline, software engineering research must be of a certain quality to be valuable. High quality research in software engineering ensures that knowledge is accumulated and helpful advice is given to the industry. One way of assessing research quality is to conduct systematic reviews of the published research literature. Objective: The purpose of this work was to assess the quality of published experiments in software engineering with respect to the validit...

Multiple Myeloma Macrophages: Pivotal Players in the Tumor Microenvironment

Directory of Open Access Journals (Sweden)

Simona Berardi

2013-01-01

Full Text Available Tumor microenvironment is essential for multiple myeloma (MM growth, progression, and drug resistance through provision of survival signals and secretion of growth and proangiogenic factors. This paper examines the importance of macrophages within MM bone marrow (BM microenvironment, referred to as MM-associated macrophages, as a potential niche component that supports tumor plasma cells. These macrophages are derived from peripheral blood monocytes recruited into the tumor. Upon activation by MM plasma cells and mesenchymal stromal cells, macrophages can release growth factors, proteolytic enzymes, cytokines, and inflammatory mediators that promote plasma cell growth and survival. Macrophages promote tumor progression through several mechanisms including angiogenesis, growth, and drug resistance. Indeed, these macrophages are essential for the induction of an angiogenic response through vasculogenic mimicry, and this ability proceeds in step with progression of the plasma cell tumors. Data suggest that macrophages play an important role in the biology and survival of patients with MM, and they may be a target for the MM antivascular management.

A review of Curtiss-Wright rotary engine developments with respect to general aviation potential

Science.gov (United States)

Jones, C.

1979-01-01

Aviation related rotary (Wankel-type) engine tests, possible growth directions and relevant developments at Curtiss-Wright have been reviewed. Automotive rotary engines including stratified charge are described and flight test results of rotary aircraft engines are presented. The current 300 HP engine prototype shows basic durability and competitive performance potential. Recent parallel developments have separately confirmed the geometric advantages of the rotary engine for direct injected unthrottled stratified charge. Specific fuel consumption equal to or better than pre- or swirl-chamber diesels, low emission and multi-fuel capability have been shown by rig tests of similar rotary engine.

Adipose, Bone, and Myeloma: Contributions from the Microenvironment.

Science.gov (United States)

McDonald, Michelle M; Fairfield, Heather; Falank, Carolyne; Reagan, Michaela R

2017-05-01

Researchers globally are working towards finding a cure for multiple myeloma (MM), a destructive blood cancer diagnosed yearly in ~750,000 people worldwide (Podar et al. in Expert Opin Emerg Drugs 14:99-127, 2009). Although MM targets multiple organ systems, it is the devastating skeletal destruction experienced by over 90 % of patients that often most severely impacts patient morbidity, pain, and quality of life. Preventing bone disease is therefore a priority in MM treatment, and understanding how and why myeloma cells target the bone marrow (BM) is fundamental to this process. This review focuses on a key area of MM research: the contributions of the bone microenvironment to disease origins, progression, and drug resistance. We describe some of the key cell types in the BM niche: osteoclasts, osteoblasts, osteocytes, adipocytes, and mesenchymal stem cells. We then focus on how these key cellular players are, or could be, regulating a range of disease-related processes spanning MM growth, drug resistance, and bone disease (including osteolysis, fracture, and hypercalcemia). We summarize the literature regarding MM-bone cell and MM-adipocyte relationships and subsequent phenotypic changes or adaptations in MM cells, with the aim of providing a deeper understanding of how myeloma cells grow in the skeleton to cause bone destruction. We identify avenues and therapies that intervene in these networks to stop tumor growth and/or induce bone regeneration. Overall, we aim to illustrate how novel therapeutic target molecules, proteins, and cellular mediators may offer new avenues to attack this disease while reviewing currently utilized therapies.

Human factors engineering plan for reviewing nuclear plant modernization programs

International Nuclear Information System (INIS)

O'Hara, John; Higgins, James

2004-12-01

The Swedish Nuclear Power Inspectorate reviews the human factors engineering (HFE) aspects of nuclear power plants (NPPs) involved in the modernization of the plant systems and control rooms. The purpose of a HFE review is to help ensure personnel and public safety by verifying that accepted HFE practices and guidelines are incorporated into the program and nuclear power plant design. Such a review helps to ensure the HFE aspects of an NPP are developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The review addresses eleven HFE elements: HFE Program Management, Operating Experience Review, Functional Requirements Analysis and Allocation, Task Analysis, Staffing, Human Reliability Analysis, Human-System Interface Design, Procedure Development, Training Program Development, Human Factors Verification and Validation, and Design Implementation

Human factors engineering plan for reviewing nuclear plant modernization programs

Energy Technology Data Exchange (ETDEWEB)

O' Hara, John; Higgins, James [Brookhaven National Laboratory, Upton, NY (United States)

2004-12-01

The Swedish Nuclear Power Inspectorate reviews the human factors engineering (HFE) aspects of nuclear power plants (NPPs) involved in the modernization of the plant systems and control rooms. The purpose of a HFE review is to help ensure personnel and public safety by verifying that accepted HFE practices and guidelines are incorporated into the program and nuclear power plant design. Such a review helps to ensure the HFE aspects of an NPP are developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The review addresses eleven HFE elements: HFE Program Management, Operating Experience Review, Functional Requirements Analysis and Allocation, Task Analysis, Staffing, Human Reliability Analysis, Human-System Interface Design, Procedure Development, Training Program Development, Human Factors Verification and Validation, and Design Implementation.

Effects of microenvironment on growth and differentiation of human dental pulp cells

Science.gov (United States)

Datko, Laura Christine

Dental pulp stem cells (DPSCs) have recently been described as a potential stem cell source for various regenerative medicine and tissue engineering applications. They appear to be multipotent, however more characterization is necessary to determine the true potential of these cells. An important aspect of using DPSCs, or any stem cell type, tissue engineering application is the microenvironment within the construct. The microenvironment could include construct mechanical properties, construct composition, and 3D dynamic conditions in vivo. This work aims to study those specific microenvironment effects on DPSCs. To determine the effects of mechanical properties of the substrate on DPSCs, they were seeded on polyacrylamide (PA) gels of different elastic moduli. These gels ranged from 3 kPa to 75 kPa and a glass coverslip was used as a control. They were also exposed to either standard stem cell media or an osteogenic differentiation media, to determine the potential of the DPSCs for osteogenic/odontogenic differentiation. The cultures were analyzed for morphological changes, osteopontin production, alkaline phosphatase (ALP) production, and mineralization. The results showed that the DPSCs adhered well to the PA gels for the first few days in culture, but by day 7, they were starting to detach from the PA gels and only remain viable in gel defects or along the edges. This selective growth was also reflected in the mineralization, which only occurred in areas of confluence for the cells on the PA gels. Interestingly, all cultures produced osteopontin and ALP, however by the end of the experiment, the cells cultured on glass had the highest ALP production. It appeared that without the addition of growth factors to induce other cell lineages, DPSCs defaulted to an osteogenic/odontogenic lineage. To determine the effect of mineral composition, preliminary studies were done on bone marrow stromal cells (BMSCs) and 7F2 osteoblasts. These two cell types were exposed to

Local iron homeostasis in the breast ductal carcinoma microenvironment

International Nuclear Information System (INIS)

Marques, Oriana; Porto, Graça; Rêma, Alexandra; Faria, Fátima; Cruz Paula, Arnaud; Gomez-Lazaro, Maria; Silva, Paula; Martins da Silva, Berta; Lopes, Carlos

2016-01-01

While the deregulation of iron homeostasis in breast epithelial cells is acknowledged, iron-related alterations in stromal inflammatory cells from the tumor microenvironment have not been explored. Immunohistochemistry for hepcidin, ferroportin 1 (FPN1), transferrin receptor 1 (TFR1) and ferritin (FT) was performed in primary breast tissues and axillary lymph nodes in order to dissect the iron-profiles of epithelial cells, lymphocytes and macrophages. Furthermore, breast carcinoma core biopsies frozen in optimum cutting temperature (OCT) compound were subjected to imaging flow cytometry to confirm FPN1 expression in the cell types previously evaluated and determine its cellular localization. We confirm previous results by showing that breast cancer epithelial cells present an ‘iron-utilization phenotype’ with an increased expression of hepcidin and TFR1, and decreased expression of FT. On the other hand, lymphocytes and macrophages infiltrating primary tumors and from metastized lymph nodes display an ‘iron-donor’ phenotype, with increased expression of FPN1 and FT, concomitant with an activation profile reflected by a higher expression of TFR1 and hepcidin. A higher percentage of breast carcinomas, compared to control mastectomy samples, present iron accumulation in stromal inflammatory cells, suggesting that these cells may constitute an effective tissue iron reservoir. Additionally, not only the deregulated expression of iron-related proteins in epithelial cells, but also on lymphocytes and macrophages, are associated with clinicopathological markers of breast cancer poor prognosis, such as negative hormone receptor status and tumor size. The present results reinforce the importance of analyzing the tumor microenvironment in breast cancer, extending the contribution of immune cells to local iron homeostasis in the tumor microenvironment context

Tumor microenvironment in invasive lobular carcinoma: possible therapeutic targets.

Science.gov (United States)

Nakagawa, Saki; Miki, Yasuhiro; Miyashita, Minoru; Hata, Shuko; Takahashi, Yayoi; Rai, Yoshiaki; Sagara, Yasuaki; Ohi, Yasuyo; Hirakawa, Hisashi; Tamaki, Kentaro; Ishida, Takanori; Watanabe, Mika; Suzuki, Takashi; Ohuchi, Noriaki; Sasano, Hironobu

2016-01-01

Invasive ductal and lobular carcinomas (IDC and ILC) are the two most common histological types of breast cancer, and have been considered to develop from terminal duct lobular unit but their molecular, pathological, and clinical features are markedly different between them. These differences could be due to different mechanisms of carcinogenesis and tumor microenvironment, especially cancer-associated fibroblasts (CAFs) but little has been explored in this aspect. Therefore, in this study, we evaluated the status of angiogenesis, maturation of intratumoral microvessels, and proliferation of CAFs using immunohistochemistry and PCR array analysis to explore the differences of tumor microenvironment between ILC and IDC. We studied grade- and age-matched, luminal-like ILC and IDC. We immunolocalized CD34 and αSMA for an evaluation of CAFs and CD31, Vasohibin-1, a specific marker of proliferative endothelial cells and nestin, a marker of pericytes for studying the status of proliferation and maturation of intratumoral microvessel. We also performed PCR array analysis to evaluate angiogenic factors in tumor stromal components. The number of CAFs, microvessel density, and vasohibin-1/CD31 positive ratio were all significantly higher in ILC than IDC but nestin immunoreactivity in intratumoral microvessel was significantly lower in ILC. These results did indicate that proliferation of CAFs and endothelial cells was more pronounced in ILC than IDC but newly formed microvessels were less mature than those in IDC. PCR array analysis also revealed that IGF-1 expression was higher in ILC than IDC. This is the first study to demonstrate the differences of tumor microenvironment including CAFs and proliferation and maturation of intratumoral vessels between ILC and IDC.

Recent Advances in Crystal Engineering from Nanoscience Views: A Brief Review

Directory of Open Access Journals (Sweden)

Marzieh Arab Fashapoyeh

2017-01-01

Full Text Available Crystal engineering has recently emerged as a method of choice for the design and construction of organic as well as metal-organic functional materials. Crystal engineering attempts to establish packing trends in whole families of compounds and seeks to establish connections between structure and function. The utility of crystal engineering has also been expanded to the nanoscience and the development of nanomaterials. The crystal engineering of materials on the nanoscale has attracted attention from various fields of research. Using bottom-up assembly strategies, a wide range of functional systems can be accessed. Materials of nanometer-scale dimensions having unique physicochemical properties are of great interest in various fields such as synthetic chemistry, materials science, catalysis and medicine. This review concerns to the recent advances in crystal engineering from nanoscience views. This study was conducted in four categories; nanococrystals, nano metal-organic frameworks, composites of polyoxometalates and also some of the nanocarbons.

A Review of Three-Dimensional Printing in Tissue Engineering.

Science.gov (United States)

Sears, Nick A; Seshadri, Dhruv R; Dhavalikar, Prachi S; Cosgriff-Hernandez, Elizabeth

2016-08-01

Recent advances in three-dimensional (3D) printing technologies have led to a rapid expansion of applications from the creation of anatomical training models for complex surgical procedures to the printing of tissue engineering constructs. In addition to achieving the macroscale geometry of organs and tissues, a print layer thickness as small as 20 μm allows for reproduction of the microarchitectures of bone and other tissues. Techniques with even higher precision are currently being investigated to enable reproduction of smaller tissue features such as hepatic lobules. Current research in tissue engineering focuses on the development of compatible methods (printers) and materials (bioinks) that are capable of producing biomimetic scaffolds. In this review, an overview of current 3D printing techniques used in tissue engineering is provided with an emphasis on the printing mechanism and the resultant scaffold characteristics. Current practical challenges and technical limitations are emphasized and future trends of bioprinting are discussed.

Tissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a “Watch-and-Wait” Approach to Cancer

Science.gov (United States)

Li, Shengwen Calvin; Vu, Long T.; Luo, Jane Jianying; Zhong, Jiang F.; Li, Zhongjun; Dethlefs, Brent A; Loudon, William G.; Kabeer, Mustafa H.

2017-01-01

Targeting the tumor microenvironment (TME) through which cancer stem cells (CSCs) crosstalk for cancer initiation and progression, may open up new treatments different from those centered on the original hallmarks of cancer genetics thereby implying a new approach for suppression of TME-driven activation of CSCs. Cancer is dynamic, heterogeneous, evolving with the TME and can be influenced by tissue-specific elasticity. One of the mediators and modulators of the crosstalk between CSCs and mechanical forces is miRNA, which can be developmentally regulated, in a tissue- and cell-specific manner. Here, based on our previous data, we provide a framework through which such gene expression changes in response to external mechanical forces can be understood during cancer progression. Recognizing the ways mechanical forces regulate and affect intracellular signals with applications in cancer stem cell biology. Such TME-targeted pathways shed new light on strategies for attacking cancer stem cells with fewer side effects than traditional gene-based treatments for cancer, requiring a “watch-and-wait” approach. We attempt to address both normal brain microenvironment and tumor microenvironment as both works together, intertwining in pathology and physiology – a balance that needs to be maintained for the “watch-and-wait” approach to cancer. Thus, this review connected the subjects of tissue elasticity, tumor microenvironment, epigenetic of miRNAs, and stem-cell biology that are very relevant in cancer research and therapy. It attempts to unify apparently separate entities in a complex biological web, network, and system in a realistic and practical manner, i.e., to bridge basic research with clinical application. PMID:28270089

Tsallis Entropy Theory for Modeling in Water Engineering: A Review

Directory of Open Access Journals (Sweden)

Vijay P. Singh

2017-11-01

Full Text Available Water engineering is an amalgam of engineering (e.g., hydraulics, hydrology, irrigation, ecosystems, environment, water resources and non-engineering (e.g., social, economic, political aspects that are needed for planning, designing and managing water systems. These aspects and the associated issues have been dealt with in the literature using different techniques that are based on different concepts and assumptions. A fundamental question that still remains is: Can we develop a unifying theory for addressing these? The second law of thermodynamics permits us to develop a theory that helps address these in a unified manner. This theory can be referred to as the entropy theory. The thermodynamic entropy theory is analogous to the Shannon entropy or the information theory. Perhaps, the most popular generalization of the Shannon entropy is the Tsallis entropy. The Tsallis entropy has been applied to a wide spectrum of problems in water engineering. This paper provides an overview of Tsallis entropy theory in water engineering. After some basic description of entropy and Tsallis entropy, a review of its applications in water engineering is presented, based on three types of problems: (1 problems requiring entropy maximization; (2 problems requiring coupling Tsallis entropy theory with another theory; and (3 problems involving physical relations.

A comprehensive review of cryogels and their roles in tissue engineering applications.

Science.gov (United States)

Hixon, Katherine R; Lu, Tracy; Sell, Scott A

2017-10-15

The extracellular matrix is fundamental in providing an appropriate environment for cell interaction and signaling to occur. Replicating such a matrix is advantageous in the support of tissue ingrowth and regeneration through the field of tissue engineering. While scaffolds can be fabricated in many ways, cryogels have recently become a popular approach due to their macroporous structure and durability. Produced through the crosslinking of gel precursors followed by a subsequent controlled freeze/thaw cycle, the resulting cryogel provides a unique, sponge-like structure. Therefore, cryogels have proven advantageous for many tissue engineering applications including roles in bioreactor systems, cell separation, and scaffolding. Specifically, the matrix has been demonstrated to encourage the production of various molecules, such as antibodies, and has also been used for cryopreservation. Cryogels can pose as a bioreactor for the expansion of cell lines, as well as a vehicle for cell separation. Lastly, this matrix has shown excellent potential as a tissue engineered scaffold, encouraging regrowth at numerous damaged tissue sites in vivo. This review will briefly discuss the fabrication of cryogels, with an emphasis placed on their application in various facets of tissue engineering to provide an overview of this unique scaffold's past and future roles. Cryogels are unique scaffolds produced through the controlled freezing and thawing of a polymer solution. There is an ever-growing body of literature that demonstrates their applicability in the realm of tissue engineering as extracellular matrix analogue scaffolds; with extensive information having been provided regarding the fabrication, porosity, and mechanical integrity of the scaffolds. Additionally, cryogels have been reviewed with respect to their role in bioseparation and as cellular incubators. This all-inclusive view of the roles that cryogels can play is critical to advancing the technology and expanding its

Review of methods for the integration of reliability and design engineering

International Nuclear Information System (INIS)

Reilly, J.T.

1978-03-01

A review of methods for the integration of reliability and design engineering was carried out to establish a reliability program philosophy, an initial set of methods, and procedures to be used by both the designer and reliability analyst. The report outlines a set of procedures which implements a philosophy that requires increased involvement by the designer in reliability analysis. Discussions of each method reviewed include examples of its application

Functional live cell imaging of the pulmonary neuroepithelial body microenvironment

NARCIS (Netherlands)

De Proost, Ian; Pintelon, Isabel; Brouns, Inge; Kroese, A; Riccardi, Daniela; Kemp, Paul J.; Timmermans, Jean-Pierre; Adriaensen, Dirk

Pulmonary neuroepithelial bodies (NEBs) are densely innervated groups of neuroendocrine cells invariably accompanied by Clara-like cells. Together with NEBs, Clara-like cells form the so-called "NEB microenvironment," which recently has been assigned a potential pulmonary stem cell niche. Conclusive

Immunotherapeutic Potential of Oncolytic H-1 Parvovirus: Hints of Glioblastoma Microenvironment Conversion towards Immunogenicity.

Science.gov (United States)

Angelova, Assia L; Barf, Milena; Geletneky, Karsten; Unterberg, Andreas; Rommelaere, Jean

2017-12-15

Glioblastoma, one of the most aggressive primary brain tumors, is characterized by highly immunosuppressive microenvironment. This contributes to glioblastoma resistance to standard treatment modalities and allows tumor growth and recurrence. Several immune-targeted approaches have been recently developed and are currently under preclinical and clinical investigation. Oncolytic viruses, including the autonomous protoparvovirus H-1 (H-1PV), show great promise as novel immunotherapeutic tools. In a first phase I/IIa clinical trial (ParvOryx01), H-1PV was safe and well tolerated when locally or systemically administered to recurrent glioblastoma patients. The virus was able to cross the blood-brain (tumor) barrier after intravenous infusion. Importantly, H-1PV treatment of glioblastoma patients was associated with immunogenic changes in the tumor microenvironment. Tumor infiltration with activated cytotoxic T cells, induction of cathepsin B and inducible nitric oxide (NO) synthase (iNOS) expression in tumor-associated microglia/macrophages (TAM), and accumulation of activated TAM in cluster of differentiation (CD) 40 ligand (CD40L)-positive glioblastoma regions was detected. These are the first-in-human observations of H-1PV capacity to switch the immunosuppressed tumor microenvironment towards immunogenicity. Based on this pilot study, we present a tentative model of H-1PV-mediated modulation of glioblastoma microenvironment and propose a combinatorial therapeutic approach taking advantage of H-1PV-induced microglia/macrophage activation for further (pre)clinical testing.

The effects of electric fields on charged molecules and particles in individual microenvironments

Science.gov (United States)

Jamieson, K. S.; ApSimon, H. M.; Jamieson, S. S.; Bell, J. N. B.; Yost, M. G.

Measurements of small air ion concentrations, electrostatic potential and AC electric field strengths were taken in an office setting to investigate the link between electric fields and charged molecule and particle concentrations in individual microenvironments. The results obtained indicate that the electromagnetic environments individuals can be exposed to whilst indoors can often bear little resemblance to those experienced outdoors in nature, and that many individuals may spend large periods of their time in "Faraday cage"-like conditions exposed to inappropriate levels and types of electric fields that can reduce localised concentrations of biologically essential and microbiocidal small air ions. Such conditions may escalate their risk of infection from airborne contaminants, including microbes, whilst increasing localised surface contamination. The degree of "electro-pollution" that individuals are exposed to was shown to be influenced by the type of microenvironment they occupy, with it being possible for very different types of microenvironment to exist within the same room. It is suggested that adopting suitable electromagnetic hygiene/productivity guidelines that seek to replicate the beneficial effects created by natural environments may greatly mitigate such problems.

Construction of extracellular microenvironment to improve surface endothelialization of NiTi alloy substrate

Energy Technology Data Exchange (ETDEWEB)

Liu, Peng, E-mail: liupeng79@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433 (China); Zhao, Yongchun; Yan, Ying; Hu, Yan; Yang, Weihu [Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Cai, Kaiyong, E-mail: kaiyong_cai@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

2015-10-01

To mimic extracellular microenvironment of endothelial cell, a bioactive multilayered structure of gelatin/chitosan pair, embedding with vascular endothelial growth factor (VEGF), was constructed onto NiTi alloy substrate surface via a layer-by-layer assembly technique. The successful fabrication of the multilayered structure was demonstrated by scanning electron microscopy, atomic force microscopy, contact angle measurement, attenuated total reflection-fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, respectively. The growth behaviors of endothelial cells on various NiTi alloy substrates were investigated in vitro. Cytoskeleton observation, MTT assay, and wound healing assay proved that the VEGF-embedded multilayer structure positively stimulated adhesion, proliferation and motogenic responses of endothelial cells. More importantly, the present system promoted the nitric oxide production of endothelial cells. The approach affords an alternative to construct extracellular microenvironment for improving surface endothelialization of a cardiovascular implant. - Highlights: • Biofunctional multilayer films mimicking extracellular microenvironment were successfully fabricated. • Multilayered structure stimulated the biological responses of endothelial cells. • The approach affords an efficient approach for surface endothelialization of stent implant.

Natural product derivative BIO promotes recovery after myocardial infarction via unique modulation of the cardiac microenvironment

Science.gov (United States)

Kim, Yong Sook; Jeong, Hye-yun; Kim, Ah Ra; Kim, Woong-Hee; Cho, Haaglim; Um, JungIn; Seo, Youngha; Kang, Wan Seok; Jin, Suk-Won; Kim, Min Chul; Kim, Yong-Chul; Jung, Da-Woon; Williams, Darren R.; Ahn, Youngkeun

2016-01-01

The cardiac microenvironment includes cardiomyocytes, fibroblasts and macrophages, which regulate remodeling after myocardial infarction (MI). Targeting this microenvironment is a novel therapeutic approach for MI. We found that the natural compound derivative, BIO ((2′Z,3′E)-6-Bromoindirubin-3′-oxime) modulated the cardiac microenvironment to exert a therapeutic effect on MI. Using a series of co-culture studies, BIO induced proliferation in cardiomyocytes and inhibited proliferation in cardiac fibroblasts. BIO produced multiple anti-fibrotic effects in cardiac fibroblasts. In macrophages, BIO inhibited the expression of pro-inflammatory factors. Significantly, BIO modulated the molecular crosstalk between cardiac fibroblasts and differentiating macrophages to induce polarization to the anti-inflammatory M2 phenotype. In the optically transparent zebrafish-based heart failure model, BIO induced cardiomyocyte proliferation and completely recovered survival rate. BIO is a known glycogen synthase kinase-3β inhibitor, but these effects could not be recapitulated using the classical inhibitor, lithium chloride; indicating novel therapeutic effects of BIO. We identified the mechanism of BIO as differential modulation of p27 protein expression and potent induction of anti-inflammatory interleukin-10. In a rat MI model, BIO reduced fibrosis and improved cardiac performance. Histological analysis revealed modulation of the cardiac microenvironment by BIO, with increased presence of anti-inflammatory M2 macrophages. Our results demonstrate that BIO produces unique effects in the cardiac microenvironment to promote recovery post-MI. PMID:27510556

Gene therapy with growth factors for periodontal tissue engineering–A review

Science.gov (United States)

Gupta, Shipra; Mahendra, Aneet

2012-01-01

The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. A challenge faced by periodontal therapy is the predictable regeneration of periodontal tissues lost as a consequence of disease. Growth factors are critical to the development, maturation, maintenance and repair of oral tissues as they establish an extra-cellular environment that is conducive to cell and tissue growth. Tissue engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. The aim of this paper is to review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Various such materials have been formulated into devices that can be used as vehicles for delivery of cells, growth factors and DNA. Different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral and tooth supporting structure. Key words: Periodontal disease, gene therapy, regeneration, tissue repair, growth factors, tissue engineering. PMID:22143705

Passive Techniques for Fan Noise Reduction in New Turbofan Engines: Review

Directory of Open Access Journals (Sweden)

M.Gorj-Bandpy

2013-03-01

Full Text Available Among the various environmental concerns, the aircraft noise item has been constantly growing in importance over the past years. Measures for its reduction at the source as well its mitigation around airports must take into account aspects of medicine and technical design as well as legal and land use planning aspects. Fan noise is one of the principal noise sources in turbofan aero-engines. In this paper a review of the main technologies employed for the reduction of fan noise turbofan engines is presented.

Hypoxia and Stem Cell-Based Engineering of Mesenchymal Tissues

OpenAIRE

Ma, Teng; Grayson, Warren L.; Fröhlich, Mirjam; Vunjak-Novakovic, Gordana

2009-01-01

Stem cells have the ability for prolonged self-renewal and differentiation into mature cells of various lineages, which makes them important cell sources for tissue engineering applications. Their remarkable ability to replenish and differentiate in vivo is regulated by both intrinsic and extrinsic cellular mechanisms. The anatomical location where the stem cells reside, known as the “stem cell niche or microenvironment,” provides signals conducive to the maintenance of definitive stem cell p...

CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment.

Science.gov (United States)

Han, Yan; Wu, Chunlei; Wang, Jing; Liu, Na

2017-05-01

The major cause of death in osteosarcoma is the invasion and metastasis. Better understanding of the molecular mechanism of osteosarcoma invasion is essential in developing effective tumor-suppressive therapies. Interaction between chemokine receptors plays a crucial role in regulating osteosarcoma invasion. Here, we investigated the relationship between CXCR7 and CXCR4 in osteosarcoma invasion induced by bone marrow microenvironment. Human bone marrow mesenchymal stem cells were co-cultured with osteosarcoma cells to mimic actual bone marrow microenvironment. Osteosarcoma cell invasion and CXCL12/CXCR4 activation were observed within this co-culture model. Interestingly, in this co-culture model, osteosarcoma cell invasion was not inhibited by suppressing CXCR4 expression with neutralizing antibody or specific inhibitor AMD3100. Downstream signaling extracellular signal-regulated kinase and signal transducer and activator of transcription 3 were not significantly affected by CXCR4 inhibition. However, suppressing CXCR4 led to CXCR7 upregulation. Constitutive expression of CXCR7 could maintain osteosarcoma cell invasion when CXCR4 was suppressed. Simultaneously, inhibiting CXCR4 and CXCR7 compromised osteosarcoma invasion in co-culture system and suppressed extracellular signal-regulated kinase and signal transducer and activator of transcription 3 signals. Moreover, bone marrow microenvironment, not CXCL12 alone, is required for CXCR7 activation after CXCR4 suppression. Taken together, suppressing CXCR4 is not enough to impede osteosarcoma invasion in bone marrow microenvironment since CXCR7 is activated to sustain invasion. Therefore, inhibiting both CXCR4 and CXCR7 could be a promising strategy in controlling osteosarcoma invasion.

Genotoxicity of metal based engineered nanoparticles in aquatic organisms: A review

CSIR Research Space (South Africa)

Mahaye, Ntombikayise

2017-07-01

Full Text Available Engineered nanoparticles (ENPs) are an emerging class of environmental contaminants, but are generally found in very low concentrations and are therefore likely to exert sub-lethal effects on aquatic organisms. In this review, we: (i) highlight key...

Nanocarbons in Electrospun Polymeric Nanomats for Tissue Engineering: A Review

Directory of Open Access Journals (Sweden)

Roberto Scaffaro

2017-02-01

Full Text Available Electrospinning is a versatile process technology, exploited for the production of fibers with varying diameters, ranging from nano- to micro-scale, particularly useful for a wide range of applications. Among these, tissue engineering is particularly relevant to this technology since electrospun fibers offer topological structure features similar to the native extracellular matrix, thus providing an excellent environment for the growth of cells and tissues. Recently, nanocarbons have been emerging as promising fillers for biopolymeric nanofibrous scaffolds. In fact, they offer interesting physicochemical properties due to their small size, large surface area, high electrical conductivity and ability to interface/interact with the cells/tissues. Nevertheless, their biocompatibility is currently under debate and strictly correlated to their surface characteristics, in terms of chemical composition, hydrophilicity and roughness. Among the several nanofibrous scaffolds prepared by electrospinning, biopolymer/nanocarbons systems exhibit huge potential applications, since they combine the features of the matrix with those determined by the nanocarbons, such as conductivity and improved bioactivity. Furthermore, combining nanocarbons and electrospinning allows designing structures with engineered patterns at both nano- and microscale level. This article presents a comprehensive review of various types of electrospun polymer-nanocarbon currently used for tissue engineering applications. Furthermore, the differences among graphene, carbon nanotubes, nanodiamonds and fullerenes and their effect on the ultimate properties of the polymer-based nanofibrous scaffolds is elucidated and critically reviewed.

Differential immune microenvironments and response to immune checkpoint blockade amongst molecular subtypes of murine medulloblastoma

Science.gov (United States)

Pham, Christina D.; Flores, Catherine; Yang, Changlin; Pinheiro, Elaine M.; Yearley, Jennifer H.; Sayour, Elias J.; Pei, Yanxin; Moore, Colin; McLendon, Roger E.; Huang, Jianping; Sampson, John H.; Wechsler-Reya, Robert; Mitchell, Duane A.

2016-01-01

PURPOSE Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma (MB), the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. To address this, we adapted two syngeneic animal models of human Sonic Hedgehog (SHH)-driven and Group 3 MB for preclinical evaluation in immunocompetent C57BL/6 mice. METHODS AND RESULTS Multicolor flow cytometric analyses were used to phenotype and characterize immune infiltrating cells within established cerebellar tumors. We observed significantly higher percentages of dendritic cells, infiltrating lymphocytes, myeloid derived suppressor cells and tumor-associated macrophages in murine SHH model tumors compared with Group 3 tumors. However, murine Group 3 tumors had higher percentages of CD8+ PD-1+ T cells within the CD3 population. PD-1 blockade conferred superior antitumor efficacy in animals bearing intracranial Group 3 tumors compared to SHH group tumors, indicating that immunologic differences within the tumor microenvironment can be leveraged as potential targets to mediate antitumor efficacy. Further analysis of anti-PD-1 monoclonal antibody localization revealed binding to PD-1+ peripheral T cells, but not tumor infiltrating lymphocytes within the brain tumor microenvironment. Peripheral PD-1 blockade additionally resulted in a marked increase in CD3+ T cells within the tumor microenvironment. CONCLUSIONS This is the first immunologic characterization of preclinical models of molecular subtypes of MB and demonstration that response to immune checkpoint blockade differs across subtype classification. Our findings also suggest that effective anti-PD-1 blockade does not require that systemically administered antibodies penetrate the brain tumor microenvironment. PMID:26405194

Differential Immune Microenvironments and Response to Immune Checkpoint Blockade among Molecular Subtypes of Murine Medulloblastoma.

Science.gov (United States)

Pham, Christina D; Flores, Catherine; Yang, Changlin; Pinheiro, Elaine M; Yearley, Jennifer H; Sayour, Elias J; Pei, Yanxin; Moore, Colin; McLendon, Roger E; Huang, Jianping; Sampson, John H; Wechsler-Reya, Robert; Mitchell, Duane A

2016-02-01

Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma, the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. To address this, we adapted two syngeneic animal models of human Sonic Hedgehog (SHH)-driven and group 3 medulloblastoma for preclinical evaluation in immunocompetent C57BL/6 mice. Multicolor flow cytometric analyses were used to phenotype and characterize immune infiltrating cells within established cerebellar tumors. We observed significantly higher percentages of dendritic cells, infiltrating lymphocytes, myeloid-derived suppressor cells, and tumor-associated macrophages in murine SHH model tumors compared with group 3 tumors. However, murine group 3 tumors had higher percentages of CD8(+) PD-1(+) T cells within the CD3 population. PD-1 blockade conferred superior antitumor efficacy in animals bearing intracranial group 3 tumors compared with SHH group tumors, indicating that immunologic differences within the tumor microenvironment can be leveraged as potential targets to mediate antitumor efficacy. Further analysis of anti-PD-1 monoclonal antibody localization revealed binding to PD-1(+) peripheral T cells, but not tumor infiltrating lymphocytes within the brain tumor microenvironment. Peripheral PD-1 blockade additionally resulted in a marked increase in CD3(+) T cells within the tumor microenvironment. This is the first immunologic characterization of preclinical models of molecular subtypes of medulloblastoma and demonstration that response to immune checkpoint blockade differs across subtype classification. Our findings also suggest that effective anti-PD-1 blockade does not require that systemically administered antibodies penetrate the brain tumor microenvironment. ©2015 American Association for Cancer Research.

A Systematic Literature Review of Engineering Identity: Definitions, Factors, and Interventions Affecting Development, and Means of Measurement

Science.gov (United States)

Morelock, John R.

2017-01-01

Studies exploring what it means to be an engineer professionally have been conducted for decades, but have boomed in recent years. This systematic literature review aims to organise extant studies on engineering identity by coding around four key variables: (a) definitions of engineering identity, (b) factors affecting engineering identity…

Effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice

International Nuclear Information System (INIS)

Huston, D.P.; Smathers, P.A.; Reeves, J.P.; Steinberg, A.D.

1983-01-01

The effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice were studied. Neonatally thymectomized male and female F1 mice reconstituted with a parental or F1-irradiated thymic lobe were compared to nonreconstituted and sham-thymectomized controls. While maleness retarded the spontaneous production of ss- and ds-DNA antibodies, thymic grafts did not suppress antibodies to ss-DNA in either sex, but did suppress the production of antibodies to ds-DNA in female mice. A unique property of NZB thymic grafts was the inability to suppress anti-RBC antibodies in male mice. Thus, (i) the gender of the F1 recipient was the most important determinant of production of antibodies to ss-DNA, (ii) either maleness or the thymic microenvironment could retard production of anti-ds-DNA antibodies, and (iii) both gender and the thymic microenvironment were important in the regulation of anti-RBC antibody production. Since the administration of thymosin did not suppress autoantibody production, the effects of the thymic grafts was not solely via thymic hormone production. These studies suggest that sex hormones and/or the thymic microenvironment can exert a suppressive effect on autoantibody production and that autoantibodies differ in their susceptibility to such suppression

The effect of allometric scaling in coral thermal microenvironments.

Directory of Open Access Journals (Sweden)

Robert H Ong

Full Text Available A long-standing interest in marine science is in the degree to which environmental conditions of flow and irradiance, combined with optical, thermal and morphological characteristics of individual coral colonies, affects their sensitivity of thermal microenvironments and susceptibility to stress-induced bleaching within and/or among colonies. The physiological processes in Scleractinian corals tend to scale allometrically as a result of physical and geometric constraints on body size and shape. There is a direct relationship between scaling to thermal stress, thus, the relationship between allometric scaling and rates of heating and cooling in coral microenvironments is a subject of great interest. The primary aim of this study was to develop an approximation that predicts coral thermal microenvironments as a function of colony morphology (shape and size, light or irradiance, and flow velocity or regime. To do so, we provided intuitive interpretation of their energy budgets for both massive and branching colonies, and then quantified the heat-size exponent (b* and allometric constant (m using logarithmic linear regression. The data demonstrated a positive relationship between thermal rates and changes in irradiance, A/V ratio, and flow, with an interaction where turbulent regime had less influence on overall stress which may serve to ameliorate the effects of temperature rise compared to the laminar regime. These findings indicated that smaller corals have disproportionately higher stress, however they can reach thermal equilibrium quicker. Moreover, excellent agreements between the predicted and simulated microscale temperature values with no significant bias were observed for both the massive and branching colonies, indicating that the numerical approximation should be within the accuracy with which they could be measured. This study may assist in estimating the coral microscale temperature under known conditions of water flow and irradiance

Dysregulated pH in Tumor Microenvironment Checkmates Cancer Therapy

Directory of Open Access Journals (Sweden)

Jaleh Barar

2013-12-01

Full Text Available Introduction: The dysregulation of pH by cancerous cells of solid tumors is able to create a unique milieu that is in favor of progression, invasion and metastasis as well as chemo-/immuno-resistance traits of solid tumors. Bioelements involved in pH dysregulation provide new set of oncotargets, inhibition of which may result in better clinical outcome. Methods: To study the impacts of pH dysregulation, we investigated the tumor development and progression in relation with Warburg effect, glycolysis and formation of aberrant tumor microenvironment. Results: The upregulation of glucose transporter GLUT-1 and several enzymes involve in glycolysis exacerbates this phenomenon. The accumulation of lactic acids in cancer cells provokes upregulation of several transport machineries (MCT-1, NHE-1, CA IX and H+ pump V-ATPase resulting in reinforced efflux of proton into extracellular fluid. This deviant event makes pH to be settled at 7.4 and 6.6 respectively in cancer cells cytoplasm and extracellular fluid within the tumor microenvironment, which in return triggers secretion of lysosomal components (various enzymes in acidic milieu with pH 5 into cytoplasm. All these anomalous phenomena make tumor microenvironment (TME to be exposed to cocktail of various enzymes with acidic pH, upon which extracellular matrix (ECM can be remodeled and even deformed, resulting in emergence of a complex viscose TME with high interstitial fluid pressure. Conclusion: It seems that pH dysregulation is able to remodel various physiologic functions and make solid tumors to become much more invasive and metastatic. It also can cause undesired resistance to chemotherapy and immunotherapy. Hence, cancer therapy needs to be reinforced using specific inhibitors of bioelements involved in pH dysregulation of TME in solid tumors.

Wolsong 2, 3, and 4 quarterly progress review report on NSSS design and engineering

Energy Technology Data Exchange (ETDEWEB)

Jung, Sung Hoon; Kim, Sun Kee; Park, Tae Keun [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1995-01-01

This is the Quarterly Progress Review Report for Wolsong NPP 2, 3 and 4 NSSS Design and Engineering which evaluates the performance of the project and describes the project highlight, manpower loading status, design and engineering and project related meetings by quarterly basis. 29 figs., 16 tabs. (Author).

Hypoxia alters the physical properties of the tumor microenvironment

Science.gov (United States)

Gilkes, Daniele

Of all the deaths attributed to cancer, 90% are due to metastasis, or the spread of cancer cells from a primary tumor to distant organs, and treatments that prevent or cure metastasis remain elusive. Emerging data indicate that low oxygen states within a tumor, termed hypoxia, can alter the chemical and physical parameters of the extracellular matrix (ECM), or scaffold of the tumor tissue. These changes generate a microenvironment that may be more conducive for promoting metastasis. During tumor evolution, changes in the composition and the overall content of the ECM reflect both its biophysical and biological properties and these strongly influence the cells properties, such as cellular proliferation and cell motility. The talk will cover how hypoxia arises within normal tissue and also in tumors. We will cover the role of hypoxia in collagen biogenesis which influences compositional changes to the tumor microenvironment and discuss how these changes lead to a stiffer tumor stroma. The challenges in determining the influence of chemical versus physical cues on cancer progression will also be considered.

Internal combustion engine cold-start efficiency: A review of the problem, causes and potential solutions

International Nuclear Information System (INIS)

Roberts, Andrew; Brooks, Richard; Shipway, Philip

2014-01-01

Highlights: • The sources of I.C. engine cold start efficiency are reviewed and quantified. • Potential solutions are reviewed and the benefit quantified together. • Potential conflicts between different engine sub-systems are discussed. • Fuel consumption benefits of up to 7% are observed during cold start. • Emission reductions of up to 40% during cold start are observed. - Abstract: Legislation on vehicle emissions continues to become more stringent in an effort to minimise the impact of internal combustion engines on the environment. One area of significant concern in this respect is that of the cold-start; the thermal efficiency of the internal combustion engine is significantly lower at cold-start than when the vehicle reaches steady state temperatures owing to sub-optimal lubricant and component temperatures. The drive for thermal efficiency (of both the internal combustion engine and of the vehicle as a whole) has led to a variety of solutions being trialled to assess their merits and effects on other vehicle systems during this warm-up phase (and implemented where appropriate). The approaches have a common theme of attempting to reduce energy losses so that systems and components reach their intended operating temperature range as soon as possible after engine start. In the case of the engine, this is primarily focused on the lubricant system. Lubricant viscosity is highly sensitive to temperature and the increased viscosity at low temperatures results in higher frictional and pumping losses than would be observed at the target operating temperature. The approaches used to tackle the problem include the use of phase change materials (to reduce the cool-down rate during a period following engine running) [1,2] and the use of thermal barrier coatings in an attempt to insulate the cylinder bore and prevent heat loss (thus increasing the amount of energy utilised as brake work [3]). A range of system alterations have also been trialled including

Using Software Product Line to improve ERP Engineering: Literature Review and Analysis

Directory of Open Access Journals (Sweden)

Raúl Mazo

2014-10-01

Full Text Available On the one hand, getting advantages of Enterprise Resource Planning (ERP systems largely depends on their capacity to be configured and adapted to fit the customer and domain requirements. On the other hand, product line engineering (PLE is a promising approach for configuring and adapting products by means of configuration and derivation processes. While the literature and industrial experiences show the benefits of PLE methods, techniques and tools, there is still a lack of interest in addressing ERP engineering issues with the product line strategy. Objective: The aim of this paper is to identify and analyze the different ways presented in the literature to improve ERP engineering issues with the methods, techniques and tools provided by PLE. Method: To achieve that objective, we reviewed the literature and analyzed available publications. Results: This literature review analyzes six research papers at the intersection between ERP and PLE. It shows that the product line strategy can indeed be applied for ERP configuration and customization. It further shows the evolving interest on this topic and discusses existing contributions.

Ecotoxicity of engineered nanoparticles to aquatic invertebrates: a brief review and recommendations for future toxicity testing

DEFF Research Database (Denmark)

Baun, Anders; Hartmann, Nanna Isabella Bloch; Grieger, Khara Deanne

2008-01-01

Based on a literature review and an overview of toxic effects of engineered nanoparticles in aquatic invertebrates, this paper proposes a number of recommendations for the developing field of nanoecotoxicology by highlighting the importance of invertebrates as sensitive and relevant test organisms...... through standardized short-term (lethality) tests with invertebrates as a basis for investigating behaviour and bioavailability of engineered nanoparticles in the aquatic environment. Based on this literature review, we further recommend that research is directed towards invertebrate tests employing long....... Results show that there is a pronounced lack of data in this field (less than 20 peer-reviewed papers are published so far), and the most frequently tested engineered nanoparticles in invertebrate tests are C-60, carbon nanotubes, and titanium dioxide. In addition, the majority of the studies have used...

The Use of Motivation Theory in Engineering Education Research: A Systematic Review of Literature

Science.gov (United States)

Brown, Philip R.; McCord, Rachel E.; Matusovich, Holly M.; Kajfez, Rachel L.

2015-01-01

Motivation is frequently studied in the context of engineering education. However, the use of the term motivation can be inconsistent, both in how clearly it is defined and in how it is implemented in research designs and practice. This systematic literature review investigates the use of motivation across recent engineering education…

The senescent microenvironment promotes the emergence of heterogeneous cancer stem-like cells.

Science.gov (United States)

Castro-Vega, Luis Jaime; Jouravleva, Karina; Ortiz-Montero, Paola; Liu, Win-Yan; Galeano, Jorge Luis; Romero, Martha; Popova, Tatiana; Bacchetti, Silvia; Vernot, Jean Paul; Londoño-Vallejo, Arturo

2015-10-01

There is a well-established association between aging and the onset of metastasis. Although the mechanisms through which age impinges upon the malignant phenotype remain uncharacterized, the role of a senescent microenvironment has been emphasized. We reported previously that human epithelial cells that undergo telomere-driven chromosome instability (T-CIN) display global microRNA (miR) deregulation and develop migration and invasion capacities. Here, we show that post-crisis cells are not able to form tumors unless a senescent microenvironment is provided. The characterization of cell lines established from such tumors revealed that these cells have acquired cell autonomous tumorigenicity, giving rise to heterogeneous tumors. Further experiments demonstrate that explanted cells, while displaying differences in cell differentiation markers, are all endowed of enhanced stem cell properties including self-renewal and multilineage differentiation capacity. Treatments of T-CIN+ cells with senescence-conditioned media induce sphere formation exclusively in cells with senescence-associated tumorigenicity, a capacity that depends on miR-145 repression. These results indicate that the senescent microenvironment, while promoting further transdifferentiations in cells with genome instability, is able to propel the progression of premalignant cells towards a malignant, cell stem-like state. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Systems Engineering Leadership Development: Advancing Systems Engineering Excellence

Science.gov (United States)

Hall, Phil; Whitfield, Susan

2011-01-01

This slide presentation reviews the Systems Engineering Leadership Development Program, with particular emphasis on the work being done in the development of systems engineers at Marshall Space Flight Center. There exists a lack of individuals with systems engineering expertise, in particular those with strong leadership capabilities, to meet the needs of the Agency's exploration agenda. Therefore there is a emphasis on developing these programs to identify and train systems engineers. The presentation reviews the proposed MSFC program that includes course work, and developmental assignments. The formal developmental programs at the other centers are briefly reviewed, including the Point of Contact (POC)

Human body micro-environment: The benefits of controlling airflow interaction

DEFF Research Database (Denmark)

Melikov, Arsen Krikor

2015-01-01

This paper focuses on the micro-environment around a human body, and especially on its interaction with the surrounding environment. Research on the free convection flow generated by a human body (including the convective boundary layer around the body and the thermal plume above the body), its...

Video-rate resonant scanning multiphoton microscopy: An emerging technique for intravital imaging of the tumor microenvironment

OpenAIRE

Kirkpatrick, Nathaniel D.; Chung, Euiheon; Cook, Daniel C.; Han, Xiaoxing; Gruionu, Gabriel; Liao, Shan; Munn, Lance L.; Padera, Timothy P.; Fukumura, Dai; Jain, Rakesh K.

2012-01-01

The abnormal tumor microenvironment fuels tumor progression, metastasis, immune suppression, and treatment resistance. Over last several decades, developments in and applications of intravital microscopy have provided unprecedented insights into the dynamics of the tumor microenvironment. In particular, intravital multiphoton microscopy has revealed the abnormal structure and function of tumor-associated blood and lymphatic vessels, the role of aberrant tumor matrix in drug delivery, invasion...

Engineering - a key aspect of the UK nuclear policy review

International Nuclear Information System (INIS)

Bindon, J.L.; Butcher, Sally

1993-01-01

In anticipation of the forthcoming nuclear review, a forum on issues relevant to the industry was held at the Institution of Electrical Engineers HQ in London, in association with the Institute of Energy and the Watt Committee on Energy. The forum was divided into five sections, dealing with energy policy, the environment, industry, economics and safety. (author)

Activity pattern and personal exposure to nitrogen dioxide in indoor and outdoor microenvironments.

Science.gov (United States)

Kornartit, C; Sokhi, R S; Burton, M A; Ravindra, Khaiwal

2010-01-01

People are exposed to air pollution from a range of indoor and outdoor sources. Concentrations of nitrogen dioxide (NO(2)), which is hazardous to health, can be significant in both types of environments. This paper reports on the measurement and analysis of indoor and outdoor NO(2) concentrations and their comparison with measured personal exposure in various microenvironments during winter and summer seasons. Furthermore, the relationship between NO(2) personal exposure in various microenvironments and including activities patterns were also studied. Personal, indoor microenvironments and outdoor measurements of NO(2) levels were conducted using Palmes tubes for 60 subjects. The results showed significant differences in indoor and outdoor NO(2) concentrations in winter but not for summer. In winter, indoor NO(2) concentrations were found to be strongly correlated with personal exposure levels. NO(2) concentration in houses using a gas cooker was higher in all rooms than those with an electric cooker during the winter campaign, whereas there was no significant difference noticed in summer. The average NO(2) levels in kitchens with a gas cooker were twice as high as those with an electric cooker, with no significant difference in the summer period. A time-weighted average personal exposure was calculated and compared with measured personal exposures in various indoor microenvironments (e.g. front doors, bedroom, living room and kitchen); including non-smokers, passive smokers and smoker. The estimated results were closely correlated, but showed some underestimation of the measured personal exposures to NO(2) concentrations. Interestingly, for our particular study higher NO(2) personal exposure levels were found during summer (14.0+/-1.5) than winter (9.5+/-2.4).

Using game engine for 3D terrain visualisation of GIS data: A review

Science.gov (United States)

Che Mat, Ruzinoor; Shariff, Abdul Rashid Mohammed; Nasir Zulkifli, Abdul; Shafry Mohd Rahim, Mohd; Hafiz Mahayudin, Mohd

2014-06-01

This paper reviews on the 3D terrain visualisation of GIS data using game engines that are available in the market as well as open source. 3D terrain visualisation is a technique used to visualise terrain information from GIS data such as a digital elevation model (DEM), triangular irregular network (TIN) and contour. Much research has been conducted to transform the 2D view of map to 3D. There are several terrain visualisation softwares that are available for free, which include Cesium, Hftool and Landserf. This review paper will help interested users to better understand the current state of art in 3D terrain visualisation of GIS data using game engines.

Using game engine for 3D terrain visualisation of GIS data: A review

International Nuclear Information System (INIS)

Mat, Ruzinoor Che; Zulkifli, Abdul Nasir; Mahayudin, Mohd Hafiz; Shariff, Abdul Rashid Mohammed; Rahim, Mohd Shafry Mohd

2014-01-01

This paper reviews on the 3D terrain visualisation of GIS data using game engines that are available in the market as well as open source. 3D terrain visualisation is a technique used to visualise terrain information from GIS data such as a digital elevation model (DEM), triangular irregular network (TIN) and contour. Much research has been conducted to transform the 2D view of map to 3D. There are several terrain visualisation softwares that are available for free, which include Cesium, Hftool and Landserf. This review paper will help interested users to better understand the current state of art in 3D terrain visualisation of GIS data using game engines

Geotechnical engineering considerations in the NRC's review of uranium mill tailings remedial action plans

International Nuclear Information System (INIS)

Gillen, D.M.

1985-01-01

To reduce potential health hazards associated with inactive uranium mill tailings sites, the Department of Energy (DOE) is presently investigating and implementing remedial actions at 24 sites in the Uranium Mill Tailings Remedial Action Program (UMTRAP). All remedial actions must be selected and performed with the concurrence of the Nuclear Regulatory Commission (NRC). This paper provides a discussion of geotechnical engineering considerations during the NRC's preconcurrence review of proposed remedial action plans. In order for the NRC staff to perform an adequate geotechnical engineering review, DOE documents must contain a presentation of the properties and stability of all in-situ and engineered soil and rock which may affect the ability of the remedial action plans to meet EPA standards for long-term stability and control. Site investigations, laboratory testing, and remedial action designs must be adequate in scope and technique to provide sufficient data for the NRC staff to independently evaluate static and dynamic stability, settlement, radon attenuation through the soil cover, durability of rock for erosion protection, and other geotechnical engineering factors

Invited Review. Combustion instability in spray-guided stratified-charge engines. A review

Energy Technology Data Exchange (ETDEWEB)

Fansler, Todd D. [Univ. of Wisconsin, Madison, WI (United States); Reuss, D. L. [Univ. of Michigan, Ann Arbor, MI (United States); Sandia National Lab. (SNL-CA), Livermore, CA (United States); Sick, V. [Univ. of Michigan, Ann Arbor, MI (United States); Dahms, R. N. [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

2015-02-02

Our article reviews systematic research on combustion instabilities (principally rare, random misfires and partial burns) in spray-guided stratified-charge (SGSC) engines operated at part load with highly stratified fuel -air -residual mixtures. Results from high-speed optical imaging diagnostics and numerical simulation provide a conceptual framework and quantify the sensitivity of ignition and flame propagation to strong, cyclically varying temporal and spatial gradients in the flow field and in the fuel -air -residual distribution. For SGSC engines using multi-hole injectors, spark stretching and locally rich ignition are beneficial. Moreover, combustion instability is dominated by convective flow fluctuations that impede motion of the spark or flame kernel toward the bulk of the fuel, coupled with low flame speeds due to locally lean mixtures surrounding the kernel. In SGSC engines using outwardly opening piezo-electric injectors, ignition and early flame growth are strongly influenced by the spray's characteristic recirculation vortex. For both injection systems, the spray and the intake/compression-generated flow field influence each other. Factors underlying the benefits of multi-pulse injection are identified. Finally, some unresolved questions include (1) the extent to which piezo-SGSC misfires are caused by failure to form a flame kernel rather than by flame-kernel extinction (as in multi-hole SGSC engines); (2) the relative contributions of partially premixed flame propagation and mixing-controlled combustion under the exceptionally late-injection conditions that permit SGSC operation on E85-like fuels with very low NO_x and soot emissions; and (3) the effects of flow-field variability on later combustion, where fuel-air-residual mixing within the piston bowl becomes important.

Bone marker gene expression in calvarial bones: different bone microenvironments.

Science.gov (United States)

Al-Amer, Osama

2017-12-01

In calvarial mice, mesenchymal stem cells (MSCs) differentiate into osteoprogenitor cells and then differentiate into osteoblasts that differentiate into osteocytes, which become embedded within the bone matrix. In this case, the cells participating in bone formation include MSCs, osteoprogenitor cells, osteoblasts and osteocytes. The calvariae of C57BL/KaLwRijHsD mice consist of the following five bones: two frontal bones, two parietal bones and one interparietal bone. This study aimed to analyse some bone marker genes and bone related genes to determine whether these calvarial bones have different bone microenvironments. C57BL/KaLwRijHsD calvariae were carefully excised from five male mice that were 4-6 weeks of age. Frontal, parietal, and interparietal bones were dissected to determine the bone microenvironment in calvariae. Haematoxylin and eosin staining was used to determine the morphology of different calvarial bones under microscopy. TaqMan was used to analyse the relative expression of Runx2, OC, OSX, RANK, RANKL, OPG, N-cadherin, E-cadherin, FGF2 and FGFR1 genes in different parts of the calvariae. Histological analysis demonstrated different bone marrow (BM) areas between the different parts of the calvariae. The data show that parietal bones have the smallest BM area compared to frontal and interparietal bones. TaqMan data show a significant increase in the expression level of Runx2, OC, OSX, RANKL, OPG, FGF2 and FGFR1 genes in the parietal bones compared with the frontal and interparietal bones of calvariae. This study provides evidence that different calvarial bones, frontal, parietal and interparietal, contain different bone microenvironments.

Individual and population intake fractions of diesel particulate matter (DPM) in bus stop microenvironments

International Nuclear Information System (INIS)

Xu, Jia; Jin, Taosheng; Miao, Yaning; Han, Bin; Gao, Jiajia; Bai, Zhipeng; Xu, Xiaohong

2015-01-01

Diesel particulate matter (DPM) is associated with adverse human health effects. This study aims to investigate the relationship between DPM exposure and emissions by estimating the individual intake fraction (iF_i) and population intake fraction (iF_p) of DPM. Daily average concentrations of particulate matter at two bus stops during rush hours were measured, and then they were apportioned to DPM due to heavy-duty diesel bus emissions using Chemical Mass Balance Model. The DPM emissions of diesel buses for different driving conditions (idling, creeping and traveling) were estimated on the basis of field observations and published emission factors. The median iF_i of DPM was 0.67 and 1.39 per million for commuters standing at the bus stop and pedestrians/cyclists passing through the bus stop during rush hours, respectively. The median iF_p of DPM was 94 per million. Estimations of iF_i and iF_p of DPM are potentially significant for exposure assessment and risk management. - Highlights: • Methods to estimate the individual and population intake fraction in bus stop microenvironments were established. • Source apportionment was performed to estimate the DPM due to diesel bus emissions in bus stop microenvironments. • The DPM emission in bus stop microenvironments rather than in the entire urban area was considered. • The movement of people and their exposure duration were introduced in the estimation of population intake fraction. - This work established a method to estimate the individual and population intake fraction in transportation microenvironments on the basis of PM source apportionment.

Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

Science.gov (United States)

Riaz, Muhammad Kashif; Riaz, Muhammad Adil; Zhang, Xue; Lin, Congcong; Wong, Ka Hong; Chen, Xiaoyu; Lu, Aiping

2018-01-01

Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed. PMID:29315231

Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

Directory of Open Access Journals (Sweden)

Muhammad Kashif Riaz

2018-01-01

Full Text Available Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed.

Cell–scaffold interaction within engineered tissue

Energy Technology Data Exchange (ETDEWEB)

Chen, Haiping; Liu, Yuanyuan, E-mail: Yuanyuan_liu@shu.edu.cn; Jiang, Zhenglong; Chen, Weihua; Yu, Yongzhe; Hu, Qingxi

2014-05-01

The structure of a tissue engineering scaffold plays an important role in modulating tissue growth. A novel gelatin–chitosan (Gel–Cs) scaffold with a unique structure produced by three-dimensional printing (3DP) technology combining with vacuum freeze-drying has been developed for tissue-engineering applications. The scaffold composed of overall construction, micro-pore, surface morphology, and effective mechanical property. Such a structure meets the essential design criteria of an ideal engineered scaffold. The favorable cell–matrix interaction supports the active biocompatibility of the structure. The structure is capable of supporting cell attachment and proliferation. Cells seeded into this structure tend to maintain phenotypic shape and secreted large amounts of extracellular matrix (ECM) and the cell growth decreased the mechanical properties of scaffold. This novel biodegradable scaffold has potential applications for tissue engineering based upon its unique structure, which acts to support cell growth. - Highlights: • The scaffold is not only for providing a surface for cell residence but also for determining cell phenotype and retaining structural integrity. • The mechanical property of scaffold can be affected by activities of cell. • The scaffold provides a microenvironment for cell attachment, growth, and migration.

Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment

Energy Technology Data Exchange (ETDEWEB)

Kim, Jong-Hyuk, E-mail: jhkim@umn.edu [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Frantz, Aric M.; Anderson, Katie L.; Graef, Ashley J.; Scott, Milcah C. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Robinson, Sally [Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Sharkey, Leslie C. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); O' Brien, Timothy D. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Dickerson, Erin B. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Modiano, Jaime F., E-mail: modiano@umn.edu [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States)

2014-04-15

Interleukin-8 (IL-8) gene expression is highly up-regulated in canine hemangiosarcoma (HSA); however, its role in the pathogenesis of this disease is unknown. We investigated the expression of IL-8 in canine HSA tissues and cell lines, as well and the effects of IL-8 on canine HSA in vitro, and in vivo using a mouse xenograft model for the latter. Constitutive expression of IL-8 mRNA, IL-8 protein, and IL-8 receptor were variable among different tumor samples and cell lines, but they showed stable steady states in each cell line. Upon the addition of IL-8, HSA cells showed transient intracellular calcium fluxes, suggesting that their IL-8 receptors are functional and that IL-8 binding activates relevant signaling pathways. Yet, neither addition of exogenous IL-8 nor blockade of endogenous IL-8 by neutralizing anti-IL-8 antibody (α-IL-8 Ab) affected HSA cell proliferation or survival in vitro. To assess potential effects of IL-8 in other tumor constituents, we stratified HSA cell lines and whole tumor samples into “IL-8 high” and “IL-8 low” groups. Genome-wide gene expression profiling showed that samples in the “IL-8 high” tumor group were enriched for genes associated with a “reactive microenvironment,” including activation of coagulation, inflammation, and fibrosis networks. Based on these findings, we hypothesized that the effects of IL-8 on these tumors were mostly indirect, regulating interactions with the microenvironment. This hypothesis was supported by in vivo xenograft experiments where survival and engraftment of tumor cells was inhibited by administration of neutralizing α-IL-8 Ab. Together, our results suggest that IL-8 contributes to establishing a permissive microenvironment during the early stages of tumorigenesis in HSA. - Highlights: • IL-8 is expressed in canine hemangiosarcoma tumor samples and cell lines. • IL-8 transduces a relevant biological signal in canine hemangiosarcoma cells. • IL-8 gene signature is associated

Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment

International Nuclear Information System (INIS)

Kim, Jong-Hyuk; Frantz, Aric M.; Anderson, Katie L.; Graef, Ashley J.; Scott, Milcah C.; Robinson, Sally; Sharkey, Leslie C.; O'Brien, Timothy D.; Dickerson, Erin B.; Modiano, Jaime F.

2014-01-01

Interleukin-8 (IL-8) gene expression is highly up-regulated in canine hemangiosarcoma (HSA); however, its role in the pathogenesis of this disease is unknown. We investigated the expression of IL-8 in canine HSA tissues and cell lines, as well and the effects of IL-8 on canine HSA in vitro, and in vivo using a mouse xenograft model for the latter. Constitutive expression of IL-8 mRNA, IL-8 protein, and IL-8 receptor were variable among different tumor samples and cell lines, but they showed stable steady states in each cell line. Upon the addition of IL-8, HSA cells showed transient intracellular calcium fluxes, suggesting that their IL-8 receptors are functional and that IL-8 binding activates relevant signaling pathways. Yet, neither addition of exogenous IL-8 nor blockade of endogenous IL-8 by neutralizing anti-IL-8 antibody (α-IL-8 Ab) affected HSA cell proliferation or survival in vitro. To assess potential effects of IL-8 in other tumor constituents, we stratified HSA cell lines and whole tumor samples into “IL-8 high” and “IL-8 low” groups. Genome-wide gene expression profiling showed that samples in the “IL-8 high” tumor group were enriched for genes associated with a “reactive microenvironment,” including activation of coagulation, inflammation, and fibrosis networks. Based on these findings, we hypothesized that the effects of IL-8 on these tumors were mostly indirect, regulating interactions with the microenvironment. This hypothesis was supported by in vivo xenograft experiments where survival and engraftment of tumor cells was inhibited by administration of neutralizing α-IL-8 Ab. Together, our results suggest that IL-8 contributes to establishing a permissive microenvironment during the early stages of tumorigenesis in HSA. - Highlights: • IL-8 is expressed in canine hemangiosarcoma tumor samples and cell lines. • IL-8 transduces a relevant biological signal in canine hemangiosarcoma cells. • IL-8 gene signature is associated

Emerging nanotechnology approaches in tissue engineering for peripheral nerve regeneration.

Science.gov (United States)

Cunha, Carla; Panseri, Silvia; Antonini, Stefania

2011-02-01

Effective nerve regeneration and functional recovery subsequent to peripheral nerve injury is still a clinical challenge. Autologous nerve graft transplantation is a feasible treatment in several clinical cases, but it is limited by donor site morbidity and insufficient donor tissue, impairing complete functional recovery. Tissue engineering has introduced innovative approaches to promote and guide peripheral nerve regeneration by using biomimetic conduits creating favorable microenvironments for nervous ingrowth, but despite the development of a plethora of nerve prostheses, few approaches have as yet entered the clinic. Promising strategies using nanotechnology have recently been proposed, such as the use of scaffolds with functionalized cell-binding domains, the use of guidance channels with cell-scale internally oriented fibers, and the possibility of sustained release of neurotrophic factors. This review addresses the fabrication, advantages, drawbacks, and results achieved by the most recent nanotechnology approaches in view of future solutions for peripheral nerve repair. Peripheral nerve repair strategies are very limited despite numerous advances on the field of neurosciences and regenerative medicine. This review discusses nanotechnology based strategies including scaffolds with functionalized cell binding domains, the use of guidance channels, and the potential use of sustained release neurotropic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

Review on pressure swirl injector in liquid rocket engine

Science.gov (United States)

Kang, Zhongtao; Wang, Zhen-guo; Li, Qinglian; Cheng, Peng

2018-04-01

The pressure swirl injector with tangential inlet ports is widely used in liquid rocket engine. Commonly, this type of pressure swirl injector consists of tangential inlet ports, a swirl chamber, a converging spin chamber, and a discharge orifice. The atomization of the liquid propellants includes the formation of liquid film, primary breakup and secondary atomization. And the back pressure and temperature in the combustion chamber could have great influence on the atomization of the injector. What's more, when the combustion instability occurs, the pressure oscillation could further affects the atomization process. This paper reviewed the primary atomization and the performance of the pressure swirl injector, which include the formation of the conical liquid film, the breakup and atomization characteristics of the conical liquid film, the effects of the rocket engine environment, and the response of the injector and atomization on the pressure oscillation.

Engineering Hydrogel Microenvironments to Recapitulate the Stem Cell Niche.

Science.gov (United States)

Madl, Christopher M; Heilshorn, Sarah C

2018-06-04

Stem cells are a powerful resource for many applications including regenerative medicine, patient-specific disease modeling, and toxicology screening. However, eliciting the desired behavior from stem cells, such as expansion in a naïve state or differentiation into a particular mature lineage, remains challenging. Drawing inspiration from the native stem cell niche, hydrogel platforms have been developed to regulate stem cell fate by controlling microenvironmental parameters including matrix mechanics, degradability, cell-adhesive ligand presentation, local microstructure, and cell-cell interactions. We survey techniques for modulating hydrogel properties and review the effects of microenvironmental parameters on maintaining stemness and controlling differentiation for a variety of stem cell types. Looking forward, we envision future hydrogel designs spanning a spectrum of complexity, ranging from simple, fully defined materials for industrial expansion of stem cells to complex, biomimetic systems for organotypic cell culture models.

Inflammatory breast cancer biology: the tumour microenvironment is key.

Science.gov (United States)

Lim, Bora; Woodward, Wendy A; Wang, Xiaoping; Reuben, James M; Ueno, Naoto T

2018-04-27

Inflammatory breast cancer (IBC) is a rare and aggressive disease that accounts for ~2-4% of all breast cancers. However, despite its low incidence rate, IBC is responsible for 7-10% of breast cancer-related mortality in Western countries. Thus, the discovery of robust biological targets and the development of more effective therapeutics in IBC are crucial. Despite major international efforts to understand IBC biology, genomic studies have not led to the discovery of distinct biological mechanisms in IBC that can be translated into novel therapeutic strategies. In this Review, we discuss these molecular profiling efforts and highlight other important aspects of IBC biology. We present the intrinsic characteristics of IBC, including stemness, metastatic potential and hormone receptor positivity; the extrinsic features of the IBC tumour microenvironment (TME), including various constituent cell types; and lastly, the communication between these intrinsic and extrinsic components. We summarize the latest perspectives on the key biological features of IBC, with particular emphasis on the TME as an important contributor to the aggressive nature of IBC. On the basis of the current understanding of IBC, we hope to develop the next generation of translational studies, which will lead to much-needed survival improvements in patients with this deadly disease.

Urban air pollution in school-related microenvironments in Bogota, Colombia

Directory of Open Access Journals (Sweden)

Juan Felipe Franco

2013-05-01

Full Text Available Particle-related pollution (PM10, PM2.5 and soot was measured in both indoor and outdoor microenvironments at four public elementary schools in Bogota, Colombia. Three of these schools were located alongside major urban roads in which different types of public transit systems are used (bus rapid transit system and conventional transit buses. The fourth school was located on a non-congested road (background school. Pollutant levels at schools situated on major-roads were higher than those found at the low-congestion-road school. Outdoor black carbon daily mean concentrations at the schools located near major roads were up to six times higher than those recorded at the background school. Mean particulate matter concentrations at schools near major roads were above international standards, suggesting that school-age children in Bogota are exposed to pollution levels that are considered to be harmful by environmental and public health authorities. Elevated indoor and outdoor pollutant concentrations documented in this study suggested that traffic has a direct impact on air quality regarding the schools’ characterised microenvironments.

Automated and Adaptable Quantification of Cellular Alignment from Microscopic Images for Tissue Engineering Applications

Science.gov (United States)

Xu, Feng; Beyazoglu, Turker; Hefner, Evan; Gurkan, Umut Atakan

2011-01-01

Cellular alignment plays a critical role in functional, physical, and biological characteristics of many tissue types, such as muscle, tendon, nerve, and cornea. Current efforts toward regeneration of these tissues include replicating the cellular microenvironment by developing biomaterials that facilitate cellular alignment. To assess the functional effectiveness of the engineered microenvironments, one essential criterion is quantification of cellular alignment. Therefore, there is a need for rapid, accurate, and adaptable methodologies to quantify cellular alignment for tissue engineering applications. To address this need, we developed an automated method, binarization-based extraction of alignment score (BEAS), to determine cell orientation distribution in a wide variety of microscopic images. This method combines a sequenced application of median and band-pass filters, locally adaptive thresholding approaches and image processing techniques. Cellular alignment score is obtained by applying a robust scoring algorithm to the orientation distribution. We validated the BEAS method by comparing the results with the existing approaches reported in literature (i.e., manual, radial fast Fourier transform-radial sum, and gradient based approaches). Validation results indicated that the BEAS method resulted in statistically comparable alignment scores with the manual method (coefficient of determination R2=0.92). Therefore, the BEAS method introduced in this study could enable accurate, convenient, and adaptable evaluation of engineered tissue constructs and biomaterials in terms of cellular alignment and organization. PMID:21370940

Probing the electrostatics of active site microenvironments along the catalytic cycle for Escherichia coli dihydrofolate reductase.

Science.gov (United States)

Liu, C Tony; Layfield, Joshua P; Stewart, Robert J; French, Jarrod B; Hanoian, Philip; Asbury, John B; Hammes-Schiffer, Sharon; Benkovic, Stephen J

2014-07-23

Electrostatic interactions play an important role in enzyme catalysis by guiding ligand binding and facilitating chemical reactions. These electrostatic interactions are modulated by conformational changes occurring over the catalytic cycle. Herein, the changes in active site electrostatic microenvironments are examined for all enzyme complexes along the catalytic cycle of Escherichia coli dihydrofolate reductase (ecDHFR) by incorporation of thiocyanate probes at two site-specific locations in the active site. The electrostatics and degree of hydration of the microenvironments surrounding the probes are investigated with spectroscopic techniques and mixed quantum mechanical/molecular mechanical (QM/MM) calculations. Changes in the electrostatic microenvironments along the catalytic environment lead to different nitrile (CN) vibrational stretching frequencies and (13)C NMR chemical shifts. These environmental changes arise from protein conformational rearrangements during catalysis. The QM/MM calculations reproduce the experimentally measured vibrational frequency shifts of the thiocyanate probes across the catalyzed hydride transfer step, which spans the closed and occluded conformations of the enzyme. Analysis of the molecular dynamics trajectories provides insight into the conformational changes occurring between these two states and the resulting changes in classical electrostatics and specific hydrogen-bonding interactions. The electric fields along the CN axes of the probes are decomposed into contributions from specific residues, ligands, and solvent molecules that make up the microenvironments around the probes. Moreover, calculation of the electric field along the hydride donor-acceptor axis, along with decomposition of this field into specific contributions, indicates that the cofactor and substrate, as well as the enzyme, impose a substantial electric field that facilitates hydride transfer. Overall, experimental and theoretical data provide evidence for

ERG [Engineering Review Group] and GRG [Geologic Review Group] review of the horizontal versus vertical modes of waste emplacement at the Deaf Smith County site, Texas

International Nuclear Information System (INIS)

Chytrowski, B.R.

1988-01-01

The Engineering Review Group (ERG) and Geologic Review Group (GRG) were established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate specific issues in the US Department of Energy's nuclear waste repository program. The December 1985 meeting and the February 1986 meeting dealt with the evaluation of the Fluor Technology, Inc., architect-engineer recommendation of the horizontal mode of waste package emplacement for the Site Characterization Plan Conceptual Design Report (SCP-CDR). The ONWI recommendation regarding horizontal and vertical modes of waste package emplacement and associated studies was reviewed. This report documents the ERG and GRG's comments and recommendations on this subject and ONWI responses to the specific points raised by these groups. The ERG and GRG joint review groups concurred with ONWI recommendations that additional studies are required in order to reach a decision on the method of emplacement to be used. In the opinion of these groups, both methods can be implemented; however, should the decision be reached today the vertical mode would be preferred

Cell Factory Engineering

DEFF Research Database (Denmark)

Davy, Anne Mathilde; Kildegaard, Helene Faustrup; Andersen, Mikael Rørdam

2017-01-01

focused on individual strategies or cell types, but collectively they fall under the broad umbrella of a growing field known as cell factory engineering. Here we condense >130 reviews and key studies in the art into a meta-review of cell factory engineering. We identified 33 generic strategies......-review provides general strategy guides for the broad range of applications of rational engineering of cell factories....

Inorganic Arsenic?Related Changes in the Stromal Tumor Microenvironment in a Prostate Cancer Cell?Conditioned Media Model

OpenAIRE

Shearer, Joseph J.; Wold, Eric A.; Umbaugh, Charles S.; Lichti, Cheryl F.; Nilsson, Carol L.; Figueiredo, Marxa L.

2015-01-01

Background: The tumor microenvironment plays an important role in the progression of cancer by mediating stromal?epithelial paracrine signaling, which can aberrantly modulate cellular proliferation and tumorigenesis. Exposure to environmental toxicants, such as inorganic arsenic (iAs), has also been implicated in the progression of prostate cancer. Objective: The role of iAs exposure in stromal signaling in the tumor microenvironment has been largely unexplored. Our objective was to elucidate...

Bed Microenvironment in Hospital Patient Rooms with Natural or Mechanical Ventilation

DEFF Research Database (Denmark)

Melikov, Arsen Krikor; Li, Yuguo; Georgiev, Emanuil

2012-01-01

We studied how to provide patients in bed with thermally comfortable microenvironment in both naturally and mechanically ventilated hospital rooms for both winter and summer seasons. A climate chamber was used to resemble a hospital room and thermal manikin to simulate a patient lying in a bed...

A review of evolution of electrospun tissue engineering scaffold: From two dimensions to three dimensions.

Science.gov (United States)

Ngadiman, Nor Hasrul Akhmal; Noordin, M Y; Idris, Ani; Kurniawan, Denni

2017-07-01

The potential of electrospinning process to fabricate ultrafine fibers as building blocks for tissue engineering scaffolds is well recognized. The scaffold construct produced by electrospinning process depends on the quality of the fibers. In electrospinning, material selection and parameter setting are among many factors that contribute to the quality of the ultrafine fibers, which eventually determine the performance of the tissue engineering scaffolds. The major challenge of conventional electrospun scaffolds is the nature of electrospinning process which can only produce two-dimensional electrospun mats, hence limiting their applications. Researchers have started to focus on overcoming this limitation by combining electrospinning with other techniques to fabricate three-dimensional scaffold constructs. This article reviews various polymeric materials and their composites/blends that have been successfully electrospun for tissue engineering scaffolds, their mechanical properties, and the various parameters settings that influence the fiber morphology. This review also highlights the secondary processes to electrospinning that have been used to develop three-dimensional tissue engineering scaffolds as well as the steps undertaken to overcome electrospinning limitations.

Organic Rankine cycle - review and research directions in engine applications

Science.gov (United States)

Panesar, Angad

2017-11-01

Waste heat to power conversion using Organic Rankine Cycles (ORC) is expected to play an important role in CO2 reductions from diesel engines. Firstly, a review of automotive ORCs is presented focusing on the pure working fluids, thermal architectures and expanders. The discussion includes, but is not limited to: R245fa, ethanol and water as fluids; series, parallel and cascade as architectures; dry saturated, superheated and supercritical as expansion conditions; and scroll, radial turbine and piston as expansion machines. Secondly, research direction in versatile expander and holistic architecture (NOx + CO2) are proposed. Benefits of using the proposed unconventional approaches are quantified using Ricardo Wave and Aspen HYSYS for diesel engine and ORC modelling. Results indicate that, the implementation of versatile piston expander tolerant to two-phase and using cyclopentane can potentially increase the highway drive cycle power by 8%. Furthermore, holistic architecture offering complete utilisation of charge air and exhaust recirculation heat increased the performance noticeably to 5% of engine power at the design point condition.

A Review of Modeling Bioelectrochemical Systems: Engineering and Statistical Aspects

Directory of Open Access Journals (Sweden)

Shuai Luo

2016-02-01

Full Text Available Bioelectrochemical systems (BES are promising technologies to convert organic compounds in wastewater to electrical energy through a series of complex physical-chemical, biological and electrochemical processes. Representative BES such as microbial fuel cells (MFCs have been studied and advanced for energy recovery. Substantial experimental and modeling efforts have been made for investigating the processes involved in electricity generation toward the improvement of the BES performance for practical applications. However, there are many parameters that will potentially affect these processes, thereby making the optimization of system performance hard to be achieved. Mathematical models, including engineering models and statistical models, are powerful tools to help understand the interactions among the parameters in BES and perform optimization of BES configuration/operation. This review paper aims to introduce and discuss the recent developments of BES modeling from engineering and statistical aspects, including analysis on the model structure, description of application cases and sensitivity analysis of various parameters. It is expected to serves as a compass for integrating the engineering and statistical modeling strategies to improve model accuracy for BES development.

PAR-1 and thrombin: the ties that bind the microenvironment to melanoma metastasis.

Science.gov (United States)

Zigler, Maya; Kamiya, Takafumi; Brantley, Emily C; Villares, Gabriel J; Bar-Eli, Menashe

2011-11-01

Progression of melanoma is dependent on cross-talk between tumor cells and the adjacent microenvironment. The thrombin receptor, protease-activated receptor-1 (PAR-1), plays a key role in exerting this function during melanoma progression. PAR-1 and its activating factors, which are expressed on tumor cells and the surrounding stroma, induce not only coagulation but also cell signaling, which promotes the metastatic phenotype. Several adhesion molecules, cytokines, growth factors, and proteases have recently been identified as downstream targets of PAR-1 and have been shown to modulate interactions between tumor cells and the microenvironment in the process of melanoma growth and metastasis. Inhibiting such interactions by targeting PAR-1 could potentially be a useful therapeutic modality for melanoma patients. ©2011 AACR.

Satellite Data for All? Review of Google Earth Engine for Archaeological Remote Sensing

Directory of Open Access Journals (Sweden)

Omar A. Alcover Firpi

2016-11-01

Full Text Available A review of Google Earth Engine for archaeological remote sensing using satellite data. GEE is a freely accessible software option for processing remotely sensed data, part of the larger Google suite of products.

Effect of the Premalignant and Tumor Microenvironment on Immune Cell Cytokine Production in Head and Neck Cancer

Energy Technology Data Exchange (ETDEWEB)

Johnson, Sara D. [Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425 (United States); De Costa, Anna-Maria A. [Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, Charleston, SC 29425 (United States); Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425 (United States); Young, M. Rita I., E-mail: rita.young@va.gov [Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, Charleston, SC 29425 (United States); Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425 (United States); Medical Research Service (151), Ralph H. Johnson Veterans Affairs Medical Center, 109 Bee Street, Charleston, SC 29401 (United States)

2014-04-02

Head and neck squamous cell carcinoma (HNSCC) is marked by immunosuppression, a state in which the established tumor escapes immune attack. However, the impact of the premalignant and tumor microenvironments on immune reactivity has yet to be elucidated. The purpose of this study was to determine how soluble mediators from cells established from carcinogen-induced oral premalignant lesions and HNSCC modulate immune cell cytokine production. It was found that premalignant cells secrete significantly increased levels of G-CSF, RANTES, MCP-1, and PGE{sub 2} compared to HNSCC cells. Splenocytes incubated with premalignant supernatant secreted significantly increased levels of Th1-, Th2-, and Th17-associated cytokines compared to splenocytes incubated with HNSCC supernatant. These studies demonstrate that whereas the premalignant microenvironment elicits proinflammatory cytokine production, the tumor microenvironment is significantly less immune stimulatory and may contribute to immunosuppression in established HNSCC.

Pulmonary emphysema and tumor microenvironment in primary lung cancer.

Science.gov (United States)

Murakami, Junichi; Ueda, Kazuhiro; Sano, Fumiho; Hayashi, Masataro; Nishimoto, Arata; Hamano, Kimikazu

2016-02-01

To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer. The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD). Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05). The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

78 FR 59361 - Center for Scientific Review; Notice of Closed Meetings

Science.gov (United States)

2013-09-26

... . Name of Committee: Biological Chemistry and Macromolecular Biophysics Integrated Review Group; Synthetic and Biological Chemistry A Study Section. Date: October 21-22, 2013. Time: 8:00 a.m. to 12:00 p.m... . Name of Committee: Oncology 1-Basic Translational Integrated Review Group; Tumor Microenvironment Study...

Diesel engine exhaust gas recirculation--a review on advanced and novel concepts

Energy Technology Data Exchange (ETDEWEB)

Zheng Ming E-mail: mzheng@uwindsor.ca; Reader, Graham T.; Hawley, J. Gary

2004-04-01

Exhaust gas recirculation (EGR) is effective to reduce nitrogen oxides (NO{sub x}) from Diesel engines because it lowers the flame temperature and the oxygen concentration of the working fluid in the combustion chamber. However, as NO{sub x} reduces, particulate matter (PM) increases, resulting from the lowered oxygen concentration. When EGR further increases, the engine operation reaches zones with higher instabilities, increased carbonaceous emissions and even power losses. In this research, the paths and limits to reduce NO{sub x} emissions from Diesel engines are briefly reviewed, and the inevitable uses of EGR are highlighted. The impact of EGR on Diesel operations is analyzed and a variety of ways to implement EGR are outlined. Thereafter, new concepts regarding EGR stream treatment and EGR hydrogen reforming are proposed.

A review on chitosan centred scaffolds and their applications in tissue engineering.

Science.gov (United States)

Ahmed, Shakeel; Annu; Sheikh, Javed; Ali, Akbar

2018-05-03

The diversity and availability of biopolymer and increased clinical demand for safe scaffolds lead to an increased interest in fabricating scaffolds in order to achieve fruitful progress in tissue engineering. Due to biocompatibility, biodegradability, inherent antimicrobial character, chitosan has drawn ample consideration in recent years. Chitosan is a biopolymer obtained by de-acetylation of chitin extracted from shells of crustaceans and fungi. Due to the presence of reactive functionality in the molecular chain chitosan can be modified either chemically or physically to fabricate the tailor-made scaffolds having desired properties for tissue engineering centered applications. In this review chitosan, its properties and role either virgin, chemically or physically modified, 2D or 3D scaffolds for tissue engineering application have been highlighted. Copyright © 2017. Published by Elsevier B.V.

SPHINGOSINE-1 PHOSPHATE: A NEW MODULATOR OF IMMUNE PLASTICITY IN THE TUMOR MICROENVIRONMENT

Directory of Open Access Journals (Sweden)

Yamila I Rodriguez

2016-10-01

Full Text Available In the last 15 years, increasing evidences demonstrate a strong link between sphingosine-1-phosphate (S1P in both normal physiology and progression of different diseases, including cancer and inflammation. Indeed, numerous studies show that tissue levels of this sphingolipid metabolite are augmented in many cancers, affecting survival, proliferation, angiogenesis and metastatic spread. Recent insights into the possible role of S1P as a therapeutic target has attracted enormous attention and opened new opportunities in this evolving field. In this review we will focus on the role of S1P in cancer with particular emphasis in new developments that highlight the many functions of this sphingolipid in the tumor microenvironment. We will discuss how S1P modulates phenotypic plasticity of macrophages and mast cells, tumor-induced immune evasion, differentiation and survival of immune cells in the tumor milieu, interaction between cancer and stromal cells and hypoxic response.

Quantifying the mechanical micro-environment during three-dimensional cell expansion on microbeads by means of individual cell-based modelling.

Science.gov (United States)

Smeets, Bart; Odenthal, Tim; Tijskens, Engelbert; Ramon, Herman; Van Oosterwyck, Hans

2013-10-01

Controlled in vitro three-dimensional cell expansion requires culture conditions that optimise the biophysical micro-environment of the cells during proliferation. In this study, we propose an individual cell-based modelling platform for simulating the mechanics of cell expansion on microcarriers. The lattice-free, particle-based method considers cells as individual interacting particles that deform and move over time. The model quantifies how the mechanical micro-environment of individual cells changes during the time of confluency. A sensitivity analysis is performed, which shows that changes in the cell-specific properties of cell-cell adhesion and cell stiffness cause the strongest change in the mechanical micro-environment of the cells. Furthermore, the influence of the mechanical properties of cells and microbead is characterised. The mechanical micro-environment is strongly influenced by the adhesive properties and the size of the microbead. Simulations show that even in the absence of strong biological heterogeneity, a large heterogeneity in mechanical stresses can be expected purely due to geometric properties of the culture system.

Human β-defensin 3-combined gold nanoparticles for enhancement of osteogenic differentiation of human periodontal ligament cells in inflammatory microenvironments

Directory of Open Access Journals (Sweden)

Zhou J

2018-01-01

Full Text Available Jing Zhou,1 Yangheng Zhang,1 Lingjun Li,1 Huangmei Fu,2 Wenrong Yang,2 Fuhua Yan1 1Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2School of Life and Environmental Science, Centre for Chemistry and Biotechnology, Deakin University, Geelong, VIC, Australia Objective: It is a great challenge to absorb and conduct biophysicochemical interactions at the nano-bio interface. Peptides are emerging as versatile materials whose function can be programmed to perform specific tasks. Peptides combined nanoparticles might be utilized as a new approach of treatment. Human β-defensin 3 (hBD3, possesses both antimicrobial and proregeneration properties. Gold nanoparticles (AuNPs have shown promising applications in the field of tissue engineering. However, the coordinating effects of AuNPs and hBD3 on human periodontal ligament cells (hPDLCs remain unknown. In this study, we systematically investigated whether AuNPs and hBD3 would be able to coordinate and enhance the osteogenic differentiation of hPDLCs in inflammatory microenvironments, and the underlying mechanisms was explored. Methods: hPDLCs were stimulated with E. coli-LPS, hBD3 and AuNPs. Alkaline phosphatase (ALP and alizarin red S staining were used to observe the effects of hBD3 and AuNPs on the osteogenic differentiation of hPDLCs. Real-time PCR and western blot were performed to evaluate the osteogenic differentiation and Wnt/β-catenin signaling pathway related gene and protein expression.Results: In the inflammatory microenvironments stimulated by E. coli-LPS, we found that AuNPs and hBD3 increased the proliferation of hPDLCs slightly. In addition, hBD3-combined AuNPs could significantly enhance ALP activities and mineral deposition in vitro. Meanwhile, we observed that the osteogenic differentiation-related gene and protein expressions of ALP, collagenase-I (COL-1 and runt-related transcription factor 2 (Runx-2 were

Carbonic anhydrase IX (CA IX) mediates tumor cell interactions with microenvironment

Czech Academy of Sciences Publication Activity Database

Závadová, Zuzana; Závada, Jan

2005-01-01

Roč. 13, č. 5 (2005), s. 977-982 ISSN 1021-335X R&D Projects: GA ČR(CZ) GA203/02/0405 Institutional research plan: CEZ:AV0Z50520514 Keywords : carbonic anhydrase IX * cell adhesion * microenvironment Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.572, year: 2005

Tumor Microenvironment Modulation via Gold Nanoparticles Targeting Malicious Exosomes: Implications for Cancer Diagnostics and Therapy

Directory of Open Access Journals (Sweden)

Catarina Roma-Rodrigues

2017-01-01

Full Text Available Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes’ release and/or uptake to inhibit or delay tumor development. In recent years, nanotechnology has paved the way for the development of a plethora of new diagnostic and therapeutic platforms, fostering theranostics. The unique physical and chemical properties of gold nanoparticles (AuNPs make them suitable vehicles to pursuit this goal. AuNPs’ properties such as ease of synthesis with the desired shape and size, high surface:volume ratio, and the possibility of engineering their surface as desired, potentiate AuNPs’ role in nanotheranostics, allowing the use of the same formulation for exosome detection and restraining the effect of malicious exosomes in cancer progression.

Tumor Microenvironment Modulation via Gold Nanoparticles Targeting Malicious Exosomes: Implications for Cancer Diagnostics and Therapy.

Science.gov (United States)

Roma-Rodrigues, Catarina; Raposo, Luís R; Cabral, Rita; Paradinha, Fabiana; Baptista, Pedro V; Fernandes, Alexandra R

2017-01-14

Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes' release and/or uptake to inhibit or delay tumor development. In recent years, nanotechnology has paved the way for the development of a plethora of new diagnostic and therapeutic platforms, fostering theranostics. The unique physical and chemical properties of gold nanoparticles (AuNPs) make them suitable vehicles to pursuit this goal. AuNPs' properties such as ease of synthesis with the desired shape and size, high surface:volume ratio, and the possibility of engineering their surface as desired, potentiate AuNPs' role in nanotheranostics, allowing the use of the same formulation for exosome detection and restraining the effect of malicious exosomes in cancer progression.

Mini-review: In vitro Metabolic Engineering for Biomanufacturing of High-value Products

Directory of Open Access Journals (Sweden)

Weihua Guo

Full Text Available With the breakthroughs in biomolecular engineering and synthetic biology, many valuable biologically active compound and commodity chemicals have been successfully manufactured using cell-based approaches in the past decade. However, because of the high complexity of cell metabolism, the identification and optimization of rate-limiting metabolic pathways for improving the product yield is often difficult, which represents a significant and unavoidable barrier of traditional in vivo metabolic engineering. Recently, some in vitro engineering approaches were proposed as alternative strategies to solve this problem. In brief, by reconstituting a biosynthetic pathway in a cell-free environment with the supplement of cofactors and substrates, the performance of each biosynthetic pathway could be evaluated and optimized systematically. Several value-added products, including chemicals, nutraceuticals, and drug precursors, have been biosynthesized as proof-of-concept demonstrations of in vitro metabolic engineering. This mini-review summarizes the recent progresses on the emerging topic of in vitro metabolic engineering and comments on the potential application of cell-free technology to speed up the “design-build-test” cycles of biomanufacturing. Keywords: Cell-free, Biosynthesis, Metabolic pathways, Design-build-test cycle

The Nuclear Review: the Institution of Nuclear Engineers' response to the Review of Nuclear Power

International Nuclear Information System (INIS)

Anon.

1994-01-01

The United Kingdom Government's Nuclear Review currently underway, addresses whether and in what form nuclear power should continue to be part of the country's power generation capability. This article sets out the response of the Institution of Nuclear Engineers to the Nuclear Review. This pro-nuclear group emphasises the benefits to be gained from diversity of generation in the energy supply industry. The environmentally benign nature of nuclear power is emphasised, in terms of gaseous emissions. The industry's excellent safety record also argues in favour of nuclear power. Finally, as power demand increases globally, a health U.K. nuclear industry could generate British wealth through power exports and via the construction industry. The Institution's view on radioactive waste management is also set out. (UK)

Alkaline biodegradable implants for osteoporotic bone defects--importance of microenvironment pH.

Science.gov (United States)

Liu, W; Wang, T; Yang, C; Darvell, B W; Wu, J; Lin, K; Chang, J; Pan, H; Lu, W W

2016-01-01

Change of microenvironment pH by biodegradable implants may ameliorate unbalanced osteoporotic bone remodeling. The present work demonstrated that a weak alkaline condition stimulated osteoblasts differentiation while suppressed osteoclast generation. In vivo, implants with an alkaline microenvironment pH (monitored by a pH microelectrode) exhibited a promising healing effect for the repair of osteoporotic bone defects. Under osteoporotic conditions, the response of the bone microenvironment to an endosseous implant is significantly impaired, and this substantially increases the risk of fracture, non-union and aseptic implant loosening. Acid-base equilibrium is an important factor influencing bone cell behaviour. The present purpose was to study the effect of a series of alkaline biodegradable implant materials on regeneration of osteoporotic bone defect, monitoring the microenvironment pH (μe-pH) over time. The proliferation and differentiation potential of osteoporotic rat bone marrow stromal cells and RAW 264.7 cells were examined under various pH conditions. Ovariectomized rat bone defects were filled with specific biodegradable materials, and μe-pH was measured by pH microelectrode. New osteoid and tartrate-resistant acid phosphatase-positive osteoclast-like cells were examined by Goldner's trichrome and TRAP staining, respectively. The intermediate layer between implants and new bone were studied using energy-dispersive X-ray spectroscopy (EDX) linear scanning. In vitro, weak alkaline conditions stimulated osteoporotic rat bone marrow stromal cells (oBMSC) differentiation, while inhibiting the formation of osteoclasts. In vivo, μe-pH differs from that of the homogeneous peripheral blood and exhibits variations over time particular to each material. Higher initial μe-pH was associated with more new bone formation, late response of TRAP-positive osteoclast-like cells and the development of an intermediate 'apatitic' layer in vivo. EDX suggested that

NRC Reviewer Aid for Evaluating the Human Factors Engineering Aspects of Small Modular Reactors

International Nuclear Information System (INIS)

OHara, J.M.; Higgins, J.C.

2012-01-01

Small modular reactors (SMRs) are a promising approach to meeting future energy needs. Although the electrical output of an individual SMR is relatively small compared to that of typical commercial nuclear plants, they can be grouped to produce as much energy as a utility demands. Furthermore, SMRs can be used for other purposes, such as producing hydrogen and generating process heat. The design characteristics of many SMRs differ from those of current conventional plants and may require a distinct concept of operations (ConOps). The U.S. Nuclear Regulatory Commission (NRC) conducted research to examine the human factors engineering (HFE) and the operational aspects of SMRs. The research identified thirty potential human-performance issues that should be considered in the NRC's reviews of SMR designs and in future research activities. The purpose of this report is to support NRC HFE reviewers of SMR applications by identifying some of the questions that can be asked of applicants whose designs have characteristics identified in the issues. The questions for each issue were identified and organized based on the review elements and guidance contained in Chapter 18 of the Standard Review Plan (NUREG-0800), and the Human Factors Engineering Program Review Model (NUREG-0711).

Glycogen metabolism has a key role in the cancer microenvironment and provides new targets for cancer therapy.

Science.gov (United States)

Zois, Christos E; Harris, Adrian L

2016-02-01

Metabolic reprogramming is a hallmark of cancer cells and contributes to their adaption within the tumour microenvironment and resistance to anticancer therapies. Recently, glycogen metabolism has become a recognised feature of cancer cells since it is upregulated in many tumour types, suggesting that it is an important aspect of cancer cell pathophysiology. Here, we provide an overview of glycogen metabolism and its regulation, with a focus on its role in metabolic reprogramming of cancer cells under stress conditions such as hypoxia, glucose deprivation and anticancer treatment. The various methods to detect glycogen in tumours in vivo as well as pharmacological modulators of glycogen metabolism are also reviewed. Finally, we discuss the therapeutic value of targeting glycogen metabolism as a strategy for combinational approaches in cancer treatment.

Evaluation of daily time spent in transportation and traffic-influenced microenvironments by urban Canadians.

Science.gov (United States)

Matz, Carlyn J; Stieb, David M; Egyed, Marika; Brion, Orly; Johnson, Markey

2018-01-01

Exposure to traffic and traffic-related air pollution is associated with a wide array of health effects. Time spent in a vehicle, in active transportation, along roadsides, and in close proximity to traffic can substantially contribute to daily exposure to air pollutants. For this study, we evaluated daily time spent in transportation and traffic-influenced microenvironments by urban Canadians using the Canadian Human Activity Pattern Survey (CHAPS) 2 results. Approximately 4-7% of daily time was spent in on- or near-road locations, mainly associated with being in a vehicle and smaller contributions from active transportation. Indoor microenvironments can be impacted by traffic emissions, especially when located near major roadways. Over 60% of the target population reported living within one block of a roadway with moderate to heavy traffic, which was variable with income level and city, and confirmed based on elevated NO 2 exposure estimated using land use regression. Furthermore, over 55% of the target population ≤ 18 years reported attending a school or daycare in close proximity to moderate to heavy traffic, and little variation was observed based on income or city. The results underline the importance of traffic emissions as a major source of exposure in Canadian urban centers, given the time spent in traffic-influenced microenvironments.

Age-related inflammatory bone marrow microenvironment induces ineffective erythropoiesis mimicking del(5q) MDS.

Science.gov (United States)

Mei, Y; Zhao, B; Basiorka, A A; Yang, J; Cao, L; Zhang, J; List, A; Ji, P

2018-04-01

Anemia is characteristic of myelodysplastic syndromes (MDS). The mechanisms of anemia in MDS are unclear. Using a mouse genetic approach, here we show that dual deficiency of mDia1 and miR-146a, encoded on chromosome 5q and commonly deleted in MDS (del(5q) MDS), causes an age-related anemia and ineffective erythropoiesis mimicking human MDS. We demonstrate that the ageing bone marrow microenvironment is important for the development of ineffective erythropoiesis in these mice. Damage-associated molecular pattern molecules (DAMPs), whose levels increase in ageing bone marrow, induced TNFα and IL-6 upregulation in myeloid-derived suppressor cells (MDSCs) in mDia1/miR-146a double knockout mice. Mechanistically, we reveal that pathologic levels of TNFα and IL-6 inhibit erythroid colony formation and differentially affect terminal erythropoiesis through reactive oxygen species-induced caspase-3 activation and apoptosis. Treatment of the mDia1/miR-146a double knockout mice with all-trans retinoic acid, which promoted the differentiation of MDSCs and ameliorated the inflammatory bone marrow microenvironment, significantly rescued anemia and ineffective erythropoiesis. Our study underscores the dual roles of the ageing microenvironment and genetic abnormalities in the pathogenesis of ineffective erythropoiesis in del(5q) MDS.

Catalog of gene expression in adult neural stem cells and their in vivo microenvironment

International Nuclear Information System (INIS)

Williams, Cecilia; Wirta, Valtteri; Meletis, Konstantinos; Wikstroem, Lilian; Carlsson, Leif; Frisen, Jonas; Lundeberg, Joakim

2006-01-01

Stem cells generally reside in a stem cell microenvironment, where cues for self-renewal and differentiation are present. However, the genetic program underlying stem cell proliferation and multipotency is poorly understood. Transcriptome analysis of stem cells and their in vivo microenvironment is one way of uncovering the unique stemness properties and provides a framework for the elucidation of stem cell function. Here, we characterize the gene expression profile of the in vivo neural stem cell microenvironment in the lateral ventricle wall of adult mouse brain and of in vitro proliferating neural stem cells. We have also analyzed an Lhx2-expressing hematopoietic-stem-cell-like cell line in order to define the transcriptome of a well-characterized and pure cell population with stem cell characteristics. We report the generation, assembly and annotation of 50,792 high-quality 5'-end expressed sequence tag sequences. We further describe a shared expression of 1065 transcripts by all three stem cell libraries and a large overlap with previously published gene expression signatures for neural stem/progenitor cells and other multipotent stem cells. The sequences and cDNA clones obtained within this framework provide a comprehensive resource for the analysis of genes in adult stem cells that can accelerate future stem cell research

Role of plant biotechnology and genetic engineering in crop-improvement, with special emphases on cotton: A review

International Nuclear Information System (INIS)

Akhtar, L.H.; Siddiq, S.Z.; Tariq, A.H.; Arshad, M.; Gorham, J.

2003-01-01

Plant biotechnology and genetic engineering offer novel approaches to plant-breeding, production, propagation and preservation of germplasm. In this manuscript, the population and food-requirements of Pakistan, role of biotechnology and genetic engineering in crop-improvement, along with potential uses in cotton, have been discussed. The latest position of plant biotechnology and genetic engineering in Pakistan and the advantages of biotechnology and genetic-engineering techniques over conventional plant-breeding techniques, along with critical views of various scientists have been reviewed. (author)

ATP/P2X7 axis modulates myeloid-derived suppressor cell functions in neuroblastoma microenvironment.

Science.gov (United States)

Bianchi, G; Vuerich, M; Pellegatti, P; Marimpietri, D; Emionite, L; Marigo, I; Bronte, V; Di Virgilio, F; Pistoia, V; Raffaghello, L

2014-03-20

Tumor microenvironment of solid tumors is characterized by a strikingly high concentration of adenosine and ATP. Physiological significance of this biochemical feature is unknown, but it has been suggested that it may affect infiltrating immune cell responses and tumor progression. There is increasing awareness that many of the effects of extracellular ATP on tumor and inflammatory cells are mediated by the P2X7 receptor (P2X7R). Aim of this study was to investigate whether: (i) extracellular ATP is a component of neuroblastoma (NB) microenvironment, (ii) myeloid-derived suppressor cells (MDSCs) express functional P2X7R and (iii) the ATP/P2X7R axis modulates MDSC functions. Our results show that extracellular ATP was detected in NB microenvironment in amounts that increased in parallel with tumor progression. The percentage of CD11b(+)/Gr-1(+) cells was higher in NB-bearing mice compared with healthy animals. Within the CD11b/Gr-1(+) population, monocytic MDSCs (M-MDSCs) produced higher levels of reactive oxygen species (ROS), arginase-1 (ARG-1), transforming growth factor-β1 (TGF-β1) and stimulated more potently in vivo tumor growth, as compared with granulocytic MDSCs (G-MDSCs). P2X7R of M-MDSCs was localized at the plasma membrane, coupled to increased functionality, upregulation of ARG-1, TGF-β1 and ROS. Quite surprisingly, the P2X7R in primary MDSCs as well as in the MSC-1 and MSC-2 lines was uncoupled from cytotoxicity. This study describes a novel scenario in which MDSC immunosuppressive functions are modulated by the ATP-enriched tumor microenvironment.

Hyaluronan - a functional and structural sweet spot in the tissue microenvironment

Directory of Open Access Journals (Sweden)

James eMonslow

2015-05-01

Full Text Available Transition from homeostatic to reactive matrix remodeling is a fundamental adaptive tissue response to injury, inflammatory disease, fibrosis and cancer. Alterations in architecture, physical properties and matrix composition result in changes in biomechanical and biochemical cellular signaling. The dynamics of pericellular and extracellular matrices, including matrix protein, proteoglycan and glycosaminoglycan modification are continually emerging as essential regulatory mechanisms underlying cellular and tissue function. Nevertheless, the impact of matrix organization on inflammation and immunity in particular, and the consequent effects on tissue healing and disease outcome are arguably under-studied aspects of adaptive stress responses. Herein, we review how the predominant glycosaminoglycan hyaluronan (HA contributes to the structure and function of the tissue microenvironment. Specifically, we examine the evidence of HA degradation and the generation of biologically-active smaller HA fragments in pathological settings in vivo. We discuss how HA fragments versus nascent HA via alternate receptor-mediated signaling influence inflammatory cell recruitment and differentiation, resident cell activation, as well as tumor growth, survival and metastasis. Finally, we discuss how HA fragmentation impacts restoration of normal tissue function and pathological outcomes in disease.

Tissue engineering strategies for alveolar cleft reconstruction: a systematic review of the literature

NARCIS (Netherlands)

Janssen, N.G.; Weijs, W.L.J.; Koole, R.A.; Rosenberg, A.J.; Meijer, G.J.

2014-01-01

OBJECTIVES: To date, a great number of tissue engineering strategies have been suggested for alveolar cleft reconstruction; however, autologous bone grafting seems to remain the golden standard. MATERIALS AND METHODS: A systematic review of the literature was conducted in order to evaluate the

Using Peer Reviews to Examine Micropolitics and Disciplinary Development of Engineering Education: A Case Study

Science.gov (United States)

Beddoes, Kacey

2014-01-01

This article presents a case study of the peer review process for a feminist article submitted to an engineering education journal. It demonstrates how an examination of peer review can be a useful approach to further understanding the development of feminist thought in education fields. Rather than opposition to feminist thought per se, my…

Review of spectral imaging technology in biomedical engineering: achievements and challenges.

Science.gov (United States)

Li, Qingli; He, Xiaofu; Wang, Yiting; Liu, Hongying; Xu, Dongrong; Guo, Fangmin

2013-10-01

Spectral imaging is a technology that integrates conventional imaging and spectroscopy to get both spatial and spectral information from an object. Although this technology was originally developed for remote sensing, it has been extended to the biomedical engineering field as a powerful analytical tool for biological and biomedical research. This review introduces the basics of spectral imaging, imaging methods, current equipment, and recent advances in biomedical applications. The performance and analytical capabilities of spectral imaging systems for biological and biomedical imaging are discussed. In particular, the current achievements and limitations of this technology in biomedical engineering are presented. The benefits and development trends of biomedical spectral imaging are highlighted to provide the reader with an insight into the current technological advances and its potential for biomedical research.

3D printed porous ceramic scaffolds for bone tissue engineering: a review.

Science.gov (United States)

Wen, Yu; Xun, Sun; Haoye, Meng; Baichuan, Sun; Peng, Chen; Xuejian, Liu; Kaihong, Zhang; Xuan, Yang; Jiang, Peng; Shibi, Lu

2017-08-22

This study summarizes the recent research status and development of three-dimensional (3D)-printed porous ceramic scaffolds in bone tissue engineering. Recent literature on 3D-printed porous ceramic scaffolds was reviewed. Compared with traditional processing and manufacturing technologies, 3D-printed porous ceramic scaffolds have obvious advantages, such as enhancement of the controllability of the structure or improvement of the production efficiency. More sophisticated scaffolds were fabricated by 3D printing technology. 3D printed bioceramics have broad application prospects in bone tissue engineering. Through understanding the advantages and limitations of different 3D-printing approaches, new classes of bone graft substitutes can be developed.

Personal exposure monitoring of PM2.5 in indoor and outdoor microenvironments

DEFF Research Database (Denmark)

Steinle, Susanne; Reis, Stefan; Sabel, Clive E

2015-01-01

to define six microenvironments (MEs) to assess everyday exposure of individuals to short-term PM2.5 concentrations. The Dylos was combined with a GPS receiver to track movement and exposure of individuals across the MEs. Seventeen volunteers collected 35 profiles. Profiles may have a different overall...

Smart blood cell and microvesicle-based Trojan horse drug delivery: Merging expertise in blood transfusion and biomedical engineering in the field of nanomedicine.

Science.gov (United States)

Wu, Yu-Wen; Goubran, Hadi; Seghatchian, Jerard; Burnouf, Thierry

2016-04-01

Therapeutic and diagnostic applications of nanomedicine are playing increasingly important roles in human health. Various types of synthetic nanoparticles, including liposomes, micelles, and other nanotherapeutic platforms and conjugates, are being engineered to encapsulate or carry drugs for treating diseases such as cancer, cardiovascular disorders, neurodegeneration, and inflammations. Nanocarriers are designed to increase the half-life of drugs, decrease their toxicity and, ideally, target pathological sites. Developing smart carriers with the capacity to deliver drugs specifically to the microenvironment of diseased cells with minimum systemic toxicity is the goal. Blood cells, and potentially also the liposome-like micro- and nano-vesicles they generate, may be regarded as ideally suited to perform such specific targeting with minimum immunogenic risks. Blood cell membranes are "decorated" with complex physiological receptors capable of targeting and communicating with other cells and tissues and delivering their content to the surrounding pathological microenvironment. Blood cells, such as erythrocytes, have been developed as permeable carriers to release drugs to diseased tissues or act as biofactory allowing enzymatic degradation of a pathological substrate. Interestingly, attempts are also being made to improve the targeting capacity of synthetic nanoparticles by "decorating" their surface with blood cell membrane receptor-like biochemical structures. Research is needed to further explore the benefits that blood cell-derived microvesicles, as a Trojan horse delivery systems, can bring to the arsenal of therapeutic micro- and nanotechnologies. This short review focuses on the therapeutic roles that red blood cells and platelets can play as smart drug-delivery systems, and highlights the benefits that blood transfusion expertise can bring to this exciting and novel biomedical engineering field. Copyright © 2016 Elsevier Ltd. All rights reserved.

2015 Space Human Factors Engineering Standing Review Panel

Science.gov (United States)

Steinberg, Susan

2015-01-01

The 2015 Space Human Factors Engineering (SHFE) Standing Review Panel (from here on referred to as the SRP) met for a site visit in Houston, TX on December 2 - 3, 2015. The SRP reviewed the updated research plans for the Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI Risk), the Risk of Inadequate Human-Computer Interaction (HCI Risk), and the Risk of Inadequate Mission, Process and Task Design (MPTask Risk). The SRP also received a status update on the Risk of Incompatible Vehicle/Habitat Design (Hab Risk) and the Risk of Performance Errors Due to Training Deficiencies (Train Risk). The SRP is pleased with the progress and responsiveness of the SHFE team. The presentations were much improved this year. The SRP is also pleased with the human-centered design approach. Below are some of the more extensive comments from the SRP. We have also made comments in each section concerning gaps/tasks in each. The comments below reflect more significant changes that impact more than just one particular section.

Nocardia brasiliensis induces an immunosuppressive microenvironment that favors chronic infection in BALB/c mice.

Science.gov (United States)

Rosas-Taraco, Adrian G; Perez-Liñan, Amira R; Bocanegra-Ibarias, Paola; Perez-Rivera, Luz I; Salinas-Carmona, Mario C

2012-07-01

Nocardia brasiliensis is an intracellular microorganism and the most common etiologic agent of actinomycetoma in the Americas. Several intracellular pathogens induce an immunosuppressive microenvironment through increases in CD4+ Foxp3+ regulatory T cells (Treg), thus downregulating other T-cell subpopulations and assuring survival in the host. In this study, we determined whether N. brasiliensis modulates T-lymphocyte responses and their related cytokine profiles in a murine experimental model. We also examined the relationship between N. brasiliensis immunomodulation and pathogenesis and bacterial survival. In early infection, Th17/Tc17 cells were increased at day 3 (P 1 log) was also observed (P brasiliensis modulates the immune system to induce an immunosuppressive microenvironment that benefits its survival during the chronic stage of infection.

Effect of engine parameters and type of gaseous fuel on the performance of dual-fuel gas diesel engines. A critical review

Energy Technology Data Exchange (ETDEWEB)

Sahoo, B.B. [Centre for Energy, Indian Institute of Technology, Guwahati 781039 (India); Sahoo, N.; Saha, U.K. [Department of Mechanical Engineering, Indian Institute of Technology, Guwahati 781039 (India)

2009-08-15

Petroleum resources are finite and, therefore, search for their alternative non-petroleum fuels for internal combustion engines is continuing all over the world. Moreover gases emitted by petroleum fuel driven vehicles have an adverse effect on the environment and human health. There is universal acceptance of the need to reduce such emissions. Towards this, scientists have proposed various solutions for diesel engines, one of which is the use of gaseous fuels as a supplement for liquid diesel fuel. These engines, which use conventional diesel fuel and gaseous fuel, are referred to as 'dual-fuel engines'. Natural gas and bio-derived gas appear more attractive alternative fuels for dual-fuel engines in view of their friendly environmental nature. In the gas-fumigated dual-fuel engine, the primary fuel is mixed outside the cylinder before it is inducted into the cylinder. A pilot quantity of liquid fuel is injected towards the end of the compression stroke to initiate combustion. When considering a gaseous fuel for use in existing diesel engines, a number of issues which include, the effects of engine operating and design parameters, and type of gaseous fuel, on the performance of the dual-fuel engines, are important. This paper reviews the research on above issues carried out by various scientists in different diesel engines. This paper touches upon performance, combustion and emission characteristics of dual-fuel engines which use natural gas, biogas, producer gas, methane, liquefied petroleum gas, propane, etc. as gaseous fuel. It reveals that 'dual-fuel concept' is a promising technique for controlling both NO{sub x} and soot emissions even on existing diesel engine. But, HC, CO emissions and 'bsfc' are higher for part load gas diesel engine operations. Thermal efficiency of dual-fuel engines improve either with increased engine speed, or with advanced injection timings, or with increased amount of pilot fuel. The ignition

Women of Color in Mathematics, Science & Engineering: A Review of the Literature.

Science.gov (United States)

Clewell, Beatriz Chu; Anderson, Bernice

This review of the literature on women of color in mathematics, science, and engineering helps define the need for a national agenda for equity in these fields sponsored by the Educational Equity Policy Studies Program of the Center for Women Policy Studies, and for a comprehensive research program that examines barriers to the participation of…

A review of fibrin and fibrin composites for bone tissue engineering.

Science.gov (United States)

Noori, Alireza; Ashrafi, Seyed Jamal; Vaez-Ghaemi, Roza; Hatamian-Zaremi, Ashraf; Webster, Thomas J

2017-01-01

Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient's own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the

Review of vascularised bone tissue-engineering strategies with a focus on co-culture systems.

Science.gov (United States)

Liu, Yuchun; Chan, Jerry K Y; Teoh, Swee-Hin

2015-02-01

Poor angiogenesis within tissue-engineered grafts has been identified as a main challenge limiting the clinical introduction of bone tissue-engineering (BTE) approaches for the repair of large bone defects. Thick BTE grafts often exhibit poor cellular viability particularly at the core, leading to graft failure and lack of integration with host tissues. Various BTE approaches have been explored for improving vascularisation in tissue-engineered constructs and are briefly discussed in this review. Recent investigations relating to co-culture systems of endothelial and osteoblast-like cells have shown evidence of BTE efficacy in increasing vascularization in thick constructs. This review provides an overview of key concepts related to bone formation and then focuses on the current state of engineered vascularized co-culture systems using bone repair as a model. It will also address key questions regarding the generation of clinically relevant vascularized bone constructs as well as potential directions and considerations for research with the objective of pursuing engineered co-culture systems in other disciplines of vascularized regenerative medicine. The final objective is to generate serious and functional long-lasting vessels for sustainable angiogenesis that will enable enhanced cellular survival within thick voluminous bone grafts, thereby aiding in bone formation and remodelling in the long term. However, more evidence about the quality of blood vessels formed and its associated functional improvement in bone formation as well as a mechanistic understanding of their interactions are necessary for designing better therapeutic strategies for translation to clinical settings. Copyright © 2012 John Wiley & Sons, Ltd.

Sensitivity of Dendritic Cells to Microenvironment Signals

Directory of Open Access Journals (Sweden)

Juliana Maria Motta

2016-01-01

Full Text Available Dendritic cells are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. They do this by integrating stimuli from the environment and changing their functional status as a result of plasticity. The modifications suffered by these cells have consequences in the way the organism may respond. In the present work two opposing situations known to affect dendritic cells are analyzed: tumor growth, leading to a microenvironment that favors the induction of a tolerogenic profile, and organ transplantation, which leads to a proinflammatory profile. Lessons learned from these situations may help to understand the mechanisms of modulation resulting not only from the above circumstances, but also from other pathologies.

Engineering Functional Epithelium for Regenerative Medicine and In Vitro Organ Models: A Review

Science.gov (United States)

Vrana, Nihal E.; Lavalle, Philippe; Dokmeci, Mehmet R.; Dehghani, Fariba; Ghaemmaghami, Amir M.

2013-01-01

Recent advances in the fields of microfabrication, biomaterials, and tissue engineering have provided new opportunities for developing biomimetic and functional tissues with potential applications in disease modeling, drug discovery, and replacing damaged tissues. An intact epithelium plays an indispensable role in the functionality of several organs such as the trachea, esophagus, and cornea. Furthermore, the integrity of the epithelial barrier and its degree of differentiation would define the level of success in tissue engineering of other organs such as the bladder and the skin. In this review, we focus on the challenges and requirements associated with engineering of epithelial layers in different tissues. Functional epithelial layers can be achieved by methods such as cell sheets, cell homing, and in situ epithelialization. However, for organs composed of several tissues, other important factors such as (1) in vivo epithelial cell migration, (2) multicell-type differentiation within the epithelium, and (3) epithelial cell interactions with the underlying mesenchymal cells should also be considered. Recent successful clinical trials in tissue engineering of the trachea have highlighted the importance of a functional epithelium for long-term success and survival of tissue replacements. Hence, using the trachea as a model tissue in clinical use, we describe the optimal structure of an artificial epithelium as well as challenges of obtaining a fully functional epithelium in macroscale. One of the possible remedies to address such challenges is the use of bottom-up fabrication methods to obtain a functional epithelium. Modular approaches for the generation of functional epithelial layers are reviewed and other emerging applications of microscale epithelial tissue models for studying epithelial/mesenchymal interactions in healthy and diseased (e.g., cancer) tissues are described. These models can elucidate the epithelial/mesenchymal tissue interactions at the

Independent engineering review of the Hanford Waste Vitrification System

International Nuclear Information System (INIS)

1991-10-01

The Hanford Waste Vitrification Plant (HWVP) was initiated in June 1987. The HWVP is an essential element of the plan to end present interim storage practices for defense wastes and to provide for permanent disposal. The project start was justified, in part, on efficient technology and design information transfer from the prototype Defense Waste Processing Facility (DWPF). Development of other serial Hanford Waste Vitrification System (HWVS) elements, such as the waste retrieval system for the double-shell tanks (DSTs), and the pretreatment system to reduce the waste volume converted into glass, also was required to accomplish permanent waste disposal. In July 1991, at the time of this review, the HWVP was in the Title 2 design phase. The objective of this technical assessment is to determine whether the status of the technology development and engineering practice is sufficient to provide reasonable assurance that the HWVP and the balance of the HWVS system will operate in an efficient and cost-effective manner. The criteria used to facilitate a judgment of potential successful operation are: vitrification of high-level radioactive waste from specified DSTs on a reasonably continuous basis; and glass produced with physical and chemical properties formally acknowledge as being acceptable for disposal in a repository for high-level radioactive waste. The criteria were proposed specifically for the Independent Engineering Review to focus that assessment effort. They are not represented as the criteria by which the Department will judge the prudence of the Project. 78 refs., 10 figs., 12 tabs

Independent engineering review of the Hanford Waste Vitrification System

Energy Technology Data Exchange (ETDEWEB)

1991-10-01

The Hanford Waste Vitrification Plant (HWVP) was initiated in June 1987. The HWVP is an essential element of the plan to end present interim storage practices for defense wastes and to provide for permanent disposal. The project start was justified, in part, on efficient technology and design information transfer from the prototype Defense Waste Processing Facility (DWPF). Development of other serial Hanford Waste Vitrification System (HWVS) elements, such as the waste retrieval system for the double-shell tanks (DSTs), and the pretreatment system to reduce the waste volume converted into glass, also was required to accomplish permanent waste disposal. In July 1991, at the time of this review, the HWVP was in the Title 2 design phase. The objective of this technical assessment is to determine whether the status of the technology development and engineering practice is sufficient to provide reasonable assurance that the HWVP and the balance of the HWVS system will operate in an efficient and cost-effective manner. The criteria used to facilitate a judgment of potential successful operation are: vitrification of high-level radioactive waste from specified DSTs on a reasonably continuous basis; and glass produced with physical and chemical properties formally acknowledge as being acceptable for disposal in a repository for high-level radioactive waste. The criteria were proposed specifically for the Independent Engineering Review to focus that assessment effort. They are not represented as the criteria by which the Department will judge the prudence of the Project. 78 refs., 10 figs., 12 tabs.

Organic Rankine cycle – review and research directions in engine applications

Directory of Open Access Journals (Sweden)

Panesar Angad

2017-01-01

Full Text Available Waste heat to power conversion using Organic Rankine Cycles (ORC is expected to play an important role in CO2 reductions from diesel engines. Firstly, a review of automotive ORCs is presented focusing on the pure working fluids, thermal architectures and expanders. The discussion includes, but is not limited to: R245fa, ethanol and water as fluids; series, parallel and cascade as architectures; dry saturated, superheated and supercritical as expansion conditions; and scroll, radial turbine and piston as expansion machines. Secondly, research direction in versatile expander and holistic architecture (NOx + CO2 are proposed. Benefits of using the proposed unconventional approaches are quantified using Ricardo Wave and Aspen HYSYS for diesel engine and ORC modelling. Results indicate that, the implementation of versatile piston expander tolerant to two-phase and using cyclopentane can potentially increase the highway drive cycle power by 8%. Furthermore, holistic architecture offering complete utilisation of charge air and exhaust recirculation heat increased the performance noticeably to 5% of engine power at the design point condition.

Machining the Integral Impeller and Blisk of Aero-Engines: A Review of Surface Finishing and Strengthening Technologies

Science.gov (United States)

Fu, Youzhi; Gao, Hang; Wang, Xuanping; Guo, Dongming

2017-05-01

The integral impeller and blisk of an aero-engine are high performance parts with complex structure and made of difficult-to-cut materials. The blade surfaces of the integral impeller and blisk are functional surfaces for power transmission, and their surface integrity has significant effects on the aerodynamic efficiency and service life of an aero-engine. Thus, it is indispensable to finish and strengthen the blades before use. This paper presents a comprehensive literature review of studies on finishing and strengthening technologies for the impeller and blisk of aero-engines. The review includes independent and integrated finishing and strengthening technologies and discusses advanced rotational abrasive flow machining with back-pressure used for finishing the integral impeller and blisk. A brief assessment of future research problems and directions is also presented.

Review of durability of cementitious engineered barriers in repository environments

International Nuclear Information System (INIS)

Parrott, L.J.; Lawrence, C.D.

1992-01-01

This report is concerned with the durability of cementitious engineered barriers in a repository for low and intermediate level nuclear waste. Following the introduction the second section of the review identifies the environmental conditions associated with a deep, hard rock repository for ILW and LLW that are relevant to the durability of cementitious barriers. Section three examines the microstructure and macrostructure of cementitious materials and considers the physical and chemical processes of radionuclide immobilization. Potential repository applications and compositions of cementitious materials are reviewed in Section four. The main analysis of durability is dealt with in Section five. The different types of cementitious barrier are considered separately and their most probable modes of degradation are analysed. Concluding remarks that highlight critical technical matters are given in Section six. (author)

Evaluation of cage micro-environment of mice housed on various types of bedding materials.

Science.gov (United States)

Smith, Ellen; Stockwell, Jason D; Schweitzer, Isabelle; Langley, Stephen H; Smith, Abigail L

2004-07-01

A variety of environmental factors can affect the outcomes of studies using laboratory rodents. One such factor is bedding. Several new bedding materials and processing methods have been introduced to the market in recent years, but there are few reports of their performance. In the studies reported here, we have assessed the cage micro-environment (in-cage ammonia levels, temperature, and humidity) of mice housed on various kinds of bedding and their combinations. We also compared results for bedding supplied as Nestpaks versus loose bedding. We studied C57BL/6J mice (commonly used) and NOD/LtJ mice (heavy soilers) that were maintained, except in one study, in static duplex cages. In general, we observed little effect of bedding type on in-cage temperature or humidity; however, there was considerable variation in ammonia concentrations. The lowest ammonia concentrations occurred in cages housing mice on hardwood bedding or a mixture of corncob and alpha cellulose. In one experiment comparing the micro-environments of NOD/LtJ male mice housed on woodpulp fiber bedding in static versus ventilated caging, we showed a statistically significant decrease in ammonia concentrations in ventilated cages. Therefore, our data show that bedding type affects the micro-environment in static cages and that effects may differ for ventilated cages, which are being used in vivaria with increasing frequency. Copyright 2004 American Association for Laboratory Animal Science

Real-time monitoring of thermodynamic microenvironment in a pan coater.

Science.gov (United States)

Pandey, Preetanshu; Bindra, Dilbir S

2013-02-01

The current study demonstrates the use of tablet-size data logging devices (PyroButtons) to quantify the microenvironment experienced by tablets during pan coating process. PyroButtons were fixed at the inlet and exhaust plenums, and were also placed to freely move with the tablets. The effects of process parameters (spray rate and inlet-air humidity) on the thermodynamic conditions inside the pan coater were studied. It was shown that the same exhaust temperature (a parameter most commonly monitored and controlled during film coating) can be attained with very different tablet-bed conditions. The tablet-bed conditions were found to be more sensitive to the changes in spray rate as compared with the inlet-air humidity. Both spray rate and inlet-air humidity were shown to have an effect on the number of tablet defects (loss of logo definition), and a good correlation between number of tablet defects and tablet-bed humidity was observed. The ability to quantify the thermodynamic microenvironment experienced by the tablets during coating and be able to correlate that to macroscopic tablet defects can be an invaluable tool that can help to establish a process design space during product development. Copyright © 2012 Wiley Periodicals, Inc.

Metabolomics of the tumor microenvironment in pediatric acute lymphoblastic leukemia.

Directory of Open Access Journals (Sweden)

Stefano Tiziani

Full Text Available The tumor microenvironment is emerging as an important therapeutic target. Most studies, however, are focused on the protein components, and relatively little is known of how the microenvironmental metabolome might influence tumor survival. In this study, we examined the metabolic profiles of paired bone marrow (BM and peripheral blood (PB samples from 10 children with acute lymphoblastic leukemia (ALL. BM and PB samples from the same patient were collected at the time of diagnosis and after 29 days of induction therapy, at which point all patients were in remission. We employed two analytical platforms, high-resolution magnetic resonance spectroscopy and gas chromatography-mass spectrometry, to identify and quantify 102 metabolites in the BM and PB. Standard ALL therapy, which includes l-asparaginase, completely removed circulating asparagine, but not glutamine. Statistical analyses of metabolite correlations and network reconstructions showed that the untreated BM microenvironment was characterized by a significant network-level signature: a cluster of highly correlated lipids and metabolites involved in lipid metabolism (p<0.006. In contrast, the strongest correlations in the BM upon remission were observed among amino acid metabolites and derivatives (p<9.2 × 10(-10. This study provides evidence that metabolic characterization of the cancer niche could generate new hypotheses for the development of cancer therapies.

Recent advancements in electrospinning design for tissue engineering applications: A review.

Science.gov (United States)

Kishan, Alysha P; Cosgriff-Hernandez, Elizabeth M

2017-10-01

Electrospinning, a technique used to fabricate fibrous scaffolds, has gained popularity in recent years as a method to produce tissue engineered grafts with architectural similarities to the extracellular matrix. Beyond its versatility in material selection, electrospinning also provides many tools to tune the fiber morphology and scaffold geometry. Recent efforts have focused on extending the capabilities of electrospinning to produce scaffolds that better recapitulate tissue properties and enhance regeneration. This review highlights these advancements by providing an overview of the processing variables and setups used to modulate scaffold architecture, discussing strategies to improve cellular infiltration and guide cell behavior, and providing a summary of electrospinning applications in tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2892-2905, 2017. © 2017 Wiley Periodicals, Inc.

Feasibility of using less viscous and lower cetane (LVLC) fuels in a diesel engine: A review

KAUST Repository

Vallinayagam, R.

2015-11-01

This review work focuses on biofuels with lower viscosity and cetane number and their mode of operation in a diesel engine. Though there were a number of review works describing the production, characterization and utilization of biodiesel, synthesized from vegetable oils, a comprehensive summary on other category of biofuels endowed with lower viscosity and cetane number has not come to light so far. In this backdrop, this review work would bring forth the existence of biofuels having lower viscosity and cetane number, classify them under one category and elucidate their operational feasibility in a diesel engine. Considerably, alcohol based fuels such as methanol, ethanol and butanol, and plant based light biofuels such as eucalyptus oil and pine oil have been chosen and classified as LVLC (less viscous and lower cetane) fuels in the current work. Besides describing the operation feasibility of these fuels, an extensive exploration of their physical, thermal and critical properties as well as their compositional attributes has been made. Despite their distinct properties, these fuels have found use in diesel engine by various strategies and apparently, they could be used in blends with diesel/biodiesel, dual fuel mode and as sole fuel. In this regard, herein, a detailed summary on operation of these fuels in the reported three different modes is clearly explained and their engine characteristics such as performance, combustion and emission are briefed. © 2015 Elsevier Ltd.

Microcapsules and 3D customizable shelled microenvironments from laser direct-written microbeads.

Science.gov (United States)

Kingsley, David M; Dias, Andrew D; Corr, David T

2016-10-01

Microcapsules are shelled 3D microenvironments, with a liquid core. These core-shelled structures enable cell-cell contact, cellular proliferation and aggregation within the capsule, and can be utilized for controlled release of encapsulated contents. Traditional microcapsule fabrication methods provide limited control of capsule size, and are unable to control capsule placement. To overcome these limitations, we demonstrate size and spatial control of poly-l-lysine and chitosan microcapsules, using laser direct-write (LDW) printing, and subsequent processing, of alginate microbeads. Additionally, microbeads were used as volume pixels (voxels) to form continuous 3D hydrogel structures, which were processed like capsules, to form custom shelled aqueous-core 3D structures of prescribed geometry; such as strands, rings, and bifurcations. Heterogeneous structures were also created with controlled initial locations of different cell types, to demonstrate the ability to prescribe cell signaling (heterotypic and homotypic) in co-culture conditions. Herein, we demonstrate LDW's ability to fabricate intricate 3D structures, essentially with "printed macroporosity," and to precisely control structural composition by bottom-up fabrication in a bead-by-bead manner. The structural and compositional control afforded by this process enables the creation of a wide range of new constructs, with many potential applications in tissue engineering and regenerative medicine. Biotechnol. Bioeng. 2016;113: 2264-2274. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. Introduction of a multiinstitutional research project

International Nuclear Information System (INIS)

Zips, D.; Petersen, C.; Adam, M.; Molls, M.; Philbrook, C.; Flentje, M.; Haase, A.; Schmitt, P.; Mueller-Klieser, W.; Thews, O.; Walenta, S.; Baumann, M.

2004-01-01

Background: recent developments in imaging technology and tumor biology have led to new techniques to detect hypoxia and related alterations of the metabolic microenvironment in tumors. However, whether these new methods can predict radiobiological hypoxia and outcome after fractionated radiotherapy still awaits experimental evaluation. Material and methods: the present article will introduce a multiinstitutional research project addressing the impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. The four laboratories involved are situated at the universities of Dresden, Mainz, Munich and Wuerzburg, Germany. Results: the joint scientific project started to collect data obtained on a set of ten different human tumor xenografts growing in nude mice by applying various imaging techniques to detect tumor hypoxia and related parameters of the metabolic microenvironment. These techniques include magnetic resonance imaging and spectroscopy, metabolic mapping with quantitative bioluminescence and single-photon imaging, histological multiparameter analysis of biochemical hypoxia, perfusion and vasculature, and immunohistochemistry of factors related to angiogenesis, invasion and metastasis. To evaluate the different methods, baseline functional radiobiological data including radiobiological hypoxic fraction and outcome after fractionated irradiation will be determined. Conclusion: besides increasing our understanding of tumor biology, the project will focus on new, clinically applicable strategies for microenvironment profiling and will help to identify those patients that might benefit from targeted interventions to improve tumor oxygenation. (orig.)

Disruption of in vivo chronic lymphocytic leukemia tumor-microenvironment interactions by ibrutinib - findings from an investigator initiated phase 2 study

DEFF Research Database (Denmark)

Niemann, Carsten U; Herman, Sarah E M; Maric, Irina

2016-01-01

PURPOSE: Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental interactions for proliferation and survival that are at least partially mediated through B cell receptor (BCR) signaling. Ibrutinib, a Bruton's tyrosine kinase inhibitor, disrupts BCR signaling and leads to the egress...... of tumor cells from the microenvironment. While the on-target effects on CLL cells are well defined, the impact on the microenvironment is less well studied. We therefore sought to characterize the in vivo effects of ibrutinib on the tumor microenvironment. EXPERIMENTAL DESIGN: Patients received single...... agent ibrutinib on an investigator-initiated phase 2 trial. Serial blood and tissue samples were collected pre-treatment and during treatment. Changes in cytokine levels, cellular subsets and microenvironmental interactions were assessed. RESULTS: Serum levels of key chemokines and inflammatory...

The inflammatory milieu within the pancreatic cancer microenvironment correlates with clinicopathologic parameters, chemoresistance and survival

International Nuclear Information System (INIS)

Delitto, Daniel; Black, Brian S.; Sorenson, Heather L.; Knowlton, Andrea E.; Thomas, Ryan M.; Sarosi, George A.; Moldawer, Lyle L.; Behrns, Kevin E.; Liu, Chen; George, Thomas J.; Trevino, Jose G.; Wallet, Shannon M.; Hughes, Steven J.

2015-01-01

The tumor microenvironment impacts pancreatic cancer (PC) development, progression and metastasis. How intratumoral inflammatory mediators modulate this biology remains poorly understood. We hypothesized that the inflammatory milieu within the PC microenvironment would correlate with clinicopathologic findings and survival. Pancreatic specimens from normal pancreas (n = 6), chronic pancreatitis (n = 9) and pancreatic adenocarcinoma (n = 36) were homogenized immediately upon resection. Homogenates were subjected to multiplex analysis of 41 inflammatory mediators. Twenty-three mediators were significantly elevated in adenocarcinoma specimens compared to nonmalignant controls. Increased intratumoral IL-8 concentrations associated with larger tumors (P = .045) and poor differentiation (P = .038); the administration of neoadjuvant chemotherapy associated with reduced IL-8 concentrations (P = .003). Neoadjuvant therapy was also associated with elevated concentrations of Flt-3 L (P = .005). Elevated levels of pro-inflammatory cytokines IL-1β (P = .017) and TNFα (P = .033) were associated with a poor histopathologic response to neoadjuvant therapy. Elevated concentrations of G-CSF (P = .016) and PDGF-AA (P = .012) correlated with reduced overall survival. Conversely, elevated concentrations of FGF-2 (P = .038), TNFα (P = .031) and MIP-1α (P = .036) were associated with prolonged survival. The pancreatic cancer microenvironment harbors a unique inflammatory milieu with potential diagnostic and prognostic value

Biodiesel from plant seed oils as an alternate fuel for compression ignition engines-a review.

Science.gov (United States)

Vijayakumar, C; Ramesh, M; Murugesan, A; Panneerselvam, N; Subramaniam, D; Bharathiraja, M

2016-12-01

The modern scenario reveals that the world is facing energy crisis due to the dwindling sources of fossil fuels. Environment protection agencies are more concerned about the atmospheric pollution due to the burning of fossil fuels. Alternative fuel research is getting augmented because of the above reasons. Plant seed oils (vegetable oils) are cleaner, sustainable, and renewable. So, it can be the most suitable alternative fuel for compression ignition (CI) engines. This paper reviews the availability of different types of plant seed oils, several methods for production of biodiesel from vegetable oils, and its properties. The different types of oils considered in this review are cashew nut shell liquid (CNSL) oil, ginger oil, eucalyptus oil, rice bran oil, Calophyllum inophyllum, hazelnut oil, sesame oil, clove stem oil, sardine oil, honge oil, polanga oil, mahua oil, rubber seed oil, cotton seed oil, neem oil, jatropha oil, egunsi melon oil, shea butter, linseed oil, Mohr oil, sea lemon oil, pumpkin oil, tobacco seed oil, jojoba oil, and mustard oil. Several methods for production of biodiesel are transesterification, pre-treatment, pyrolysis, and water emulsion are discussed. The various fuel properties considered for review such as specific gravity, viscosity, calorific value, flash point, and fire point are presented. The review also portrays advantages, limitations, performance, and emission characteristics of engine using plant seed oil biodiesel are discussed. Finally, the modeling and optimization of engine for various biofuels with different input and output parameters using artificial neural network, response surface methodology, and Taguchi are included.

Metastasis in context : modeling the tumor microenvironment with cancer-on-a-chip approaches

NARCIS (Netherlands)

Sleeboom, Jelle J.F.; Amirabadi, Hossein Eslami; Nair, Poornima; Sahlgren, Cecilia M.; Den Toonder, Jaap M.J.

2018-01-01

Most cancer deaths are not caused by the primary tumor, but by secondary tumors formed through metastasis, a complex and poorly understood process. Cues from the tumor microenvironment, such as the biochemical composition, cellular population, extracellular matrix, and tissue (fluid) mechanics, have

Internal combustion engines history - a review

International Nuclear Information System (INIS)

Gaviria Rios, Jorge Enrique; Mora Guzman, Jorge Hernan; Agudelo, John Ramiro

2002-01-01

In this article, a chronological analysis of the technologies and events that any way influenced in the evolution of the internal combustion engine is done everything it through the observation of the works carried out for scientific empiric and engineers whose technical and conceptual value meant the motivation of other people for the search of a better development in this engineering field

Melanoma cell-derived exosomes promote epithelial-mesenchymal transition in primary melanocytes through paracrine/autocrine signaling in the tumor microenvironment

Science.gov (United States)

Xiao, Deyi; Barry, Samantha; Kmetz, Daniel; Egger, Michael; Pan, Jianmin; Rai, Shesh N; Qu, Jifu; McMasters, Kelly M.; Hao, Hongying

2016-01-01

The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma. PMID:27063098

Effect of Microenvironment on Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Hepatocytes In Vitro and In Vivo

Directory of Open Access Journals (Sweden)

Gai Xue

2016-01-01

Full Text Available Human umbilical cord-derived mesenchymal stem cells (hUCMSCs are considered to be an ideal cell source for cell therapy of many diseases. The aim of this study was to investigate the contribution of the microenvironment to the hepatic differentiation potential of hUCMSCs in vitro and in vivo and to explore their therapeutic use in acute liver injury in rats. We established a new model to simulate the liver tissue microenvironment in vivo using liver homogenate supernatant (LHS in vitro. This induced environment could drive hUCMSCs to differentiate into hepatocyte-like cells within 7 days. The differentiated cells expressed hepatocyte-specific markers and demonstrated hepatocellular functions. We also injected hUCMSCs into rats with CCl4-induced acute hepatic injury. The hUCMSCs were detected in the livers of recipient rats and expressed the human hepatocyte-specific markers, suggesting that hUCMSCs could differentiate into hepatocyte-like cells in vivo in the liver tissue microenvironment. Levels of biochemistry markers improved significantly after transplantation of hUCMSCs compared with the nontransplantation group (P<0.05. In conclusion, this study demonstrated that the liver tissue microenvironment may contribute to the differentiation of hUCMSCs into hepatocytes both in vitro and in vivo.

Effect of Microenvironment on Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Hepatocytes In Vitro and In Vivo

Science.gov (United States)

Xue, Gai; Han, Xiaolei; Ma, Xin; Wu, Honghai; Qin, Yabin; Liu, Jianfang; Hu, Yuqin; Hong, Yang; Hou, Yanning

2016-01-01

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are considered to be an ideal cell source for cell therapy of many diseases. The aim of this study was to investigate the contribution of the microenvironment to the hepatic differentiation potential of hUCMSCs in vitro and in vivo and to explore their therapeutic use in acute liver injury in rats. We established a new model to simulate the liver tissue microenvironment in vivo using liver homogenate supernatant (LHS) in vitro. This induced environment could drive hUCMSCs to differentiate into hepatocyte-like cells within 7 days. The differentiated cells expressed hepatocyte-specific markers and demonstrated hepatocellular functions. We also injected hUCMSCs into rats with CCl4-induced acute hepatic injury. The hUCMSCs were detected in the livers of recipient rats and expressed the human hepatocyte-specific markers, suggesting that hUCMSCs could differentiate into hepatocyte-like cells in vivo in the liver tissue microenvironment. Levels of biochemistry markers improved significantly after transplantation of hUCMSCs compared with the nontransplantation group (P < 0.05). In conclusion, this study demonstrated that the liver tissue microenvironment may contribute to the differentiation of hUCMSCs into hepatocytes both in vitro and in vivo. PMID:27088093

The Immunomodulatory Effects of Mesenchymal Stem Cell Polarization within the Tumor Microenvironment Niche

Directory of Open Access Journals (Sweden)

Cosette M. Rivera-Cruz

2017-01-01

Full Text Available Mesenchymal stem cells (MSCs represent a promising tool for cell therapy, particularly for their antitumor effects. This cell population can be isolated from multiple tissue sources and also display an innate ability to home to areas of inflammation, such as tumors. Upon entry into the tumor microenvironment niche, MSCs promote or inhibit tumor progression by various mechanisms, largely through the release of soluble factors. These factors can be immunomodulatory by activating or inhibiting both the adaptive and innate immune responses. The mechanisms by which MSCs modulate the immune response are not well understood. Because of this, the relationship between MSCs and immune cells within the tumor microenvironment niche continues to be an active area of research in order to help explain the apparent contradictory findings currently available in the literature. The ongoing research aims to enhance the potential of MSCs in future therapeutic applications.

Elimination of Coast Guard plan review for non-critical engineering systems and cargo barges

Science.gov (United States)

1994-06-21

The purpose of this Circular is to publish policy that provides for the elimination of Coast Guard review and approval of certain engineering system drawings for all vessels as well as structural drawings for Coast Guard inspected non-self propelled ...

Oxygen microenvironment affects the uptake of nanoparticles in head and neck tumor cells

Science.gov (United States)

Chen, Eunice Y.; Hodge, Sasson; Tai, Katherine; Hou, Huagang; Khan, Nadeem; Hoopes, P. Jack; Samkoe, Kimberley S.

2013-02-01

Survival of head and neck cancer patients has not improved in several decades despite advances in diagnostic and therapeutic techniques. Tumor hypoxia in head and neck cancers is a critical factor that leads to poor prognosis, resistance to radiation and chemotherapies, and increased metastatic potential. Magnetic nanoparticle hyperthermia (mNPHT) is a promising therapy for hypoxic tumors because nanoparticles (NP) can be directly injected into, or targeted to, hypoxic tumor cells and exposed to alternating magnetic fields (AMF) to induce hyperthermia. Magnetic NPHT can improve therapeutic effectiveness by two modes of action: 1) direct killing of hypoxic tumor cells; and 2) increase in tumor oxygenation, which has the potential to make the tumor more susceptible to adjuvant therapies such as radiation and chemotherapy. Prior studies in breast cancer cells demonstrated that a hypoxic microenvironment diminished NP uptake in vitro; however, mNPHT with intratumoral NP injection in hypoxic tumors increased tumor oxygenation and delayed tumor growth. In this study, head and neck squamous cell carcinoma (HNSCC) cell lines were incubated in normoxic, hypoxic, and hyperoxic conditions with iron oxide NP for 4-72 hours. After incubation, the cells were analyzed for iron uptake by mass spectrometry, Prussian blue staining, and electron microscopy. In contrast to breast cancer cells, uptake of NPs was increased in hypoxic microenvironments as compared to normoxic conditions in HNSCC cells. In future studies, we will confirm the effect of the oxygen microenvironment on NP uptake and efficacy of mNPHT both in vitro and in vivo.

Inflammatory models drastically alter tumor growth and the immune microenvironment in hepatocellular carcinoma.

Science.gov (United States)

Markowitz, Geoffrey J; Michelotti, Gregory A; Diehl, Anna Mae; Wang, Xiao-Fan

2015-04-01

Initiation and progression of hepatocellular carcinoma (HCC) is intimately associated with a chronically diseased liver tissue. This diseased liver tissue background is a drastically different microenvironment from the healthy liver, especially with regard to immune cell prevalence and presence of mediators of immune function. To better understand the consequences of liver disease on tumor growth and the interplay with its microenvironment, we utilized two standard methods of fibrosis induction and orthotopic implantation of tumors into the inflamed and fibrotic liver to mimic the liver condition in human HCC patients. Compared to non-diseased controls, tumor growth was significantly enhanced under fibrotic conditions. The immune cells that infiltrated the tumors were also drastically different, with decreased numbers of natural killer cells but greatly increased numbers of immune-suppressive CD11b + Gr1 hi myeloid cells in both models of fibrosis. In addition, there were model-specific differences: Increased numbers of CD11b + myeloid cells and CD4 + CD25 + T cells were found in tumors in the bile duct ligation model but not in the carbon tetrachloride model. Induction of fibrosis altered the cytokine production of implanted tumor cells, which could have farreaching consequences on the immune infiltrate and its functionality. Taken together, this work demonstrates that the combination of fibrosis induction with orthotopic tumor implantation results in a markedly different tumor microenvironment and tumor growth kinetics, emphasizing the necessity for more accurate modeling of HCC progression in mice, which takes into account the drastic changes in the tissue caused by chronic liver disease.

Wnt ligand presentation and reception: from the stem cell niche to tissue engineering.

Science.gov (United States)

Mills, Kate M; Szczerkowski, James L A; Habib, Shukry J

2017-08-01

Stem cells reside in niches where spatially restricted signals maintain a delicate balance between stem cell self-renewal and differentiation. Wnt family proteins are particularly suited for this role as they are modified by lipids, which constrain and spatially regulate their signalling range. In recent years, Wnt/β-catenin signalling has been shown to be essential for the self-renewal of a variety of mammalian stem cells. In this review, we discuss Wnt-responsive stem cells in their niche, and mechanisms by which Wnt ligands are presented to responsive cells. We also highlight recent progress in molecular visualization that has allowed for the monitoring of Wnt signalling within the stem cell compartment and new approaches to recapitulate this niche signalling in vitro Indeed, new technologies that present Wnt in a localized manner and mimic the three-dimensional microenvironment of stem cells will advance our understanding of Wnt signalling in the stem cell niche. These advances will expand current horizons to exploit Wnt ligands in the rapidly evolving fields of tissue engineering and regenerative medicine. © 2017 The Authors.

Exosome-Based Cell-Cell Communication in the Tumor Microenvironment

Directory of Open Access Journals (Sweden)

Joana Maia

2018-02-01

Full Text Available Tumors are not isolated entities, but complex systemic networks involving cell-cell communication between transformed and non-transformed cells. The milieu created by tumor-associated cells may either support or halt tumor progression. In addition to cell-cell contact, cells communicate through secreted factors via a highly complex system involving characteristics such as ligand concentration, receptor expression and integration of diverse signaling pathways. Of these, extracellular vesicles, such as exosomes, are emerging as novel cell-cell communication mediators in physiological and pathological scenarios. Exosomes, membrane vesicles of endocytic origin released by all cells (both healthy and diseased, ranging in size from 30 to 150 nm, transport all the main biomolecules, including lipids, proteins, DNAs, messenger RNAs and microRNA, and perform intercellular transfer of components, locally and systemically. By acting not only in tumor cells, but also in tumor-associated cells such as fibroblasts, endothelium, leukocytes and progenitor cells, tumor- and non-tumor cells-derived exosomes have emerged as new players in tumor growth and invasion, tumor-associated angiogenesis, tissue inflammation and immunologic remodeling. In addition, due to their property of carrying molecules from their cell of origin to the peripheral circulation, exosomes have been increasingly studied as sources of tumor biomarkers in liquid biopsies. Here we review the current literature on the participation of exosomes in the communication between tumor and tumor-associated cells, highlighting the role of this process in the setup of tumor microenvironments that modulate tumor initiation and metastasis.

Review of Microfluidic Photobioreactor Technology for Metabolic Engineering and Synthetic Biology of Cyanobacteria and Microalgae

Directory of Open Access Journals (Sweden)

Ya-Tang Yang

2016-10-01

Full Text Available One goal of metabolic engineering and synthetic biology for cyanobacteria and microalgae is to engineer strains that can optimally produce biofuels and commodity chemicals. However, the current workflow is slow and labor intensive with respect to assembly of genetic parts and characterization of production yields because of the slow growth rates of these organisms. Here, we review recent progress in the microfluidic photobioreactors and identify opportunities and unmet needs in metabolic engineering and synthetic biology. Because of the unprecedented experimental resolution down to the single cell level, long-term real-time monitoring capability, and high throughput with low cost, microfluidic photobioreactor technology will be an indispensible tool to speed up the development process, advance fundamental knowledge, and realize the full potential of metabolic engineering and synthetic biology for cyanobacteria and microalgae.

3D Printing of Tissue Engineered Constructs for in vitro Modeling of Disease Progression and Drug Screening

Science.gov (United States)

Vanderburgh, Joseph; Sterling, Julie A.

2016-01-01

2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D versus 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design (CAD) file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs (TECs) that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs. PMID:27169894

VOC source identification from personal and residential indoor, outdoor and workplace microenvironment samples in EXPOLIS-Helsinki, Finland

Energy Technology Data Exchange (ETDEWEB)

Edwards, Rufus D. [KTL-Finnish National Inst. of Public Health, Dept. of Environmental Hygiene, Kuopio (Finland); California Univ., School of Public Health, Berkeley, CA (United States); Jurvelin, J. [KTL-Finnish National Inst. of Public Health, Dept. of Environmental Hygiene, Kuopio (Finland); Jyvaeskylae Polytechnic, School of Engineering and Technology, Jyvaeskylae (Finland); Koistinen, K. [KTL-Finnish National Inst. of Public Health, Dept. of Environmental Hygiene, Kuopio (Finland); Saarela, K. [VTT, Chemical Technology, Espoo (Finland); Jantunen, M. [EC JRC, Inst. of the Environment, Ispra (Italy)

2001-07-01

Principal component analyses (varimax rotation) were used to identify common sources of 30 target volatile organic compounds (VOCs) in residential outdoor, residential indoor and workplace microenvironment and personal 48-h exposure samples, as a component of the EXPOLIS-Helsinki study. Variability in VOC concentrations in residential outdoor microenvironments was dominated by compounds associated with long-range transport of pollutants, followed by traffic emissions, emissions from trees and product emissions. Variability in VOC concentrations in environmental tobacco smoke (ETS) free residential indoor environments was dominated by compounds associated with indoor cleaning products, followed by compounds associated with traffic emissions, long-range transport of pollutants and product emissions. Median indoor/outdoor ratios for compounds typically associated with traffic emissions and long-range transport of pollutants exceeded 1, in some cases quite considerably, indicating substantial indoor source contributions. Changes in the median indoor/outdoor ratios during different seasons reflected different seasonal ventilation patterns as increased ventilation led to dilution of those VOC compounds in the indoor environment that had indoor sources. Variability in workplace VOC concentrations was dominated by compounds associated with traffic emissions followed by product emissions, long-range transport and air fresheners. Variability in VOC concentrations in ETS free personal exposure samples was dominated by compounds associated with traffic emissions, followed by long-range transport, cleaning products and product emissions. VOC sources in personal exposure samples reflected the times spent in different microenvironments, and personal exposure samples were not adequately represented by any one microenvironment, demonstrating the need for personal exposure sampling. (Author)

Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

International Nuclear Information System (INIS)

Hamm, Christopher A; Wang, Deli; Malchenko, Sergey; Fatima Bonaldo, Maria de; Casavant, Thomas L; Hendrix, Mary JC; Soares, Marcelo B; Stevens, Jeff W; Xie, Hehuang; Vanin, Elio F; Morcuende, Jose A; Abdulkawy, Hakeem; Seftor, Elisabeth A; Sredni, Simone T; Bischof, Jared M

2010-01-01

Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC) - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis

Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

Directory of Open Access Journals (Sweden)

Hamm Christopher A

2010-09-01

Full Text Available Abstract Background Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. Methods To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. Results The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. Conclusion This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that

An abnormal bone marrow microenvironment contributes to hematopoietic dysfunction in Fanconi anemia.

Science.gov (United States)

Zhou, Yuan; He, Yongzheng; Xing, Wen; Zhang, Peng; Shi, Hui; Chen, Shi; Shi, Jun; Bai, Jie; Rhodes, Steven D; Zhang, Fengqui; Yuan, Jin; Yang, Xianlin; Zhu, Xiaofan; Li, Yan; Hanenberg, Helmut; Xu, Mingjiang; Robertson, Kent A; Yuan, Weiping; Nalepa, Grzegorz; Cheng, Tao; Clapp, D Wade; Yang, Feng-Chun

2017-06-01

Fanconi anemia is a complex heterogeneous genetic disorder with a high incidence of bone marrow failure, clonal evolution to acute myeloid leukemia and mesenchymal-derived congenital anomalies. Increasing evidence in Fanconi anemia and other genetic disorders points towards an interdependence of skeletal and hematopoietic development, yet the impact of the marrow microenvironment in the pathogenesis of the bone marrow failure in Fanconi anemia remains unclear. Here we demonstrated that mice with double knockout of both Fancc and Fancg genes had decreased bone formation at least partially due to impaired osteoblast differentiation from mesenchymal stem/progenitor cells. Mesenchymal stem/progenitor cells from the double knockout mice showed impaired hematopoietic supportive activity. Mesenchymal stem/progenitor cells of patients with Fanconi anemia exhibited similar cellular deficits, including increased senescence, reduced proliferation, impaired osteoblast differentiation and defective hematopoietic stem/progenitor cell supportive activity. Collectively, these studies provide unique insights into the physiological significance of mesenchymal stem/progenitor cells in supporting the marrow microenvironment, which is potentially of broad relevance in hematopoietic stem cell transplantation. Copyright© Ferrata Storti Foundation.

Graphical User Interfaces Reverse Engineering for Requirements Elicitation - Literature Review

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Carol Jaimes

2016-06-01

Full Text Available This paper exhibits a synthesis of the use of legacy systems GUI reverse engineering as a tool to software requirements elicitation. It presents a literature review describing the approaches related to the topic. This work primary goal is to determine the major investigations in this area, and if there are techniques focused exclusively on the observation of the legacy applications GUI to obtain software requirements in a standard format, without the use of source code, data structures, documentation or sophisticated algorithms for the application analysis.

Heterogeneity of passenger exposure to air pollutants in public transport microenvironments

Science.gov (United States)

Yang, Fenhuan; Kaul, Daya; Wong, Ka Chun; Westerdahl, Dane; Sun, Li; Ho, Kin-fai; Tian, Linwei; Brimblecombe, Peter; Ning, Zhi

2015-05-01

Epidemiologic studies have linked human exposure to pollutants with adverse health effects. Passenger exposure in public transport systems contributes an important fraction of daily burden of air pollutants. While there is extensive literature reporting the concentrations of pollutants in public transport systems in different cities, there are few studies systematically addressing the heterogeneity of passenger exposure in different transit microenvironments, in cabins of different transit vehicles and in areas with different characteristics. The present study investigated PM2.5 (particulate matter with aerodynamic diameters smaller than 2.5 μm), black carbon (BC), ultrafine particles (UFP) and carbon monoxide (CO) pollutant concentrations in various public road transport systems in highly urbanized city of Hong Kong. Using a trolley case housing numerous portable air monitors, we conducted a total of 119 trips during the campaign. Transit microenvironments, classified as 1). busy and secondary roadside bus stops; 2). open and enclosed termini; 3). above- and under-ground Motor Rail Transport (MTR) platforms, were investigated and compared to identify the factors that may affect passenger exposures. The pollutants inside bus and MTR cabins were also investigated together with a comparison of time integrated exposure between the transit modes. Busy roadside and enclosed termini demonstrated the highest average particle concentrations while the lowest was found on the MTR platforms. Traffic-related pollutants BC, UFP and CO showed larger variations than PM2.5 across different microenvironments and areas confirming their heterogeneity in urban environments. In-cabin pollutant concentrations showed distinct patterns with BC and UFP high in diesel bus cabins and CO high in LPG bus cabins, suggesting possible self-pollution issues and/or penetration of on-road pollutants inside cabins during bus transit. The total passenger exposure along selected routes, showed bus

Peritoneal inflammation – A microenvironment for Epithelial Ovarian Cancer (EOC

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Liu Jinsong

2004-06-01

Full Text Available Abstract Epithelial ovarian cancer (EOC is a significant cause of cancer related morbidity and mortality in women. Preferential involvement of peritoneal structures contributes to the overall poor outcome in EOC patients. Advances in biotechnology, such as cDNA microarray, are a product of the Human Genome Project and are beginning to provide fresh opportunities to understand the biology of EOC. In particular, it is now possible to examine in depth, at the molecular level, the complex relationship between the tumor itself and its surrounding microenvironment. This review focuses on the anatomy, physiology, and current immunobiologic research of peritoneal structures, and addresses certain potentially useful animal models. Changes in both the inflammatory and non-inflammatory cell compartments, as well as alterations to the extracellular matrix, appear to be signal events that contribute to the remodeling effects of the peritoneal stroma and surface epithelial cells on tumor growth and spread. These alterations may involve a number of proteins, including cytokines, chemokines, growth factors, either membrane or non-membrane bound, and integrins. Interactions between these molecules and molecular structures within the extracellular matrix, such as collagens and the proteoglycans, may contribute to a peritoneal mesothelial surface and stromal environment that is conducive to tumor cell proliferation and invasion. These alterations need to be examined and defined as possible prosnosticators and as therapeutic or diagnostic targets.

Report of the Review Committee of the R and D subjects on Computational Science and Engineering

International Nuclear Information System (INIS)

1999-08-01

The Ad Hoc Review Committee composed of seven experts was set up under the Research Evaluation Committee of JAERI in order to review the R and D subjects to be implemented for five years starting in a 2000 fiscal year at the Center for promotion of Computational Science and Engineering. The review meeting took place on April 26, 1999. According to the review methods consisting of review items, points of review and review criteria given by the Research Evaluation Committee, the review was conducted based on the materials submitted in advance and presentations of CCSE. The Research Evaluation Committee received the review report and its explanations from the Review Committee on July 5. The Research Evaluation Committee has acknowledged appropriateness of the review results. This report describes the review results. (author)

Precipitation in Powder Metallurgy, Nickel Base Superalloys: Review of Modeling Approach and Formulation of Engineering (Postprint)

Science.gov (United States)

2016-12-01

AFRL-RX-WP-JA-2016-0333 PRECIPITATION IN POWDER- METALLURGY , NICKEL-BASE SUPERALLOYS: REVIEW OF MODELING APPROACH AND FORMULATION OF...PRECIPITATION IN POWDER- METALLURGY , NICKEL- BASE SUPERALLOYS: REVIEW OF MODELING APPROACH AND FORMULATION OF ENGINEERING (POSTPRINT) 5a...and kinetic parameters required for the modeling of γ′ precipitation in powder- metallurgy (PM), nickel-base superalloys are summarized. These

Mimicking the micro-environment. Construction and evaluation of complex collagen-based scaffolds for tissue engineering

NARCIS (Netherlands)

Nillesen, S.T.M.

2012-01-01

The ultimate goal in tissue engineering is to create biomaterials that mimic normal tissue or are able to encourage cells cells to generate new functional tissue. For these biomaterials, it is important to use highly purified components in order to moderate the tissue response and to control the

Hypoxia Pathway Proteins As Central Mediators of Metabolism in the Tumor Cells and Their Microenvironment

Directory of Open Access Journals (Sweden)

Sundary Sormendi

2018-01-01

Full Text Available Low oxygen tension or hypoxia is a determining factor in the course of many different processes in animals, including when tissue expansion and cellular metabolism result in high oxygen demands that exceed its supply. This is mainly happening when cells actively proliferate and the proliferating mass becomes distant from the blood vessels, such as in growing tumors. Metabolic alterations in response to hypoxia can be triggered in a direct manner, such as the switch from oxidative phosphorylation to glycolysis or inhibition of fatty acid desaturation. However, as the modulated action of hypoxia-inducible factors or the oxygen sensors (prolyl hydroxylase domain-containing enzymes can also lead to changes in enzyme expression, these metabolic changes can also be indirect. With this review, we want to summarize our current knowledge of the hypoxia-induced changes in metabolism during cancer development, how they are affected in the tumor cells and in the cells of the microenvironment, most prominently in immune cells.

A review of fibrin and fibrin composites for bone tissue engineering

Directory of Open Access Journals (Sweden)

Noori A

2017-07-01

Full Text Available Alireza Noori,1 Seyed Jamal Ashrafi,2 Roza Vaez-Ghaemi,3 Ashraf Hatamian-Zaremi,4 Thomas J Webster5 1Department of Tissue Engineering and Applied Cell Sciences, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 2School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran; 3Department of Chemical and Biological Engineering, Faculty of Biomedical Engineering, The University of British Columbia, Vancouver, BC, Canada; 4Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran; 5Department of Chemical Engineering, Northeastern University, Boston, MA, USA Abstract: Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels, there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient’s own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the

Gamma irradiation of the fetus damages the developing hemopoietic microenvironment rather than the hemopoietic progenitor cells

International Nuclear Information System (INIS)

Yang, F.T.; Lord, B.I.; Hendry, J.H.

1995-01-01

Hemopoiesis is the product of two components: the hemopoietic tissue and the regulatory stromal microenvironment in which it resides. Plutonium-239, incorporated during fetal development in mice, is known to cause deficient hemopoiesis. A predetermined equivalent γ-ray dose has now been used in combination with cross-transplantation experiments to separate these two components and define where the damage arises. It was confirmed that 1.8 Gy γ irradiation at midterm gestation caused a 40% reduction in the hemopoietic stem (spleen colony-forming) cell population of their offspring which persisted to at least 24 weeks of age. Spleen colony formation after sublethal doses of γ rays reflected this reduced complement of endogenous stem cells. The regulatory hemopoietic microenvironment, measured as fibroblastoid colony-forming cells, was similarly depleted. Normal growth of the CFU-S population after transplantation into standard recipients showed that the quality of the stem cell population in the offspring of irradiated mothers was not affected. By contrast, when used as recipients of a bone marrow transplant from either normal or irradiated offspring, the offspring of irradiated mothers were unable to support normal growth: there was a twofold difference in the number of CFU-S per femur for at least 100 days after transplantation. There were 70% fewer CFU-F in the femur 1 month after bone marrow transplantation when the offspring of irradiated mothers were used as transplant recipients compared to when normal offspring were used. This not only confirmed their reduced capacity to host normal stem cells but also indicated that CFU-F in the transplant were unable to compensate for the poor microenvironment in the irradiated offspring hosts. It is concluded that irradiation at midterm gestation damages the developing regulatory microenvironment but not the hemopoietic stem cell population that it hosts. 12 refs., 1 fig., 4 tabs

Use of crude filtered vegetable oil as a fuel in diesel engines state of the art: Literature review

Energy Technology Data Exchange (ETDEWEB)

Sidibe, S.S.; Azoumah, Y. [Institut Internationale d' ingenierie de l' Eau et de l' Environnement (2iE), rue de science 01 Ouagadougou 01 BP 594 (Burkina Faso); Blin, J. [Institut Internationale d' ingenierie de l' Eau et de l' Environnement (2iE), rue de science 01 Ouagadougou 01 BP 594 (Burkina Faso); Centre International de Recherche Agronomique pour le Developpement (CIRAD), UPR Biomasse energie, TA B-42/16, 73 rue JF Breton, 34398 Montpellier Cedex 5 (France); Vaitilingom, G. [Centre International de Recherche Agronomique pour le Developpement (CIRAD), UPR Biomasse energie, TA B-42/16, 73 rue JF Breton, 34398 Montpellier Cedex 5 (France)

2010-12-15

Many studies have been published on vegetable oil use in diesel engines. The different authors unanimously acknowledge the potential and merits of this renewable fuel. Typically, Straight Vegetable Oils (SVOs) produced locally on a small scale, have proven to be easy to produce with very little environmental impact. However, as their physico-chemical characteristics differ from those of diesel oil, their use in diesel engines can lead to a certain number of technical problems over time. In bibliography, there is substantial disagreement between authors regarding the advanced phenomena linked to this problems and the recommended solutions. Some of these publications treat options individually without any real comparison between them. Another observation is that the literature rarely tackles problems linked to vegetable oil quality. This paper sets out to review the state of the art for SVO use as fuel in diesel engines, based on a bibliographic study (literature review). The first section of the document examines the influence of the type and quality of vegetable oils for fuel use in diesel engines. The second section discusses the advantages and disadvantages of two options recommended for SVO use in diesel engines: dual fuelling and blending with diesel fuel. (author)

Disruption of in vivo Chronic Lymphocytic Leukemia Tumor-Microenvironment Interactions by Ibrutinib--Findings from an Investigator-Initiated Phase II Study.

Science.gov (United States)

Niemann, Carsten U; Herman, Sarah E M; Maric, Irina; Gomez-Rodriguez, Julio; Biancotto, Angelique; Chang, Betty Y; Martyr, Sabrina; Stetler-Stevenson, Maryalice; Yuan, Constance M; Calvo, Katherine R; Braylan, Raul C; Valdez, Janet; Lee, Yuh Shan; Wong, Deanna H; Jones, Jade; Sun, Clare; Marti, Gerald E; Farooqui, Mohammed Z H; Wiestner, Adrian

2016-04-01

Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental interactions for proliferation and survival that are at least partially mediated through B-cell receptor (BCR) signaling. Ibrutinib, a Bruton tyrosine kinase inhibitor, disrupts BCR signaling and leads to the egress of tumor cells from the microenvironment. Although the on-target effects on CLL cells are well defined, the impact on the microenvironment is less well studied. We therefore sought to characterize the in vivo effects of ibrutinib on the tumor microenvironment. Patients received single-agent ibrutinib on an investigator-initiated phase II trial. Serial blood and tissue samples were collected pretreatment and during treatment. Changes in cytokine levels, cellular subsets, and microenvironmental interactions were assessed. Serum levels of key chemokines and inflammatory cytokines decreased significantly in patients on ibrutinib. Furthermore, ibrutinib treatment decreased circulating tumor cells and overall T-cell numbers. Most notably, a reduced frequency of the Th17 subset of CD4(+)T cells was observed concurrent with reduced expression of activation markers and PD-1 on T cells. Consistent with direct inhibition of T cells, ibrutinib inhibited Th17 differentiation of murine CD4(+)T cells in vitro Finally, in the bone marrow microenvironment, we found that ibrutinib disaggregated the interactions of macrophages and CLL cells, inhibited secretion of CXCL13, and decreased the chemoattraction of CLL cells. In conjunction with inhibition of BCR signaling, these changes in the tumor microenvironment likely contribute to the antitumor activity of ibrutinib and may impact the efficacy of immunotherapeutic strategies in patients with CLL. See related commentary by Bachireddy and Wu, p. 1547. ©2015 American Association for Cancer Research.

Advanced human-system interface design review guideline. Evaluation procedures and guidelines for human factors engineering reviews

Energy Technology Data Exchange (ETDEWEB)

O`Hara, J.M.; Brown, W.S. [Brookhaven National Lab., Upton, NY (United States); Baker, C.C.; Welch, D.L.; Granda, T.M.; Vingelis, P.J. [Carlow International Inc., Falls Church, VA (United States)

1994-07-01

Advanced control rooms will use advanced human-system interface (HSI) technologies that may have significant implications for plant safety in that they will affect the operator`s overall role in the system, the method of information presentation, and the ways in which operators interact with the system. The U.S. Nuclear Regulatory Commission (NRC) reviews the HSI aspects of control rooms to ensure that they are designed to good human factors engineering principles and that operator performance and reliability are appropriately supported to protect public health and safety. The principal guidance available to the NRC, however, was developed more than ten years ago, well before these technological changes. Accordingly, the human factors guidance needs to be updated to serve as the basis for NRC review of these advanced designs. The purpose of this project was to develop a general approach to advanced HSI review and the human factors guidelines to support. NRC safety reviews of advanced systems. This two-volume report provides the results of the project. Volume I describes the development of the Advanced HSI Design Review Guideline (DRG) including (1) its theoretical and technical foundation, (2) a general model for the review of advanced HSIs, (3) guideline development in both hard-copy and computer-based versions, and (4) the tests and evaluations performed to develop and validate the DRG. Volume I also includes a discussion of the gaps in available guidance and a methodology for addressing them. Volume 2 provides the guidelines to be used for advanced HSI review and the procedures for their use.

Advanced human-system interface design review guideline. Evaluation procedures and guidelines for human factors engineering reviews

International Nuclear Information System (INIS)

O'Hara, J.M.; Brown, W.S.; Baker, C.C.; Welch, D.L.; Granda, T.M.; Vingelis, P.J.

1994-07-01

Advanced control rooms will use advanced human-system interface (HSI) technologies that may have significant implications for plant safety in that they will affect the operator's overall role in the system, the method of information presentation, and the ways in which operators interact with the system. The U.S. Nuclear Regulatory Commission (NRC) reviews the HSI aspects of control rooms to ensure that they are designed to good human factors engineering principles and that operator performance and reliability are appropriately supported to protect public health and safety. The principal guidance available to the NRC, however, was developed more than ten years ago, well before these technological changes. Accordingly, the human factors guidance needs to be updated to serve as the basis for NRC review of these advanced designs. The purpose of this project was to develop a general approach to advanced HSI review and the human factors guidelines to support. NRC safety reviews of advanced systems. This two-volume report provides the results of the project. Volume I describes the development of the Advanced HSI Design Review Guideline (DRG) including (1) its theoretical and technical foundation, (2) a general model for the review of advanced HSIs, (3) guideline development in both hard-copy and computer-based versions, and (4) the tests and evaluations performed to develop and validate the DRG. Volume I also includes a discussion of the gaps in available guidance and a methodology for addressing them. Volume 2 provides the guidelines to be used for advanced HSI review and the procedures for their use

Household air pollution (HAP), microenvironment and child health: Strategies for mitigating HAP exposure in urban Rwanda

Science.gov (United States)

Das, Ipsita; Pedit, Joseph; Handa, Sudhanshu; Jagger, Pamela

2018-04-01

Exposure to household air pollution (HAP) from cooking and heating with solid fuels is a major risk factor for morbidity and mortality in sub-Saharan Africa. Children under five are particularly at risk for acute lower respiratory infection. We use baseline data from a randomized controlled trial evaluating a household energy intervention in Gisenyi, Rwanda to investigate the role of the microenvironment as a determinant of children’s HAP-related health symptoms. Our sample includes 529 households, with 694 children under five. We examine the association between likelihood of HAP-related health symptom prevalence and characteristics of the microenvironment including: dwelling and cooking area structure; distance to nearest road; and tree cover. We find that children residing in groups of enclosed dwellings, in households that cook indoors, and in households proximate to tree cover, are significantly more likely to experience symptoms of respiratory infection, illness with cough and difficulty breathing. On the other hand, children in households with cemented floors and ventilation holes in the cooking area, are significantly less likely to experience the same symptoms. Our findings suggest that in addition to promoting increased access to clean cooking technologies, there are important infrastructure and microenvironment-related interventions that mitigate HAP exposure.

Tissue engineering for human urethral reconstruction: systematic review of recent literature.

Science.gov (United States)

de Kemp, Vincent; de Graaf, Petra; Fledderus, Joost O; Ruud Bosch, J L H; de Kort, Laetitia M O

2015-01-01

Techniques to treat urethral stricture and hypospadias are restricted, as substitution of the unhealthy urethra with tissue from other origins (skin, bladder or buccal mucosa) has some limitations. Therefore, alternative sources of tissue for use in urethral reconstructions are considered, such as ex vivo engineered constructs. To review recent literature on tissue engineering for human urethral reconstruction. A search was made in the PubMed and Embase databases restricted to the last 25 years and the English language. A total of 45 articles were selected describing the use of tissue engineering in urethral reconstruction. The results are discussed in four groups: autologous cell cultures, matrices/scaffolds, cell-seeded scaffolds, and clinical results of urethral reconstructions using these materials. Different progenitor cells were used, isolated from either urine or adipose tissue, but slightly better results were obtained with in vitro expansion of urothelial cells from bladder washings, tissue biopsies from the bladder (urothelium) or the oral cavity (buccal mucosa). Compared with a synthetic scaffold, a biological scaffold has the advantage of bioactive extracellular matrix proteins on its surface. When applied clinically, a non-seeded matrix only seems suited for use as an onlay graft. When a tubularized substitution is the aim, a cell-seeded construct seems more beneficial. Considerable experience is available with tissue engineering of urethral tissue in vitro, produced with cells of different origin. Clinical and in vivo experiments show promising results.

Disruption of in vivo chronic lymphocytic leukemia tumor-microenvironment interactions by ibrutinib – findings from an investigator initiated phase 2 study

Science.gov (United States)

Niemann, Carsten U.; Herman, Sarah E. M.; Maric, Irina; Gomez-Rodriguez, Julio; Biancotto, Angelique; Chang, Betty Y.; Martyr, Sabrina; Stetler-Stevenson, Maryalice; Yuan, Constance; Calvo, Katherine R.; Braylan, Raul C.; Valdez, Janet; Lee, Yuh Shan; Wong, Deanna H.; Jones, Jade; Sun, Clare C. L.; Marti, Gerald E.; Farooqui, Mohammed Z.; Wiestner, Adrian

2016-01-01

Purpose Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental interactions for proliferation and survival that are at least partially mediated through B cell receptor (BCR) signaling. Ibrutinib, a Bruton’s tyrosine kinase inhibitor, disrupts BCR signaling and leads to the egress of tumor cells from the microenvironment. While the on-target effects on CLL cells are well defined, the impact on the microenvironment is less well studied. We therefore sought to characterize the in vivo effects of ibrutinib on the tumor microenvironment. Experimental Design Patients received single agent ibrutinib on an investigator-initiated phase 2 trial. Serial blood and tissue samples were collected pre-treatment and during treatment. Changes in cytokine levels, cellular subsets and microenvironmental interactions were assessed. Results Serum levels of key chemokines and inflammatory cytokines decreased significantly in patients on ibrutinib. Further, ibrutinib treatment decreased circulating tumor cells and overall T cell numbers. Most notably, a reduced frequency of the Th17 subset of CD4+ T cells was observed concurrent with reduced activation markers and expression of PD-1 on T cells. Consistent with direct inhibition of T cells, ibrutinib inhibited Th17 differentiation of murine CD4+ T cells in vitro. Lastly, in the bone marrow microenvironment, we found that ibrutinib disaggregated the interactions of macrophages and CLL cells, inhibited secretion of CXCL13 and decreased the chemoattraction of CLL cells. Conclusions In conjunction with inhibition of BCR signaling, these changes in the tumor microenvironment likely contribute to the anti-tumor activity of ibrutinib and may impact the efficacy of immunotherapeutic strategies in patients with CLL. PMID:26660519

The case for applying tissue engineering methodologies to instruct human organoid morphogenesis.

Science.gov (United States)

Marti-Figueroa, Carlos R; Ashton, Randolph S

2017-05-01

Three-dimensional organoids derived from human pluripotent stem cell (hPSC) derivatives have become widely used in vitro models for studying development and disease. Their ability to recapitulate facets of normal human development during in vitro morphogenesis produces tissue structures with unprecedented biomimicry. Current organoid derivation protocols primarily rely on spontaneous morphogenesis processes to occur within 3-D spherical cell aggregates with minimal to no exogenous control. This yields organoids containing microscale regions of biomimetic tissues, but at the macroscale (i.e. 100's of microns to millimeters), the organoids' morphology, cytoarchitecture, and cellular composition are non-biomimetic and variable. The current lack of control over in vitro organoid morphogenesis at the microscale induces aberrations at the macroscale, which impedes realization of the technology's potential to reproducibly form anatomically correct human tissue units that could serve as optimal human in vitro models and even transplants. Here, we review tissue engineering methodologies that could be used to develop powerful approaches for instructing multiscale, 3-D human organoid morphogenesis. Such technological mergers are critically needed to harness organoid morphogenesis as a tool for engineering functional human tissues with biomimetic anatomy and physiology. Human PSC-derived 3-D organoids are revolutionizing the biomedical sciences. They enable the study of development and disease within patient-specific genetic backgrounds and unprecedented biomimetic tissue microenvironments. However, their uncontrolled, spontaneous morphogenesis at the microscale yields inconsistences in macroscale organoid morphology, cytoarchitecture, and cellular composition that limits their standardization and application. Integration of tissue engineering methods with organoid derivation protocols could allow us to harness their potential by instructing standardized in vitro morphogenesis

Three-dimensional in vitro cancer models: a short review

International Nuclear Information System (INIS)

Wang, Chengyang; Sun, Wei; Tang, Zhenyu; Li, Lingsong; Zhao, Yu; Yao, Rui

2014-01-01

The re-creation of the tumor microenvironment including tumor–stromal interactions, cell–cell adhesion and cellular signaling is essential in cancer-related studies. Traditional two-dimensional (2D) cell culture and animal models have been proven to be valid in some areas of explaining cancerous cell behavior and interpreting hypotheses of possible mechanisms. However, a well-defined three-dimensional (3D) in vitro cancer model, which mimics tumor structures found in vivo and allows cell–cell and cell–matrix interactions, has gained strong interest for a wide variety of diagnostic and therapeutic applications. This communication attempts to provide a representative overview of applying 3D in vitro biological model systems for cancer related studies. The review compares and comments on the differences in using 2D models, animal models and 3D in vitro models for cancer research. Recent technologies to construct and develop 3D in vitro cancer models are summarized in aspects of modeling design, fabrication technique and potential application to biology, pathogenesis study and drug testing. With the help of advanced engineering techniques, the development of a novel complex 3D in vitro cancer model system will provide a better opportunity to understand crucial cancer mechanisms and to develop new clinical therapies. (topical review)

Tissue engineering and microRNAs: future perspectives in regenerative medicine.

Science.gov (United States)

Gori, Manuele; Trombetta, Marcella; Santini, Daniele; Rainer, Alberto

2015-01-01

Tissue engineering is a growing area of biomedical research, holding great promise for a broad range of potential applications in the field of regenerative medicine. In recent decades, multiple tissue engineering strategies have been adopted to mimic and improve specific biological functions of tissues and organs, including biomimetic materials, drug-releasing scaffolds, stem cells, and dynamic culture systems. MicroRNAs (miRNAs), noncoding small RNAs that negatively regulate the expression of downstream target mRNAs, are considered a novel class of molecular targets and therapeutics that may play an important role in tissue engineering. Herein, we highlight the latest achievements in regenerative medicine, focusing on the role of miRNAs as key modulators of gene expression, stem cell self-renewal, proliferation and differentiation, and eventually in driving cell fate decisions. Finally, we will discuss the contribution of miRNAs in regulating the rearrangement of the tissue microenvironment and angiogenesis, and the range of strategies for miRNA delivery into target cells and tissues. Manipulation of miRNAs is an alternative approach and an attractive strategy for controlling several aspects of tissue engineering, although some issues concerning their in vivo effects and optimal delivery methods still remain uncovered.

Preclinical Models in Chimeric Antigen Receptor-Engineered T-Cell Therapy.

Science.gov (United States)

Siegler, Elizabeth Louise; Wang, Pin

2018-05-01

Cancer immunotherapy has enormous potential in inducing long-term remission in cancer patients, and chimeric antigen receptor (CAR)-engineered T cells have been largely successful in treating hematological malignancies in the clinic. CAR-T therapy has not been as effective in treating solid tumors, in part due to the immunosuppressive tumor microenvironment. Additionally, CAR-T therapy can cause dangerous side effects, including off-tumor toxicity, cytokine release syndrome, and neurotoxicity. Animal models of CAR-T therapy often fail to predict such adverse events and frequently overestimate the efficacy of the treatment. Nearly all preclinical CAR-T studies have been performed in mice, including syngeneic, xenograft, transgenic, and humanized mouse models. Recently, a few studies have used primate models to mimic clinical side effects better. To date, no single model perfectly recapitulates the human immune system and tumor microenvironment, and some models have revealed CAR-T limitations that were contradicted or missed entirely in other models. Careful model selection based on the primary goals of the study is a crucial step in evaluating CAR-T treatment. Advancements are being made in preclinical models, with the ultimate objective of providing safer, more effective CAR-T therapy to patients.

Influence of microenvironment pH, humidity, and temperature on the stability of polymorphic and amorphous forms of clopidogrel bisulfate

DEFF Research Database (Denmark)

Raijada, Dhara K; Singh, Saranjit; Bansal, Arvind K

2010-01-01

The effect of microenvironment pH, humidity, and temperature was evaluated on the stability of polymorphic and amorphous forms of clopidogrel bisulfate, when present alone or in combinations. Oxalic acid and sodium carbonate were used as solid stressors to create acidic and alkaline p...... more degradation than the individual forms above critical relative humidity (85% RH). Similar higher degradation was observed between 75% RH and 85% RH in case of acid-stressed samples. In alkaline microenvironment, all the samples showed identical decomposition attributed to conversion of bisulfate...

Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review.

Science.gov (United States)

Chaudhari, Atul A; Vig, Komal; Baganizi, Dieudonné Radé; Sahu, Rajnish; Dixit, Saurabh; Dennis, Vida; Singh, Shree Ram; Pillai, Shreekumar R

2016-11-25

Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL), and poly-ethylene-glycol (PEG), etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts.

3D is not enough: Building up a cell instructive microenvironment for tumoral stroma microtissues.

Science.gov (United States)

Brancato, Virginia; Garziano, Alessandro; Gioiella, Filomena; Urciuolo, Francesco; Imparato, Giorgia; Panzetta, Valeria; Fusco, Sabato; Netti, Paolo A

2017-01-01

We fabricated three-dimensional microtissues with the aim to replicate in vitro the composition and the functionalities of the tumor microenvironment. By arranging either normal fibroblasts (NF) or cancer-activated fibroblasts (CAF) in two different three dimensional (3D) configurations, two kinds of micromodules were produced: spheroids and microtissues. Spheroids were obtained by means of the traditional cell aggregation technique resulting in a 3D model characterized by high cell density and low amount of extracellular proteins. The microtissues were obtained by culturing cells into porous gelatin microscaffolds. In this latter configuration, cells assembled an intricate network of collagen, fibronectin and hyaluronic acid. We investigated the biophysical properties of both 3D models in terms of cell growth, metabolic activity, texture and composition of the extracellular matrix (via histological analysis and multiphoton imaging) and cell mechanical properties (via Particle Tracking Microrheology). In the spheroid models such biophysical properties remained unchanged regardless to the cell type used. In contrast, normal-microtissues and cancer-activated-microtissues displayed marked differences. CAF-microtissues possessed higher proliferation rate, superior contraction capability, different micro-rheological properties and an extracellular matrix richer in collagen fibronectin and hyaluronic acid. At last, multiphoton investigation revealed differences in the collagen network architecture. Taken together, these results suggested that despite to cell spheroids, microtissues better recapitulate the important differences existing in vivo between normal and cancer-activated stroma representing a more suitable system to mimic in vitro the stromal element of the tumor tissues. This work concerns the engineering of tumor tissue in vitro. Tumor models serve as biological equivalent to study pathologic progression and to screen or validate the drugs efficacy. Tumor

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Directory of Open Access Journals (Sweden)

Alessandro Poggi

2016-11-01

Full Text Available The tumor microenvironment is a good target for therapy in solid tumors and hematological malignancies. Indeed, solid tumor cells’ growth and expansion can influence neighboring cells’ behavior, leading to a modulation of mesenchymal stromal cell (MSC activities and remodeling of extracellular matrix components. This leads to an altered microenvironment, where reparative mechanisms, in the presence of sub-acute inflammation, are not able to reconstitute healthy tissue. Carcinoma cells can undergo epithelial mesenchymal transition (EMT, a key step to generate metastasis; these mesenchymal-like cells display the functional behavior of MSC. Furthermore, MSC can support the survival and growth of leukemic cells within bone marrow participating in the leukemic cell niche. Notably, MSC can inhibit the anti-tumor immune response through either carcinoma-associated fibroblasts or bone marrow stromal cells. Experimental data have indicated their relevance in regulating cytolytic effector lymphocytes of the innate and adaptive arms of the immune system. Herein, we will discuss some of the evidence in hematological malignancies and solid tumors. In particular, we will focus our attention on the means by which it is conceivable to inhibit MSC-mediated immune suppression and trigger anti-tumor innate immunity.

Ambulatory Antibiotic Stewardship through a Human Factors Engineering Approach: A Systematic Review.

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Keller, Sara C; Tamma, Pranita D; Cosgrove, Sara E; Miller, Melissa A; Sateia, Heather; Szymczak, Julie; Gurses, Ayse P; Linder, Jeffrey A

2018-01-01

In the United States, most antibiotics are prescribed in ambulatory settings. Human factors engineering, which explores interactions between people and the place where they work, has successfully improved quality of care. However, human factors engineering models have not been explored to frame what is known about ambulatory antibiotic stewardship (AS) interventions and barriers and facilitators to their implementation. We conducted a systematic review and searched OVID MEDLINE, Embase, Scopus, Web of Science, and CINAHL to identify controlled interventions and qualitative studies of ambulatory AS and determine whether and how they incorporated principles from a human factors engineering model, the Systems Engineering Initiative for Patient Safety 2.0 model. This model describes how a work system (ambulatory clinic) contributes to a process (antibiotic prescribing) that leads to outcomes. The work system consists of 5 components, tools and technology, organization, person, tasks, and environment, within an external environment. Of 1,288 abstracts initially identified, 42 quantitative studies and 17 qualitative studies met inclusion criteria. Effective interventions focused on tools and technology (eg, clinical decision support and point-of-care testing), the person (eg, clinician education), organization (eg, audit and feedback and academic detailing), tasks (eg, delayed antibiotic prescribing), the environment (eg, commitment posters), and the external environment (media campaigns). Studies have not focused on clinic-wide approaches to AS. A human factors engineering approach suggests that investigating the role of the clinic's processes or physical layout or external pressures' role in antibiotic prescribing may be a promising way to improve ambulatory AS. © Copyright 2018 by the American Board of Family Medicine.

Impacts of exhalation flow on the microenvironment around the human body under different room temperatures

Science.gov (United States)

Jafari, Mohammad Javad; Gharari, Noradin; Azari, Mansour Rezazade; Ashrafi, Khosro

2018-04-01

Exhalation flow and room temperature can have a considerable effect on the microenvironment in the vicinity of human body. In this study, impacts of exhalation flow and room temperature on the microenvironment around a human body were investigated using a numerical simulation. For this purpose, a computational fluid dynamic program was applied to study thermal plume around a sitting human body at different room temperatures of a calm indoor room by considering the exhalation flow. The simulation was supported by some experimental measurements. Six different room temperatures (18 to 28 °C) with two nose exhalation modes (exhalation and non-exhalation) were investigated. Overhead and breathing zone velocities and temperatures were simulated in different scenarios. This study finds out that the exhalation through the nose has a significant impact on both quantitative and qualitative features of the human microenvironment in different room temperatures. At a given temperature, the exhalation through the nose can change the location and size of maximum velocity at the top of the head. In the breathing zone, the effect of exhalation through the nose on velocity and temperature distribution was pronounced for the point close to mouth. Also, the exhalation through the nose strongly influences the thermal boundary layer on the breathing zone while it only minimally influences the convective boundary layer on the breathing zone. Overall results demonstrate that it is important to take the exhalation flow into consideration in all areas, especially at a quiescent flow condition with low temperature.

The Bioelectric Code: Reprogramming Cancer and Aging From the Interface of Mechanical and Chemical Microenvironments

Directory of Open Access Journals (Sweden)

Brian B. Silver

2018-03-01

Full Text Available Cancer is a complex, heterogeneous group of diseases that can develop through many routes. Broad treatments such as chemotherapy destroy healthy cells in addition to cancerous ones, but more refined strategies that target specific pathways are usually only effective for a limited number of cancer types. This is largely due to the multitude of physiological variables that differ between cells and their surroundings. It is therefore important to understand how nature coordinates these variables into concerted regulation of growth at the tissue scale. The cellular microenvironment might then be manipulated to drive cells toward a desired outcome at the tissue level. One unexpected parameter, cellular membrane voltage (Vm, has been documented to exert control over cellular behavior both in culture and in vivo. Manipulating this fundamental cellular property influences a remarkable array of organism-wide patterning events, producing striking outcomes in both tumorigenesis as well as regeneration. These studies suggest that Vm is not only a key intrinsic cellular property, but also an integral part of the microenvironment that acts in both space and time to guide cellular behavior. As a result, there is considerable interest in manipulating Vm both to treat cancer as well as to regenerate organs damaged or deteriorated during aging. However, such manipulations have produced conflicting outcomes experimentally, which poses a substantial barrier to understanding the fundamentals of bioelectrical reprogramming. Here, we summarize these inconsistencies and discuss how the mechanical microenvironment may impact bioelectric regulation.

Absorbed dose in fibrotic microenvironment models employing Monte Carlo simulation

International Nuclear Information System (INIS)

Zambrano Ramírez, O.D.; Rojas Calderón, E.L.; Azorín Vega, E.P.; Ferro Flores, G.; Martínez Caballero, E.

2015-01-01

The presence or absence of fibrosis and yet more, the multimeric and multivalent nature of the radiopharmaceutical have recently been reported to have an effect on the radiation absorbed dose in tumor microenvironment models. Fibroblast and myofibroblast cells produce the extracellular matrix by the secretion of proteins which provide structural and biochemical support to cells. The reactive and reparative mechanisms triggered during the inflammatory process causes the production and deposition of extracellular matrix proteins, the abnormal excessive growth of the connective tissue leads to fibrosis. In this work, microenvironment (either not fibrotic or fibrotic) models composed of seven spheres representing cancer cells of 10 μm in diameter each with a 5 μm diameter inner sphere (cell nucleus) were created in two distinct radiation transport codes (PENELOPE and MCNP). The purpose of creating these models was to determine the radiation absorbed dose in the nucleus of cancer cells, based on previously reported radiopharmaceutical retain (by HeLa cells) percentages of the 177 Lu-Tyr 3 -octreotate (monomeric) and 177 Lu-Tyr 3 -octreotate-AuNP (multimeric) radiopharmaceuticals. A comparison in the results between the PENELOPE and MCNP was done. We found a good agreement in the results of the codes. The percent difference between the increase percentages of the absorbed dose in the not fibrotic model with respect to the fibrotic model of the codes PENELOPE and MCNP was found to be under 1% for both radiopharmaceuticals. (authors)

Report of the evaluation by the Ad Hoc Review Committee on Computational Science and Engineering. Result evaluation in fiscal year 2000

International Nuclear Information System (INIS)

2001-06-01

The Research Evaluation Committee, which consisted of 14 members from outside of the Japan Atomic Energy Research Institute (JAERI), set up an Ad Hoc Review Committee on Computational Science and Engineering in accordance with the 'Fundamental Guideline for the Evaluation of Research and Development (R and D) at JAERI' and its subsidiary regulations in order to evaluate the R and D accomplishments achieved for five years from Fiscal Year 1995 to Fiscal Year 1999 at Center for Promotion of Computational Science and Engineering of JAERI. The Ad Hoc Review Committee consisted of seven specialists from outside of JAERI. The Ad Hoc Review Committee conducted its activities from December 2000 to March 2001. The evaluation was performed on the basis of the materials submitted in advance and of the oral presentations made at the Ad Hoc Review Committee meeting which was held on December 27, 2000, in line with the items, viewpoints, and criteria for the evaluation specified by the Research Evaluation Committee. The result of the evaluation by the Ad Hoc Review Committee was submitted to the Research Evaluation Committee, and was judged to be appropriate at its meeting held on March 16, 2001. This report describes the result of the evaluation by the Ad Hoc Review Committee on Computational Science and Engineering. (author)

Spectroscopic evidence for an engineered, catalytically active Trp radical that creates the unique reactivity of lignin peroxidase.

Science.gov (United States)

Smith, Andrew T; Doyle, Wendy A; Dorlet, Pierre; Ivancich, Anabella

2009-09-22

The surface oxidation site (Trp-171) in lignin peroxidase (LiP) required for the reaction with veratryl alcohol a high-redox-potential (1.4 V) substrate, was engineered into Coprinus cinereus peroxidase (CiP) by introducing a Trp residue into a heme peroxidase that has similar protein fold but lacks this activity. To create the catalytic activity toward veratryl alcohol in CiP, it was necessary to reproduce the Trp site and its negatively charged microenvironment by means of a triple mutation. The resulting D179W+R258E+R272D variant was characterized by multifrequency EPR spectroscopy. The spectra unequivocally showed that a new Trp radical [g values of g(x) = 2.0035(5), g(y) = 2.0027(5), and g(z) = 2.0022(1)] was formed after the [Fe(IV)=O Por(*+)] intermediate, as a result of intramolecular electron transfer between Trp-179 and the porphyrin. Also, the EPR characterization crucially showed that [Fe(IV)=O Trp-179(*)] was the reactive intermediate with veratryl alcohol. Accordingly, our work shows that it is necessary to take into account the physicochemical properties of the radical, fine-tuned by the microenvironment, as well as those of the preceding [Fe(IV)=O Por(*+)] intermediate to engineer a catalytically competent Trp site for a given substrate. Manipulation of the microenvironment of the Trp-171 site in LiP allowed the detection by EPR spectroscopy of the Trp-171(*), for which direct evidence has been missing so far. Our work also highlights the role of Trp residues as tunable redox-active cofactors for enzyme catalysis in the context of peroxidases with a unique reactivity toward recalcitrant substrates that require oxidation potentials not realized at the heme site.

Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease

Science.gov (United States)

Cruz, Nelly M.; Song, Xuewen; Czerniecki, Stefan M.; Gulieva, Ramila E.; Churchill, Angela J.; Kim, Yong Kyun; Winston, Kosuke; Tran, Linh M.; Diaz, Marco A.; Fu, Hongxia; Finn, Laura S.; Pei, York; Himmelfarb, Jonathan; Freedman, Benjamin S.

2017-11-01

Polycystic kidney disease (PKD) is a life-threatening disorder, commonly caused by defects in polycystin-1 (PC1) or polycystin-2 (PC2), in which tubular epithelia form fluid-filled cysts. A major barrier to understanding PKD is the absence of human cellular models that accurately and efficiently recapitulate cystogenesis. Previously, we have generated a genetic model of PKD using human pluripotent stem cells and derived kidney organoids. Here we show that systematic substitution of physical components can dramatically increase or decrease cyst formation, unveiling a critical role for microenvironment in PKD. Removal of adherent cues increases cystogenesis 10-fold, producing cysts phenotypically resembling PKD that expand massively to 1-centimetre diameters. Removal of stroma enables outgrowth of PKD cell lines, which exhibit defects in PC1 expression and collagen compaction. Cyclic adenosine monophosphate (cAMP), when added, induces cysts in both PKD organoids and controls. These biomaterials establish a highly efficient model of PKD cystogenesis that directly implicates the microenvironment at the earliest stages of the disease.

The species origin of the cellular microenvironment influences markers of beta cell fate and function in EndoC-βH1 cells.

Science.gov (United States)

Jeffery, N; Richardson, S; Beall, C; Harries, L W

2017-12-15

Interaction between islet cell subtypes and the extracellular matrix influences beta-cell function in mammals. The tissue architecture of rodent islets is very different to that of human islets; cell-to-cell communication and interaction with the extracellular matrix may vary between species. In this work, we have compared the responses of the human EndoC-βH1 cell line to non-human and human-derived growth matrices in terms of growth morphology, gene expression and glucose-stimulated insulin secretion (GSIS). EndoC-βH1 cells demonstrated a greater tendency to form cell clusters when cultured in a human microenvironment and exhibited reduced alpha cell markers at the mRNA level; mean expression difference - 0.23 and - 0.51; p = 0.009 and 0.002 for the Aristaless-related homeobox (ARX) and Glucagon (GCG) genes respectively. No differences were noted in the protein expression of mature beta cell markers such as Pdx1 and NeuroD1 were noted in EndoC-βH1 cells grown in a human microenvironment but cells were however more sensitive to glucose (4.3-fold increase in insulin secretion following glucose challenge compared with a 1.9-fold increase in cells grown in a non-human microenvironment; p = 0.0003). Our data suggests that the tissue origin of the cellular microenvironment has effects on the function of EndoC-βH1 cells in vitro, and the use of a more human-like culture microenvironment may bring benefits in terms of increased physiological relevance. Copyright © 2017 Elsevier Inc. All rights reserved.

How Engineers Negotiate Domain Boundaries in a Complex, Interdisciplinary Engineering Project

Science.gov (United States)

Panther, Grace; Montfort, Devlin; Pirtle, Zachary

2017-01-01

Engineering educators have an essential role in preparing engineers to work in a complex, interdisciplinary workforce. While much engineering education focuses on teaching students to develop disciplinary expertise in specific engineering domains, there is a strong need to teach engineers about the knowledge that they develop or use in their work (Bucciarelli 1994, Allenby Sarewitz, 2011; Frodeman, 2013). The purpose of this research is to gain a better understanding of the knowledge systems of practicing engineers through observations of their practices such that the insights learned can guide future education efforts. Using an example from a complex and interdisciplinary engineering project, this paper presents a case study overviewing the types of epistemological (or knowledge-acquiring or using) complexities that engineers navigate. Specifically, we looked at a discussion of the thermal design of a CubeSat that occurred during an engineering review at NASA. We analyzed the review using a framework that we call 'peak events', or pointed discussions between reviewers, project engineers, and managers. We examined the dialog within peak events to identify the ways that knowledge was brought to bear, highlighting discussions of uncertainty and the boundaries of knowledge claims. We focus on one example discussion surrounding the thermal design of the CubeSat, which provides a particularly thorough example of a knowledge system since the engineers present explained, justified, negotiated, and defended knowledge within a social setting. Engineering students do not get much practice or instruction in explicitly negotiating knowledge systems and epistemic standards in this way. We highlight issues that should matter to engineering educators, such as the need to discuss what level of uncertainty is sufficient and the need to negotiate boundaries of system responsibility. Although this analysis is limited to a single discussion or 'peak event', our case shows that this

The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment

Directory of Open Access Journals (Sweden)

Delia Nelson

2014-01-01

Full Text Available Most anticancer therapies including immunotherapies are given systemically; yet therapies given directly into tumors may be more effective, particularly those that overcome natural suppressive factors in the tumor microenvironment. The “Trojan Horse” approach of intratumoural delivery aims to promote immune-mediated destruction by inducing microenvironmental changes within the tumour at the same time as avoiding the systemic toxicity that is often associated with more “full frontal” treatments such as transfer of large numbers of laboratory-expanded tumor-specific cytotoxic T lymphocytes or large intravenous doses of cytokine. Numerous studies have demonstrated that intratumoural therapy has the capacity to minimizing local suppression, inducing sufficient “dangerous” tumor cell death to cross-prime strong immune responses, and rending tumor blood vessels amenable to immune cell traffic to induce effector cell changes in secondary lymphoid organs. However, the key to its success is the design of a sound rational approach based on evidence. There is compelling preclinical data for local immunotherapy approaches in tumor immunology. This review summarises how immune events within a tumour can be modified by local approaches, how this can affect systemic antitumor immunity such that distal sites are attacked, and what approaches have been proven most successful so far in animals and patients.

Traction force microscopy of engineered cardiac tissues.

Science.gov (United States)

Pasqualini, Francesco Silvio; Agarwal, Ashutosh; O'Connor, Blakely Bussie; Liu, Qihan; Sheehy, Sean P; Parker, Kevin Kit

2018-01-01

Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tissue-level preparations. Using this system, we investigated the relationship between contractile proficiency and metabolism in neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa) cardiac microenvironments. We found that tissues engineered on the softest gels generated the least amount of stress and had the smallest work output. Conversely, cardiomyocytes in tissues engineered on healthy- and disease-mimicking gels generated significantly higher stresses, with the maximal contractile work measured in NRVM engineered on gels of normal stiffness. Interestingly, although tissues on soft gels exhibited poor stress generation and work production, their basal metabolic respiration rate was significantly more elevated than in other groups, suggesting a highly ineffective coupling between energy production and contractile work output. Our novel platform can thus be utilized to quantitatively assess the mechanotransduction pathways that initiate tissue-level structural and functional remodeling in response to substrate stiffness.

Nano scaffolds and stem cell therapy in liver tissue engineering

Science.gov (United States)

Montaser, Laila M.; Fawzy, Sherin M.

2015-08-01

Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

Design properties of hydrogel tissue-engineering scaffolds

Science.gov (United States)

Zhu, Junmin; Marchant, Roger E

2011-01-01

This article summarizes the recent progress in the design and synthesis of hydrogels as tissue-engineering scaffolds. Hydrogels are attractive scaffolding materials owing to their highly swollen network structure, ability to encapsulate cells and bioactive molecules, and efficient mass transfer. Various polymers, including natural, synthetic and natural/synthetic hybrid polymers, have been used to make hydrogels via chemical or physical crosslinking. Recently, bioactive synthetic hydrogels have emerged as promising scaffolds because they can provide molecularly tailored biofunctions and adjustable mechanical properties, as well as an extracellular matrix-like microenvironment for cell growth and tissue formation. This article addresses various strategies that have been explored to design synthetic hydrogels with extracellular matrix-mimetic bioactive properties, such as cell adhesion, proteolytic degradation and growth factor-binding. PMID:22026626

Engine Tune-Up Service. Unit 3: Primary Circuit. Review Exercise Book. Automotive Mechanics Curriculum.

Science.gov (United States)

Bacon, E. Miles

This book of pretests and review exercises is designed to accompany the Engine Tune-Up Service Student Guide for Unit 3, Primary Circuit, available separately as CE 031 211. Focus of the exercises and pretests is testing the primary ignition circuit. Pretests and performance checklists are provided for each of the eight performance objectives…

Engine Tune-up Service. Unit 2: Charging System. Review Exercise Book. Automotive Mechanics Curriculum.

Science.gov (United States)

Richardson, Roger L.; Bacon, E. Miles

This book of pretests and review exercises is designed to accompany the Engine Tune-Up Service Student Guide for Unit 2, Charging System, available separately as CE 031 208. Focus of the exercises and pretests is testing the charging system. Pretests and performance checklists are provided for each of the three performance objectives contained in…

Engine Tune-up Service. Unit 4: Secondary Circuit. Review Exercise Book. Automotive Mechanics Curriculum.

Science.gov (United States)

Bacon, E. Miles

This book of pretests and review exercises is designed to accompany the Engine Tune-Up Service Student Guide for Unit 4, Secondary Circuit, available separately as CE 031 214. Focus of the exercises and pretests is testing and servicing the secondary ignition circuit. Pretests and performance checklists are provided for each of the seven…

Genome scale engineering techniques for metabolic engineering.

Science.gov (United States)

Liu, Rongming; Bassalo, Marcelo C; Zeitoun, Ramsey I; Gill, Ryan T

2015-11-01

Metabolic engineering has expanded from a focus on designs requiring a small number of genetic modifications to increasingly complex designs driven by advances in genome-scale engineering technologies. Metabolic engineering has been generally defined by the use of iterative cycles of rational genome modifications, strain analysis and characterization, and a synthesis step that fuels additional hypothesis generation. This cycle mirrors the Design-Build-Test-Learn cycle followed throughout various engineering fields that has recently become a defining aspect of synthetic biology. This review will attempt to summarize recent genome-scale design, build, test, and learn technologies and relate their use to a range of metabolic engineering applications. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Magnetic Resonance Spectroscopic Imaging of Tumor Metabolic Markers for Cancer Diagnosis, Metabolic Phenotyping, and Characterization of Tumor Microenvironment

Directory of Open Access Journals (Sweden)

Qiuhong He

2004-01-01

Full Text Available Cancer cells display heterogeneous genetic characteristics, depending on the tumor dynamic microenvironment. Abnormal tumor vasculature and poor tissue oxygenation generate a fraction of hypoxic tumor cells that have selective advantages in metastasis and invasion and often resist chemo- and radiation therapies. The genetic alterations acquired by tumors modify their biochemical pathways, which results in abnormal tumor metabolism. An elevation in glycolysis known as the “Warburg effect” and changes in lipid synthesis and oxidation occur. Magnetic resonance spectroscopy (MRS has been used to study tumor metabolism in preclinical animal models and in clinical research on human breast, brain, and prostate cancers. This technique can identify specific genetic and metabolic changes that occur in malignant tumors. Therefore, the metabolic markers, detectable by MRS, not only provide information on biochemical changes but also define different metabolic tumor phenotypes. When combined with the contrast-enhanced Magnetic Resonance Imaging (MRI, which has a high sensitivity for cancer diagnosis, in vivo magnetic resonance spectroscopic imaging (MRSI improves the diagnostic specificity of malignant human cancers and is becoming an important clinical tool for cancer management and care. This article reviews the MRSI techniques as molecular imaging methods to detect and quantify metabolic changes in various tumor tissue types, especially in extracranial tumor tissues that contain high concentrations of fat. MRI/MRSI methods have been used to characterize tumor microenvironments in terms of blood volume and vessel permeability. Measurements of tissue oxygenation and glycolytic rates by MRS also are described to illustrate the capability of the MR technology in probing molecular information non-invasively in tumor tissues and its important potential for studying molecular mechanisms of human cancers in physiological conditions.

Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent for detecting acidic tumor microenvironments.

Science.gov (United States)

Nwe, Kido; Huang, Ching-Hui; Tsourkas, Andrew

2013-10-24

Neoplastic lesions can create a hostile tumor microenvironment with low extracellular pH. It is commonly believed that these conditions can contribute to tumor progression as well as resistance to therapy. We report the development and characterization of a pH-responsive magnetic resonance imaging contrast agent for imaging the acidic tumor microenvironment. The preparation included the conjugation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid 1-(2,5-dioxo-1-pyrrolidinyl) ester (DOTA-NHS) to the surface of a water-soluble glycol chitosan (GC) polymer, which contains pH-titrable primary amines, followed by gadolinium complexation (GC-NH2-GdDOTA). GC-NH2-GdDOTA had a chelate-to-polymer ratio of approximately1:24 and a molar relaxivity of 9.1 mM(-1) s(-1). GC-NH2-GdDOTA demonstrated pH-dependent cellular association in vitro compared to the control. It also generated a 2.4-fold enhancement in signal in tumor-bearing mice 2 h postinjection. These findings suggest that glycol chitosan coupled with contrast agents can provide important diagnostic information about the tumor microenvironment.

COBRA System Engineering Processes to Achieve SLI Strategic Goals

Science.gov (United States)

Ballard, Richard O.

2003-01-01

The COBRA Prototype Main Engine Development Project was an endeavor conducted as a joint venture between Pratt & Whitney and Aerojet to conduct risk reduction in LOX/LH2 main engine technology for the NASA Space Launch Initiative (SLI). During the seventeen months of the project (April 2001 to September 2002), approximately seventy reviews were conducted, beginning with the Engine Systems Requirements Review (SRR) and ending with the Engine Systems Interim Design Review (IDR). This paper discusses some of the system engineering practices used to support the reviews and the overall engine development effort.

Smart Polymeric Hydrogels for Cartilage Tissue Engineering: A Review on the Chemistry and Biological Functions.

Science.gov (United States)

Eslahi, Niloofar; Abdorahim, Marjan; Simchi, Abdolreza

2016-11-14

Stimuli responsive hydrogels (SRHs) are attractive bioscaffolds for tissue engineering. The structural similarity of SRHs to the extracellular matrix (ECM) of many tissues offers great advantages for a minimally invasive tissue repair. Among various potential applications of SRHs, cartilage regeneration has attracted significant attention. The repair of cartilage damage is challenging in orthopedics owing to its low repair capacity. Recent advances include development of injectable hydrogels to minimize invasive surgery with nanostructured features and rapid stimuli-responsive characteristics. Nanostructured SRHs with more structural similarity to natural ECM up-regulate cell-material interactions for faster tissue repair and more controlled stimuli-response to environmental changes. This review highlights most recent advances in the development of nanostructured or smart hydrogels for cartilage tissue engineering. Different types of stimuli-responsive hydrogels are introduced and their fabrication processes through physicochemical procedures are reported. The applications and characteristics of natural and synthetic polymers used in SRHs are also reviewed with an outline on clinical considerations and challenges.

The Fantastic Voyage of the Trypanosome: A Protean Micromachine Perfected during 500 Million Years of Engineering

Directory of Open Access Journals (Sweden)

Timothy Krüger

2018-02-01

Full Text Available The human body is constantly attacked by pathogens. Various lines of defence have evolved, among which the immune system is principal. In contrast to most pathogens, the African trypanosomes thrive freely in the blood circulation, where they escape immune destruction by antigenic variation and incessant motility. These unicellular parasites are flagellate microswimmers that also withstand the harsh mechanical forces prevailing in the bloodstream. They undergo complex developmental cycles in the bloodstream and organs of the mammalian host, as well as the disease-transmitting tsetse fly. Each life cycle stage has been shaped by evolution for manoeuvring in distinct microenvironments. Here, we introduce trypanosomes as blueprints for nature-inspired design of trypanobots, micromachines that, in the future, could explore the human body without affecting its physiology. We review cell biological and biophysical aspects of trypanosome motion. While this could provide a basis for the engineering of microbots, their actuation and control still appear more like fiction than science. Here, we discuss potentials and challenges of trypanosome-inspired microswimmer robots.

Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review

Directory of Open Access Journals (Sweden)

Atul A. Chaudhari

2016-11-01

Full Text Available Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL, and poly-ethylene-glycol (PEG, etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts.

Numerical simulation of the flow field and fuel sprays in an IC engine

Science.gov (United States)

Nguyen, H. L.; Schock, H. J.; Ramos, J. I.; Carpenter, M. H.; Stegeman, J. D.

1987-01-01

A two-dimensional model for axisymmetric piston-cylinder configurations is developed to study the flow field in two-stroke direct-injection Diesel engines under motored conditions. The model accounts for turbulence by a two-equation model for the turbulence kinetic energy and its rate of dissipation. A discrete droplet model is used to simulate the fuel spray, and the effects of the gas phase turbulence on the droplets is considered. It is shown that a fluctuating velocity can be added to the mean droplet velocity every time step if the step is small enough. Good agreement with experimental data is found for a range of ambient pressures in Diesel engine-type microenvironments. The effects of the intake swirl angle in the spray penetration, vaporization, and mixing in a uniflow-scavenged two-stroke Diesel engine are analyzed. It is found that the swirl increases the gas phase turbulence levels and the rates of vaporization.

Knee Ligament Injury and the Clinical Application of Tissue Engineering Techniques: A Systematic Review.

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Riley, Thomas C; Mafi, Reza; Mafi, Pouya; Khan, Wasim S

2018-02-23

The incidence of knee ligament injury is increasing and represents a significant cost to healthcare providers. Current interventions include tissue grafts, suture repair and non-surgical management. These techniques have demonstrated good patient outcomes but have been associated graft rejection, infection, long term immobilization and reduced joint function. The limitations of traditional management strategies have prompted research into tissue engineering of knee ligaments. This paper aims to evaluate whether tissue engineering of knee ligaments offers a viable alternative in the clinical management of knee ligament injuries. A search of existing literature was performed using OVID Medline, Embase, AMED, PubMed and Google Scholar, and a manual review of citations identified within these papers. Silk, polymer and extracellular matrix based scaffolds can all improve graft healing and collagen production. Fibroblasts and stem cells demonstrate compatibility with scaffolds, and have been shown to increase organized collagen production. These effects can be augmented using growth factors and extracellular matrix derivatives. Animal studies have shown tissue engineered ligaments can provide the biomechanical characteristics required for effective treatment of knee ligament injuries. There is a growing clinical demand for a tissue engineered alternative to traditional management strategies. Currently, there is limited consensus regarding material selection for use in tissue engineered ligaments. Further research is required to optimize tissue engineered ligament production before clinical application. Controlled clinical trials comparing the use of tissue engineered ligaments and traditional management in patients with knee ligament injury could determine whether they can provide a cost-effective alternative. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Updating Human Factors Engineering Guidelines for Conducting Safety Reviews of Nuclear Power Plants

International Nuclear Information System (INIS)

O'Hara, J.M.; Higgins, J.; Fleger, Stephen

2011-01-01

The U.S. Nuclear Regulatory Commission (NRC) reviews the human factors engineering (HFE) programs of applicants for nuclear power plant construction permits, operating licenses, standard design certifications, and combined operating licenses. The purpose of these safety reviews is to help ensure that personnel performance and reliability are appropriately supported. Detailed design review procedures and guidance for the evaluations is provided in three key documents: the Standard Review Plan (NUREG-0800), the HFE Program Review Model (NUREG-0711), and the Human-System Interface Design Review Guidelines (NUREG-0700). These documents were last revised in 2007, 2004 and 2002, respectively. The NRC is committed to the periodic update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool. To this end, the NRC is updating its guidance to stay current with recent research on human performance, advances in HFE methods and tools, and new technology being employed in plant and control room design. This paper describes the role of HFE guidelines in the safety review process and the content of the key HFE guidelines used. Then we will present the methodology used to develop HFE guidance and update these documents, and describe the current status of the update program.

Engineering Changes in Product Design - A Review

Science.gov (United States)

Karthik, K.; Janardhan Reddy, K., Dr

2016-09-01

Changes are fundamental to product development. Engineering changes are unavoidable and can arise at any phase of the product life cycle. The consideration of market requirements, customer/user feedbacks, manufacturing constraints, design innovations etc., turning them into viable products can be accomplished when product change is managed properly. In the early design cycle, informal changes are accepted. However, changes become formal when its complexity and cost increases, and as product matures. To maximize the market shares, manufacturers have to effectively and efficiently manage engineering changes by means of Configuration Control. The paper gives a broad overview about ‘Engineering Change Management’ (ECM) through configuration management and its implications in product design. The aim is to give an idea and understanding about the engineering changes in product design scenario to the new researchers. This paper elaborates the significant aspect of managing the engineering changes and the importance of ECM in a product life cycle.

The role of laminins in cartilaginous tissues: from development to regeneration.

Science.gov (United States)

Sun, Y; Wang, T L; Toh, W S; Pei, M

2017-07-21

As a key molecule of the extracellular matrix, laminin provides a delicate microenvironment for cell functions. Recent findings suggest that laminins expressed by cartilage-forming cells (chondrocytes, progenitor cells and stem cells) could promote chondrogenesis. However, few papers outline the effect of laminins on providing a favorable matrix microenvironment for cartilage regeneration. In this review, we delineated the expression of laminins in hyaline cartilage, fibrocartilage and cartilage-like tissue (nucleus pulposus) throughout several developmental stages. We also examined the effect of laminins on the biological activities of chondrocytes, including adhesion, migration and survival. Furthermore, we scrutinized the potential influence of various laminin isoforms on cartilage-forming cells' proliferation and chondrogenic differentiation. With this information, we hope to facilitate the understanding of the spatial and temporal interactions between cartilage-forming cells and laminin microenvironment to eventually advance cell-based cartilage engineering and regeneration.

Microenvironment around tumors and their radiation sensitivity. The possibility of molecular target for radiation sensitization

Energy Technology Data Exchange (ETDEWEB)

Akimoto, Tetsuo; Ishikawa, Hitoshi [Gunma Univ., Maebashi (Japan). School of Medicine; Mitsuhashi, Norio [Tokyo Women' s Medical Coll. (Japan)

2001-12-01

There have been scarce studies concerning the effect of microenvironment around tumors on their radiation sensitivity and this review describes the influence of environmental factors of cell adhesion, growth factors, cytokines, hypoxia and angiogenesis on the sensitivity and response to radiation and on the signal transduction to consider the possibility of molecular target for radiation sensitization. Cell-cell adhesion and cell-matrix interaction in response to radiation may have a role in inducing apoptotic process like anti-apoptotic or pro-apoptotic one. Growth factors and cytokines can affect the tumor response to radiation in more extent than p53 gene status since apoptosis induction is not always an indication of radiation sensitivity in many tumors clinically encountered. Radiation sensitivity is low in tumor cells under hypoxic conditions and it is important to know the relationship between those hypoxic cell response and angiogenesis by factors like HIF (hypoxia-inducible factor)-1. Molecular targets for radiation sensitization are now under development and both basic and clinical studies are important for future application of those sensitizing agents for the radiotherapy of tumors. (K.H.)

Microenvironment around tumors and their radiation sensitivity. The possibility of molecular target for radiation sensitization

International Nuclear Information System (INIS)

Akimoto, Tetsuo; Ishikawa, Hitoshi

2001-01-01

There have been scarce studies concerning the effect of microenvironment around tumors on their radiation sensitivity and this review describes the influence of environmental factors of cell adhesion, growth factors, cytokines, hypoxia and angiogenesis on the sensitivity and response to radiation and on the signal transduction to consider the possibility of molecular target for radiation sensitization. Cell-cell adhesion and cell-matrix interaction in response to radiation may have a role in inducing apoptotic process like anti-apoptotic or pro-apoptotic one. Growth factors and cytokines can affect the tumor response to radiation in more extent than p53 gene status since apoptosis induction is not always an indication of radiation sensitivity in many tumors clinically encountered. Radiation sensitivity is low in tumor cells under hypoxic conditions and it is important to know the relationship between those hypoxic cell response and angiogenesis by factors like HIF (hypoxia-inducible factor)-1. Molecular targets for radiation sensitization are now under development and both basic and clinical studies are important for future application of those sensitizing agents for the radiotherapy of tumors. (K.H.)

Decreased decorin expression in the tumor microenvironment

International Nuclear Information System (INIS)

Bozoky, Benedek; Savchenko, Andrii; Guven, Hayrettin; Ponten, Fredrik; Klein, George; Szekely, Laszlo

2014-01-01

Decorin is a small leucine-rich proteoglycan, synthesized and deposited by fibroblasts in the stroma where it binds to collagen I. It sequesters several growth factors and antagonizes numerous members of the receptor tyrosine kinase family. In experimental murine systems, it acted as a potent tumor suppressor. Examining the Human Protein Atlas online database of immunostained tissue samples we have surveyed decorin expression in silico in several different tumor types, comparing them with corresponding normal tissues. We found that decorin is abundantly secreted and deposited in normal connective tissue but its expression is consistently decreased in the tumor microenvironment. We developed a software to quantitate the difference in expression. The presence of two closely related proteoglycans in the newly formed tumor stroma indicated that the decreased decorin expression was not caused by the delay in proteoglycan deposition in the newly formed connective tissue surrounding the tumor

Software Engineering and Knowledge Engineering Theory and Practice Volume 2

CERN Document Server

2012-01-01

The volume includes a set of selected papers extended and revised from the I2009 Pacific-Asia Conference on Knowledge Engineering and Software Engineering (KESE 2009) was held on December 19~ 20, 2009, Shenzhen, China.   Volume 2 is to provide a forum for researchers, educators, engineers, and government officials involved in the general areas of Knowledge Engineering and Communication Technology to disseminate their latest research results and exchange views on the future research directions of these fields. 135 high-quality papers are included in the volume. Each paper has been peer-reviewed by at least 2 program committee members and selected by the volume editor Prof.Yanwen Wu.   On behalf of the this volume, we would like to express our sincere appreciation to all of authors and referees for their efforts reviewing the papers. Hoping you can find lots of profound research ideas and results on the related fields of Knowledge Engineering and Communication Technology. 

Elevated CO2 benefits the soil microenvironment in the rhizosphere of Robinia pseudoacacia L. seedlings in Cd- and Pb-contaminated soils.

Science.gov (United States)

Huang, Shuping; Jia, Xia; Zhao, Yonghua; Bai, Bo; Chang, Yafei

2017-02-01

Soil contamination by heavy metals in combination with elevated atmospheric CO 2 has important effects on the rhizosphere microenvironment by influencing plant growth. Here, we investigated the response of the R. pseudoacacia rhizosphere microenvironment to elevated CO 2 in combination with cadmium (Cd)- and lead (Pb)-contamination. Organic compounds (total soluble sugars, soluble phenolic acids, free amino acids, and organic acids), microbial abundance and activity, and enzyme activity (urease, dehydrogenase, invertase, and β-glucosidase) in rhizosphere soils increased significantly (p soil microbial community in the rhizosphere. Heavy metals alone resulted in an increase in total soluble sugars, free amino acids, and organic acids, a decrease in phenolic acids, microbial populations and biomass, and enzyme activity, and a change in microbial community in rhizosphere soils. Elevated CO 2 led to an increase in organic compounds, microbial populations, biomass, and activity, and enzyme activity (except for l-asparaginase), and changes in microbial community under Cd, Pb, or Cd + Pb treatments relative to ambient CO 2 . In addition, elevated CO 2 significantly (p soils. Overall, elevated CO 2 benefited the rhizosphere microenvironment of R. pseudoacacia seedlings under heavy metal stress, which suggests that increased atmospheric CO 2 concentrations could have positive effects on soil fertility and rhizosphere microenvironment under heavy metals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic Engineering

Science.gov (United States)

Phillips, John

1973-01-01

Presents a review of genetic engineering, in which the genotypes of plants and animals (including human genotypes) may be manipulated for the benefit of the human species. Discusses associated problems and solutions and provides an extensive bibliography of literature relating to genetic engineering. (JR)

Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine.

Science.gov (United States)

Vapniarsky, Natalia; Arzi, Boaz; Hu, Jerry C; Nolta, Jan A; Athanasiou, Kyriacos A

2015-10-01

The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering. Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it provides

Design and implementation of Metta, a metasearch engine for biomedical literature retrieval intended for systematic reviewers.

Science.gov (United States)

Smalheiser, Neil R; Lin, Can; Jia, Lifeng; Jiang, Yu; Cohen, Aaron M; Yu, Clement; Davis, John M; Adams, Clive E; McDonagh, Marian S; Meng, Weiyi

2014-01-01

Individuals and groups who write systematic reviews and meta-analyses in evidence-based medicine regularly carry out literature searches across multiple search engines linked to different bibliographic databases, and thus have an urgent need for a suitable metasearch engine to save time spent on repeated searches and to remove duplicate publications from initial consideration. Unlike general users who generally carry out searches to find a few highly relevant (or highly recent) articles, systematic reviewers seek to obtain a comprehensive set of articles on a given topic, satisfying specific criteria. This creates special requirements and challenges for metasearch engine design and implementation. We created a federated search tool that is connected to five databases: PubMed, EMBASE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials. Retrieved bibliographic records were shown online; optionally, results could be de-duplicated and exported in both BibTex and XML format. The query interface was extensively modified in response to feedback from users within our team. Besides a general search track and one focused on human-related articles, we also added search tracks optimized to identify case reports and systematic reviews. Although users could modify preset search options, they were rarely if ever altered in practice. Up to several thousand retrieved records could be exported within a few minutes. De-duplication of records returned from multiple databases was carried out in a prioritized fashion that favored retaining citations returned from PubMed. Systematic reviewers are used to formulating complex queries using strategies and search tags that are specific for individual databases. Metta offers a different approach that may save substantial time but which requires modification of current search strategies and better indexing of randomized controlled trial articles. We envision Metta as one piece of a multi-tool pipeline that will assist

Using Model-Based System Engineering to Provide Artifacts for NASA Project Life-Cycle and Technical Reviews Presentation

Science.gov (United States)

Parrott, Edith L.; Weiland, Karen J.

2017-01-01

This is the presentation for the AIAA Space conference in September 2017. It highlights key information from Using Model-Based Systems Engineering to Provide Artifacts for NASA Project Life-cycle and Technical Reviews paper.

Tungsten Targets the Tumor Microenvironment to Enhance Breast Cancer Metastasis

Science.gov (United States)

Bolt, Alicia M.; Sabourin, Valérie; Molina, Manuel Flores; Police, Alice M.; Negro Silva, Luis Fernando; Plourde, Dany; Lemaire, Maryse; Ursini-Siegel, Josie; Mann, Koren K.

2015-01-01

The number of individuals exposed to high levels of tungsten is increasing, yet there is limited knowledge of the potential human health risks. Recently, a cohort of breast cancer patients was left with tungsten in their breasts following testing of a tungsten-based shield during intraoperative radiotherapy. While monitoring tungsten levels in the blood and urine of these patients, we utilized the 66Cl4 cell model, in vitro and in mice to study the effects of tungsten exposure on mammary tumor growth and metastasis. We still detect tungsten in the urine of patients’ years after surgery (mean urinary tungsten concentration at least 20 months post-surgery = 1.76 ng/ml), even in those who have opted for mastectomy, indicating that tungsten does not remain in the breast. In addition, standard chelation therapy was ineffective at mobilizing tungsten. In the mouse model, tungsten slightly delayed primary tumor growth, but significantly enhanced lung metastasis. In vitro, tungsten did not enhance 66Cl4 proliferation or invasion, suggesting that tungsten was not directly acting on 66Cl4 primary tumor cells to enhance invasion. In contrast, tungsten changed the tumor microenvironment, enhancing parameters known to be important for cell invasion and metastasis including activated fibroblasts, matrix metalloproteinases, and myeloid-derived suppressor cells. We show, for the first time, that tungsten enhances metastasis in an animal model of breast cancer by targeting the microenvironment. Importantly, all these tumor microenvironmental changes are associated with a poor prognosis in humans. PMID:25324207

Tumour microenvironment and radiation response in sarcomas originating from tumourigenic human mesenchymal stem cells

DEFF Research Database (Denmark)

D'Andrea, Filippo Peder; Safwat, Akmal Ahmed; Burns, Jorge S.

2012-01-01

: Immune deficient female mice were implanted on the backs with cells from one of the clones. The subsequent tumours were subjected to either radiation treatment or had the tumour microenvironment assayed, when they reached 400mm3. Radiation was given as a single fraction of 0 to 15 Gy and the degree...

Enhanced granulocyte growth on peritoneal cell-coated membranes following irradiation: a dual effect of humoral stimulation and repair of x ray-induced damage to the microenvironment

International Nuclear Information System (INIS)

Turner, A.R.; Pfrimmer, W.J.; Boggs, D.R.; Carpe, A.I.

1978-01-01

An experimental model of the hematopoietic microenvironment was created by allowing a peritoneal cell coating to form on a disk of cellulose acetate placed in the peritoneal cavity of mice. An effective microenvironment capable of supporting colony growth, primarily granulocytic, was established if the cellulose acetate disk was in the peritoneum for 3 to 5 days. Its effectiveness was hampered by transferring it to another mouse or by exposure to toxic agents such as a propylene glycol-ethanol mixture or irradiation. An exponential dose-related decrease in colony formation was seen with increasing doses or irradiation of the microenvironment before colonization. After a low dose of irradiation, recovery of colony support capacity occurred over a 6-day period. Enhancement of colony growth was seen when cell injection was delayed for 2 to 3 days after irradiation. The effects of irradiation on the cellular stroma were separated from the systemic changes in the host by transferring an established hematopoietic microenvironment to a secondary host. It was shown that there are two distinct effects of irradiation on granulocytic colony growth; one was a short-lived period, 2 to 3 days of stimulation, presumably humoral, and the other was dose-dependent reversible microenvironment damage

Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

Science.gov (United States)

Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

2016-06-01

In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

Science.gov (United States)

Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

2016-01-01

In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, free-standing electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on-demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function. PMID:26974408

A review: Self-healing in cementitious materials and engineered cementitious composite as a self-healing material

DEFF Research Database (Denmark)

Wu, Min; Johannesson, Björn; Geiker, Mette

2012-01-01

.e. the use of hollow fibers, microencapsulation, expansive agents and mineral admixtures, bacteria and shape memory materials, are reviewed and summarized. A comparison study is conducted subsequently on different strategies to self-healing and on different healing agents used as well. Engineered...

Technical issues related to NUREG 0800, Chapter 18: Human Factors Engineering/Standard Review Plan

International Nuclear Information System (INIS)

Savage, J.W.

1982-01-01

The revision of Chapter 18 of NUREG 0800, Human Factors Engineering Standard Review Plan (SRP) will be based on SECY 82-111 and guidance contained in NUREG 0700, NUREG 0801 and NUREG 0835, plus other references. In conducting field reviews of control rooms, the NRC has identified technical issues which can be used to enhance the development of the revised version of NUREG 0800, and to establish priorities among the list of possible Branch Technical Positions (BTP) in NUREG 0800, Rev. 0, Table 18.0-2. This report is a compilation of comments and suggestions from the people who used NUREG 0700 in the Control Room field reviews. This information was used to establish possible BTP topic priorities so that the most important BTPs could be issued first. The comments and suggestions are included for HFEB review in conjunction with the table of priorities

Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach.

Science.gov (United States)

Taylor, Sophie; Spugnini, Enrico Pierluigi; Assaraf, Yehuda G; Azzarito, Tommaso; Rauch, Cyril; Fais, Stefano

2015-11-01

Despite the major progresses in biomedical research and the development of novel therapeutics and treatment strategies, cancer is still among the dominant causes of death worldwide. One of the crucial challenges in the clinical management of cancer is primary (intrinsic) and secondary (acquired) resistance to both conventional and targeted chemotherapeutics. Multiple mechanisms have been identifiedthat underlie intrinsic and acquired chemoresistance: these include impaired drug uptake, increased drug efflux, deletion of receptors, altered drug metabolism, quantitative and qualitative alterations in drug targets, increased DNA damage repair and various mechanisms of anti-apoptosis. The fast efflux of anticancer drugs mediated by multidrug efflux pumps and the partial or complete reversibility of chemoresistance combined with the absence of genetic mutations suggests a multifactorial process. However, a growing body of recent evidence suggests that chemoresistance is often triggered by the highly acidic microenvironment of tumors. The vast majority of drugs, including conventional chemotherapeutics and more recent biological agents, are weak bases that are quickly protonated and neutralized in acidic environments, such as the extracellular microenvironment and the acidic organelles of tumor cells. It is therefore essential to develop new strategies to overcome the entrapment and neutralization of weak base drugs. One such strategy is the use of proton pump inhibitors which can enhance tumor chemosensitivity by increasing the pH of the tumor microenvironment. Recent clinical trials in animals with spontaneous tumors have indicated that patient alkalization is capable of reversing acquired chemoresistance in a large percentage of tumors that are refractory to chemotherapy. Of particular interest was the benefit of alkalization for patients undergoing metronomic regimens which are becoming more widely used in veterinary medicine. Overall, these results provide

Video-rate resonant scanning multiphoton microscopy: An emerging technique for intravital imaging of the tumor microenvironment.

Science.gov (United States)

Kirkpatrick, Nathaniel D; Chung, Euiheon; Cook, Daniel C; Han, Xiaoxing; Gruionu, Gabriel; Liao, Shan; Munn, Lance L; Padera, Timothy P; Fukumura, Dai; Jain, Rakesh K

2012-01-01

The abnormal tumor microenvironment fuels tumor progression, metastasis, immune suppression, and treatment resistance. Over last several decades, developments in and applications of intravital microscopy have provided unprecedented insights into the dynamics of the tumor microenvironment. In particular, intravital multiphoton microscopy has revealed the abnormal structure and function of tumor-associated blood and lymphatic vessels, the role of aberrant tumor matrix in drug delivery, invasion and metastasis of tumor cells, the dynamics of immune cell trafficking to and within tumors, and gene expression in tumors. However, traditional multiphoton microscopy suffers from inherently slow imaging rates-only a few frames per second, thus unable to capture more rapid events such as blood flow, lymphatic flow, and cell movement within vessels. Here, we report the development and implementation of a video-rate multiphoton microscope (VR-MPLSM) based on resonant galvanometer mirror scanning that is capable of recording at 30 frames per second and acquiring intravital multispectral images. We show that the design of the system can be readily implemented and is adaptable to various experimental models. As examples, we demonstrate the utility of the system to directly measure flow within tumors, capture metastatic cancer cells moving within the brain vasculature and cells in lymphatic vessels, and image acute responses to changes in a vascular network. VR-MPLSM thus has the potential to further advance intravital imaging and provide new insight into the biology of the tumor microenvironment.

Matrix mechanics and fluid shear stress control stem cells fate in three dimensional microenvironment.

Science.gov (United States)

Chen, Guobao; Lv, Yonggang; Guo, Pan; Lin, Chongwen; Zhang, Xiaomei; Yang, Li; Xu, Zhiling

2013-07-01

Stem cells have the ability to self-renew and to differentiate into multiple mature cell types during early life and growth. Stem cells adhesion, proliferation, migration and differentiation are affected by biochemical, mechanical and physical surface properties of the surrounding matrix in which stem cells reside and stem cells can sensitively feel and respond to the microenvironment of this matrix. More and more researches have proven that three dimensional (3D) culture can reduce the gap between cell culture and physiological environment where cells always live in vivo. This review summarized recent findings on the studies of matrix mechanics that control stem cells (primarily mesenchymal stem cells (MSCs)) fate in 3D environment, including matrix stiffness and extracellular matrix (ECM) stiffness. Considering the exchange of oxygen and nutrients in 3D culture, the effect of fluid shear stress (FSS) on fate decision of stem cells was also discussed in detail. Further, the difference of MSCs response to matrix stiffness between two dimensional (2D) and 3D conditions was compared. Finally, the mechanism of mechanotransduction of stem cells activated by matrix mechanics and FSS in 3D culture was briefly pointed out.

Control of combustion generated emissions from spark ignition engines: a review

International Nuclear Information System (INIS)

Mansha, M.; Shahid, E.M.; Qureshi, A.H.

2012-01-01

For the past several decades automobiles have been a major source of ground level emissions of various pollutants like CO, HC, NO/sub x/, SO/sub x/ CO/sub 2/, etc. Due to their dangerous effects on human health, vegetation and on climate, various pre combustion, in-cylinder and post. combustion techniques have been tried for their abatement. This paper reviews all of the workable measures taken so far to controlling the combustion generated emissions from 4-stroke Spark Ignition Vehicular Engines ever since the promulgation of emission control legislation/standards and their subsequent enforcement in the late 1960s. (author)

Navy and black bean supplementation primes the colonic mucosal microenvironment to improve gut health.

Science.gov (United States)

Monk, Jennifer M; Lepp, Dion; Wu, Wenqing; Pauls, K Peter; Robinson, Lindsay E; Power, Krista A

2017-11-01

Common beans (Phaseolus vulgaris L.) are enriched in non-digestible fermentable carbohydrates and phenolic compounds that can modulate the colonic microenvironment (microbiota and host epithelial barrier) to improve gut health. In a comprehensive assessment of the impact of two commonly consumed bean varieties (differing in levels and types of phenolic compounds) within the colonic microenvironment, C57Bl/6 mice were fed diets supplemented with 20% cooked navy bean (NB) or black bean (BB) flours or an isocaloric basal diet control (BD) for 3 weeks. NB and BB similarly altered the fecal microbiota community structure (16S rRNA sequencing) notably by increasing the abundance of carbohydrate fermenting bacteria such as Prevotella, S24-7 and Ruminococcus flavefaciens, which coincided with enhanced short chain fatty acid (SCFA) production (microbial-derived carbohydrate fermentation products) and colonic expression of the SCFA receptors GPR-41/-43/-109a. Both NB and BB enhanced multiple aspects of mucus and epithelial barrier integrity vs. BD including: (i) goblet cell number, crypt mucus content and mucin mRNA expression, (ii) anti-microbial defenses (Reg3γ), (iii) crypt length and epithelial cell proliferation, (iv) apical junctional complex components (occludin, JAM-A, ZO-1 and E-cadherin) mRNA expression and (v) reduced serum endotoxin concentrations. Interestingly, biomarkers of colon barrier integrity (crypt height, mucus content, cell proliferation and goblet cell number) were enhanced in BB vs. NB-fed mice, suggesting added benefits attributable to unique BB components (e.g., phenolics). Overall, NB and BB improved baseline colonic microenvironment function by altering the microbial community structure and activity and promoting colon barrier integrity and function; effects which may prove beneficial in attenuating gut-associated diseases. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Enhanced Suppressive Activity of Regulatory T Cells in the Microenvironment of Malignant Pleural Effusions

Directory of Open Access Journals (Sweden)

Joanna Budna

2018-01-01

Full Text Available Cancer metastatic spread to serous cavity causes malignant pleural effusions (MPEs, indicating dismal prognosis. Tumor microenvironment can implement suppressive activity on host immune responses. Thus, we investigated the prevalence of Tregs and the relationship between them and TGF-β and IL-10 concentrations and measured expression of FOXP3, CTLA-4, CD28, and GITR genes, as well as protein expression of selected genes in benign effusions and MPEs. The percentage of Tregs was determined by means of multicolor flow cytometry system. TGF-β and IL-10 concentrations were measured using human TGF-β1 and IL-10 ELISA kit. Relative mRNA expression of studied genes was analyzed by real-time PCR. The frequency of Tregs was significantly higher in MPEs compared to benign effusions; however, the level of TGF-β and IL-10 in analyzed groups was comparable, and no correlation between concentrations of TGF-β and IL-10 and percentage of Tregs was observed. Relative mRNA expression of all the genes was higher in CD4+CD25+ compared to CD4+CD25− cells. In CD4+CD25+ cells from MPEs, relative mRNA expression of FOXP3, CTLA-4, and CD28 genes was significantly higher than in benign effusions; however, the level of CD4+CD25+CTLA-4+ cells in analyzed groups showed no significant differences. We found numerous genes correlations in an entire CD4+CD25+ cell subset and CD4+CD25+ cells from MPEs. Enhanced suppressive activity of Tregs is observed in the microenvironment of MPEs. Understanding of relations between cellular and cytokine immunosuppressive factors in tumor microenvironment may determine success of anticancer response.

Of plasticity and specificity: dialectics of the microenvironment and macroenvironment and the organ phenotype.

Science.gov (United States)

Bhat, Ramray; Bissell, Mina J

2014-01-01

The study of biological form and how it arises is the domain of the developmental biologists; but once the form is achieved, the organ poses a fascinating conundrum for all the life scientists: how are form and function maintained in adult organs throughout most of the life of the organism? That they do appears to contradict the inherently plastic nature of organogenesis during development. How do cells with the same genetic information arrive at, and maintain such different architectures and functions, and how do they keep remembering that they are different from each other? It is now clear that narratives based solely on genes and an irreversible regulatory dynamics cannot answer these questions satisfactorily, and the concept of microenvironmental signaling needs to be added to the equation. During development, cells rearrange and differentiate in response to diffusive morphogens, juxtacrine signals, and the extracellular matrix (ECM). These components, which constitute the modular microenvironment, are sensitive to cues from other tissues and organs of the developing embryo as well as from the external macroenvironment. On the other hand, once the organ is formed, these modular constituents integrate and constrain the organ architecture, which ensures structural and functional homeostasis and therefore, organ specificity. We argue here that a corollary of the above is that once the organ architecture is compromised in adults by mutations or by changes in the microenvironment such as aging or inflammation, that organ becomes subjected to the developmental and embryonic circuits in search of a new identity. But since the microenvironment is no longer embryonic, the confusion leads to cancer: hence as we have argued, tumors become new evolutionary organs perhaps in search of an elusive homeostasis. © 2013 Wiley Periodicals, Inc.

Cellular Microenvironment Dictates Androgen Production by Murine Fetal Leydig Cells in Primary Culture1

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Carney, Colleen M.; Muszynski, Jessica L.; Strotman, Lindsay N.; Lewis, Samantha R.; O'Connell, Rachel L.; Beebe, David J.; Theberge, Ashleigh B.; Jorgensen, Joan S.

2014-01-01

ABSTRACT Despite the fact that fetal Leydig cells are recognized as the primary source of androgens in male embryos, the mechanisms by which steroidogenesis occurs within the developing testis remain unclear. A genetic approach was used to visualize and isolate fetal Leydig cells from remaining cells within developing mouse testes. Cyp11a1-Cre mice were bred to mT/mG dual reporter mice to target membrane-tagged enhanced green fluorescent protein (GFP) within steroidogenic cells, whereas other cells expressed membrane-tagged tandem-dimer tomato red. Fetal Leydig cell identity was validated using double-labeled immunohistochemistry against GFP and the steroidogenic enzyme 3beta-HSD, and cells were successfully isolated as indicated by qPCR results from sorted cell populations. Because fetal Leydig cells must collaborate with neighboring cells to synthesize testosterone, we hypothesized that the fetal Leydig cell microenvironment defined their capacity for androgen production. Microfluidic culture devices were used to measure androstenedione and testosterone production of fetal Leydig cells that were cultured in cell-cell contact within a mixed population, were isolated but remained in medium contact via compartmentalized co-culture with other testicular cells, or were isolated and cultured alone. Results showed that fetal Leydig cells maintained their identity and steroidogenic activity for 3–5 days in primary culture. Microenvironment dictated proficiency of testosterone production. As expected, fetal Leydig cells produced androstenedione but not testosterone when cultured in isolation. More testosterone accumulated in medium from mixed cultures than from compartmentalized co-cultures initially; however, co-cultures maintained testosterone synthesis for a longer time. These data suggest that a combination of cell-cell contact and soluble factors constitute the ideal microenvironment for fetal Leydig cell activity in primary culture. PMID:25143354

Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland

Science.gov (United States)

2017-11-01

Danvers, MA, USA), andro- gen receptor (1:500, Santa Cruz Biotechnologies, Santa Cruz, CA, USA) and guinea pig antibodies against Vimentin (1:1,000...Problems…………………………………………………….29 6. Products ………………………………………………………………..29-30 7. Participants/Collaborators……………………………………………30-31 8. Special Reporting...a prometastatic microenvironment. The production of the Ltbp1-TGF-beta complex by luminal cells has consequences for our understanding of the

Interleukin 33 in tumor microenvironment is crucial for the accumulation and function of myeloid-derived suppressor cells

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Xiao, Peng; Wan, Xiaopeng; Cui, Bijun; Liu, Yang; Qiu, Chenyang; Rong, Jiabing; Zheng, Mingzhu; Song, Yinjing; Chen, Luoquan; He, Jia; Tan, Qinchun; Wang, Xiaojia; Shao, Xiying; Liu, Yuhua; Cao, Xuetao; Wang, Qingqing

2016-01-01

ABSTRACT Tumor-induced, myeloid-derived suppressor cells (MDSCs)-mediated immune dysfunction is an important mechanism that leads to tumor immune escape and the inefficacy of cancer immunotherapy. Importantly, tumor-infiltrating MDSCs have much stronger ability compared to MDSCs in the periphery. However, the mechanisms that tumor microenvironment induces the accumulation and function of MDSCs are poorly understood. Here, we report that Interleukin-33 (IL-33) – a cytokine which can be abundantly released in tumor tissues both in 4T1-bearing mice and breast cancer patients, is crucial for facilitating the expansion of MDSCs. IL-33 in tumor microenvironment reduces the apoptosis and sustains the survival of MDSCs through induction of autocrine secretion of GM-CSF, which forms a positive amplifying loop for MDSC accumulation. This is in conjunction with IL-33-driven induction of arginase-1 expression and activation of NF-κB and MAPK signaling in MDSCs which augments their immunosuppressive ability, and histone modifications were involved in IL-33 signaling in MDSCs. In ST2−/− mice, the defect of IL-33 signaling in MDSCs attenuates the immunosuppressive and pro-tumoral capacity of MDSCs. Our results identify IL-33 as a critical mediator that contributes to the abnormal expansion and enhanced immunosuppressive function of MDSCs within tumor microenvironment, which can be potentially targeted to reverse MDSC-mediated tumor immune evasion. PMID:26942079

Inhibition of Siah2 Ubiquitin Ligase by Vitamin K3 Attenuates Chronic Myeloid Leukemia Chemo-Resistance in Hypoxic Microenvironment.

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Huang, Jixian; Lu, Ziyuan; Xiao, Yajuan; He, Bolin; Pan, Chengyun; Zhou, Xuan; Xu, Na; Liu, Xiaoli

2018-02-05

BACKGROUND A hypoxic microenvironment is associated with resistance to tyrosine kinase inhibitors (TKIs) and a poor prognosis in chronic myeloid leukemia (CML). The E3 ubiquitin ligase Siah2 plays a vital role in the regulation of hypoxia response, as well as in leukemogenesis. However, the role of Siah2 in CML resistance is unclear, and it is unknown whether vitaminK3 (a Siah2 inhibitor) can improve the chemo-sensitivity of CML cells in a hypoxic microenvironment. MATERIAL AND METHODS The expression of Siah2 was detected in CML patients (CML-CP and CML-BC), K562 cells, and K562-imatinib-resistant cells (K562-R cells). We measured the expression of PHD3, HIF-1α, and VEGF in both cell lines under normoxia and hypoxic conditions, and the degree of leukemic sensitivity to imatinib and VitaminK3 were evaluated. RESULTS Siah2 was overexpressed in CML-BC patients (n=9) as compared to CML-CP patients (n=13). Similarly, K562-imatinib-resistant cells (K562-R cells) showed a significantly higher expression of Siah2 as compared to K562 cells in a hypoxic microenvironment. Compared to normoxia, under hypoxic conditions, both cell lines had lower PHD3, higher HIF-1α, and higher VEGF expression. Additionally, Vitamin K3 (an inhibitor of Siah2) reversed these changes and promoted a higher degree of leukemic sensitivity to imatinib. CONCLUSIONS Our findings indicate that the Siah2-PHD3- HIF-1α-VEGF axis is an important hypoxic signaling pathway in a leukemic microenvironment. An inhibitor of Siah2, combined with TKIs, might be a promising therapy for relapsing and refractory CML patients.

Clay-based materials for engineered barriers: a review

International Nuclear Information System (INIS)

Lajudie, A.; Raynal, J.; Petit, J.C.; Toulhoat, P.

1994-01-01

The potential importance of backfilling and plugging in underground radioactive waste repositories has led different research institutions to carry out extensive studies of swelling clay materials for the development of engineered barriers in underground conditions. These materials should combine a variety of hydro-thermo-mechanical and geochemical properties: impermeability, swelling ability in order to fill all void space, heat transfer and retention capacity for the most noxious radionuclides. Smectite clays best exhibit these properties and most of the research effort has been devoted to this type of materials. In this paper, mineralogical composition, sodium or calcium content, thermo-hydro-mechanical properties, swelling pressure, hydraulic and thermal conductivity, and chemical properties of five smectite clays selected by five major nuclear countries are reviewed: Avonseal montmorillonite (Canada), MX 80 montmorillonite (Sweden), Montigel montmorillonite (Switzerland), S-2 montmorillonite (Spain), and Fo-Ca inter stratified kaolinite/beidellite (France). (J.S.). 29 refs., 5 figs., 3 tabs

Genetically engineered mesenchymal stromal cells produce IL-3 and TPO to further improve human scaffold-based xenograft models.

Science.gov (United States)

Carretta, Marco; de Boer, Bauke; Jaques, Jenny; Antonelli, Antonella; Horton, Sarah J; Yuan, Huipin; de Bruijn, Joost D; Groen, Richard W J; Vellenga, Edo; Schuringa, Jan Jacob

2017-07-01

Recently, NOD-SCID IL2Rγ -/- (NSG) mice were implanted with human mesenchymal stromal cells (MSCs) in the presence of ceramic scaffolds or Matrigel to mimic the human bone marrow (BM) microenvironment. This approach allowed the engraftment of leukemic samples that failed to engraft in NSG mice without humanized niches and resulted in a better preservation of leukemic stem cell self-renewal properties. To further improve our humanized niche scaffold model, we genetically engineered human MSCs to secrete human interleukin-3 (IL-3) and thrombopoietin (TPO). In vitro, these IL-3- and TPO-producing MSCs were superior in expanding human cord blood (CB) CD34 + hematopoietic stem/progenitor cells. MLL-AF9-transduced CB CD34 + cells could be transformed efficiently along myeloid or lymphoid lineages on IL-3- and TPO-producing MSCs. In vivo, these genetically engineered MSCs maintained their ability to differentiate into bone, adipocytes, and other stromal components. Upon transplantation of MLL-AF9-transduced CB CD34 + cells, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) developed in engineered scaffolds, in which a significantly higher percentage of myeloid clones was observed in the mouse compartments compared with previous models. Engraftment of primary AML, B-cell ALL, and biphenotypic acute leukemia (BAL) patient samples was also evaluated, and all patient samples could engraft efficiently; the myeloid compartment of the BAL samples was better preserved in the human cytokine scaffold model. In conclusion, we show that we can genetically engineer the ectopic human BM microenvironment in a humanized scaffold xenograft model. This approach will be useful for functional study of the importance of niche factors in normal and malignant human hematopoiesis. Copyright © 2017 ISEH - International Society for Experimental Hematology. All rights reserved.

Tissue Engineering-based Therapeutic Strategies for Vocal Fold Repair and Regeneration

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Li, Linqing; Stiadle, Jeanna M.; Lau, Hang K.; Zerdoum, Aidan B.; Jia, Xinqiao; L.Thibeault, Susan; Kiick, Kristi L.

2016-01-01

Vocal folds are soft laryngeal connective tissues with distinct layered structures and complex multicomponent matrix compositions that endow phonatory and respiratory functions. This delicate tissue is easily damaged by various environmental factors and pathological conditions, altering vocal biomechanics and causing debilitating vocal disorders that detrimentally affect the daily lives of suffering individuals. Modern techniques and advanced knowledge of regenerative medicine have led to a deeper understanding of the microstructure, microphysiology, and micropathophysiology of vocal fold tissues. State-of-the-art materials ranging from extracecullar-matrix (ECM)-derived biomaterials to synthetic polymer scaffolds have been proposed for the prevention and treatment of voice disorders including vocal fold scarring and fibrosis. This review intends to provide a thorough overview of current achievements in the field of vocal fold tissue engineering, including the fabrication of injectable biomaterials to mimic in vitro cell microenvironments, novel designs of bioreactors that capture in vivo tissue biomechanics, and establishment of various animal models to characterize the in vivo biocompatibility of these materials. The combination of polymeric scaffolds, cell transplantation, biomechanical stimulation, and delivery of antifibrotic growth factors will lead to successful restoration of functional vocal folds and improved vocal recovery in animal models, facilitating the application of these materials and related methodologies in clinical practice. PMID:27619243

Inorganic Arsenic–Related Changes in the Stromal Tumor Microenvironment in a Prostate Cancer Cell–Conditioned Media Model

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Shearer, Joseph J.; Wold, Eric A.; Umbaugh, Charles S.; Lichti, Cheryl F.; Nilsson, Carol L.; Figueiredo, Marxa L.

2015-01-01

Background: The tumor microenvironment plays an important role in the progression of cancer by mediating stromal–epithelial paracrine signaling, which can aberrantly modulate cellular proliferation and tumorigenesis. Exposure to environmental toxicants, such as inorganic arsenic (iAs), has also been implicated in the progression of prostate cancer. Objective: The role of iAs exposure in stromal signaling in the tumor microenvironment has been largely unexplored. Our objective was to elucidate molecular mechanisms of iAs-induced changes to stromal signaling by an enriched prostate tumor microenvironment cell population, adipose-derived mesenchymal stem/stromal cells (ASCs). Results: ASC-conditioned media (CM) collected after 1 week of iAs exposure increased prostate cancer cell viability, whereas CM from ASCs that received no iAs exposure decreased cell viability. Cytokine array analysis suggested changes to cytokine signaling associated with iAs exposure. Subsequent proteomic analysis suggested a concentration-dependent alteration to the HMOX1/THBS1/TGFβ signaling pathway by iAs. These results were validated by quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blotting, confirming a concentration-dependent increase in HMOX1 and a decrease in THBS1 expression in ASC following iAs exposure. Subsequently, we used a TGFβ pathway reporter construct to confirm a decrease in stromal TGFβ signaling in ASC following iAs exposure. Conclusions: Our results suggest a concentration-dependent alteration of stromal signaling: specifically, attenuation of stromal-mediated TGFβ signaling following exposure to iAs. Our results indicate iAs may enhance prostate cancer cell viability through a previously unreported stromal-based mechanism. These findings indicate that the stroma may mediate the effects of iAs in tumor progression, which may have future therapeutic implications. Citation: Shearer JJ, Wold EA, Umbaugh CS, Lichti CF, Nilsson CL

Phenotypic characterization of prostate cancer LNCaP cells cultured within a bioengineered microenvironment.

Directory of Open Access Journals (Sweden)

Shirly Sieh

Full Text Available Biophysical and biochemical properties of the microenvironment regulate cellular responses such as growth, differentiation, morphogenesis and migration in normal and cancer cells. Since two-dimensional (2D cultures lack the essential characteristics of the native cellular microenvironment, three-dimensional (3D cultures have been developed to better mimic the natural extracellular matrix. To date, 3D culture systems have relied mostly on collagen and Matrigel™ hydrogels, allowing only limited control over matrix stiffness, proteolytic degradability, and ligand density. In contrast, bioengineered hydrogels allow us to independently tune and systematically investigate the influence of these parameters on cell growth and differentiation. In this study, polyethylene glycol (PEG hydrogels, functionalized with the Arginine-glycine-aspartic acid (RGD motifs, common cell-binding motifs in extracellular matrix proteins, and matrix metalloproteinase (MMP cleavage sites, were characterized regarding their stiffness, diffusive properties, and ability to support growth of androgen-dependent LNCaP prostate cancer cells. We found that the mechanical properties modulated the growth kinetics of LNCaP cells in the PEG hydrogel. At culture periods of 28 days, LNCaP cells underwent morphogenic changes, forming tumor-like structures in 3D culture, with hypoxic and apoptotic cores. We further compared protein and gene expression levels between 3D and 2D cultures upon stimulation with the synthetic androgen R1881. Interestingly, the kinetics of R1881 stimulated androgen receptor (AR nuclear translocation differed between 2D and 3D cultures when observed by immunofluorescent staining. Furthermore, microarray studies revealed that changes in expression levels of androgen responsive genes upon R1881 treatment differed greatly between 2D and 3D cultures. Taken together, culturing LNCaP cells in the tunable PEG hydrogels reveals differences in the cellular responses to

Human Breast Cancer Cells Are Redirected to Mammary Epithelial Cells upon Interaction with the Regenerating Mammary Gland Microenvironment In-Vivo

Science.gov (United States)

Bussard, Karen M.; Smith, Gilbert H.

2012-01-01

Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display ‘normal’ behavior when placed into ‘normal’ ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for ‘normal’ gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts) confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini) were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic) respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo. PMID:23155468

Human breast cancer cells are redirected to mammary epithelial cells upon interaction with the regenerating mammary gland microenvironment in-vivo.

Directory of Open Access Journals (Sweden)

Karen M Bussard

Full Text Available Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display 'normal' behavior when placed into 'normal' ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for 'normal' gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo.

Choline-Deficient-Diet-Induced Fatty Liver Is a Metastasis-Resistant Microenvironment.

Science.gov (United States)

Nakamura, Miki; Suetsugu, Atsushi; Hasegawa, Kosuke; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Hoffman, Robert M

2017-07-01

Fatty liver disease is increasing in the developed and developing world. Liver metastasis from malignant lymphoma in the fatty liver is poorly understood. In a previous report, we developed color-coded imaging of the tumor microenvironment (TME) of the murine EL4-RFP malignant lymphoma during metastasis, including the lung. In the present report, we investigated the potential and microenvironment of the fatty liver induced by a choline-deficient diet as a metastatic site in this mouse lymphoma model. C57BL/6-GFP transgenic mice were fed with a choline-deficient diet in order to establish a fatty liver model. EL4-RFP cells were injected in the spleen of normal mice and fatty-liver mice. Metastases in mice with fatty liver or normal liver were imaged with the Olympus SZX7 microscope and the Olympus FV1000 confocal microscope. Metastases of EL4-RFP were observed in the liver, ascites and bone marrow. Primary tumors were imaged in the spleen at the injection site. The fewest metastases were observed in the fatty liver. In addition, the fewest cancer-associated fibroblasts (CAFs) were observed in the fatty liver. The relative metastatic resistance of the fatty liver may be due to the reduced number of CAFs in the fatty livers. The mechanism of the effect of the choline-deficient diet is discussed. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Engine Tune-up Service. Unit 6: Emission Control Systems. Review Exercise Book. Automotive Mechanics Curriculum.

Science.gov (United States)

Bacon, E. Miles

This book of pretests and review exercises is designed to accompany the Engine Tune-Up Service Student Guide for Unit 6, Emission Control Systems, available separately as CE 031 220. Focus of the exercises and pretests is inspecting, testing, and servicing emission control systems. Pretests and performance checklists are provided for each of the…

Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.

Science.gov (United States)

Gaut, Carrie; Sugaya, Kiminobu

2015-01-01

Articular cartilage defects often progress to osteoarthritis, which negatively impacts quality of life for millions of people worldwide and leads to high healthcare expenditures. Tissue engineering approaches to osteoarthritis have concentrated on proliferation and differentiation of stem cells by activation and suppression of signaling pathways, and by using a variety of scaffolding techniques. Recent studies indicate a key role of environmental factors in the differentiation of mesenchymal stem cells to mature cartilage-producing chondrocytes. Therapeutic approaches that consider environmental regulation could optimize chondrogenesis protocols for regeneration of articular cartilage. This review focuses on the effect of scaffold structure and composition, mechanical stress and hypoxia in modulating mesenchymal stem cell fate and the current use of these environmental factors in tissue engineering research.

Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function.

Science.gov (United States)

Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

2016-06-01

In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

A systematic review of applying modern software engineering techniques to developing robotic systems

Directory of Open Access Journals (Sweden)

Claudia Pons

2012-01-01

Full Text Available Robots have become collaborators in our daily life. While robotic systems become more and more complex, the need to engineer their software development grows as well. The traditional approaches used in developing these software systems are reaching their limits; currently used methodologies and tools fall short of addressing the needs of such complex software development. Separating robotics’ knowledge from short-cycled implementation technologies is essential to foster reuse and maintenance. This paper presents a systematic review (SLR of the current use of modern software engineering techniques for developing robotic software systems and their actual automation level. The survey was aimed at summarizing existing evidence concerning applying such technologies to the field of robotic systems to identify any gaps in current research to suggest areas for further investigation and provide a background for positioning new research activities.

New and paradoxical roles of matrix metalloproteinases in the tumor microenvironment

DEFF Research Database (Denmark)

Noël, Agnès; Gutiérrez-Fernández, Ana; Sounni, Nor Eddine

2012-01-01

Processes such as cell proliferation, angiogenesis, apoptosis, or invasion are strongly influenced by the surrounding microenvironment of the tumor. Therefore, the ability to change these surroundings represents an important property through which tumor cells are able to acquire specific functions....... Despite the pro-tumorigenic function of certain metalloproteinases, recent studies have shown that other members of these families, such as MMP8 or MMP11, have a protective role against tumor growth and metastasis in animal models. These studies have been further expanded by large-scale genomic analysis...

A study on the effects of relativistic heavy charged particles on the cellular microenvironment

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Costes, Sylvain Vincent

This study was done under the National Aeronautics Space Administration (NASA) effort to assess the effect of cosmic radiation on astronauts during a 3 year mission to Mars. Carcinogenesis is known to be induced more efficiently by cosmic radiation. Our attention was turned towards one of the most efficient cosmic particles in inducing cancer, relativistic Fe, and focused in assessing its effect on the cellular microenvironment (ECM). Previous observations on mammary glands were showing irregularities in the immunoreactivity of the ECM protein laminin one hour after whole body irradiation with 1GeV/amu Fe ions for a dose of 0.8 Gy. This effect was not observed after 5 Gy γ-rays exposure. The rapidity of such a change suggested that the effect might be due to a physical event specific to relativistic charged particles (HZE), rather than a biological event. Our study showed that this effect is actually a complex and rapid response of the microenvironment to highly ionizing radiation. It involves a fast disruption of the basement membrane of the ECM induced by the highly localized ionization and reactive oxygen formation around the track of the Fe ion. This disruption triggers further chemical and biological responses involved in the remodeling of the laminin network in the basement membrane. A metalloproteinase is suspected to be the intermediate protease affecting laminin. The HZE effect on the microenvironment was seen in both mouse mammary glands and skin, but the laminin isoforms sensitive to Fe ions were different for each organ, with a clear disruption of laminin-1 network in skin and of laminin-5 in mammary glands. In addition, the laminin receptor integrins seem to be involved in this mechanism, but its contribution is unclear at this point. Finally, such studies suggest a shift from the concept of relative biological effectiveness (RBE) used in classical radiation biology since the effect is only seen with HZE at viable whole body doses. In addition, this

A Review of Multi-Sensory Technologies in a Science, Technology, Engineering, Arts and Mathematics (STEAM) Classroom

Science.gov (United States)

Taljaard, Johann

2016-01-01

This article reviews the literature on multi-sensory technology and, in particular, looks at answering the question: "What multi-sensory technologies are available to use in a science, technology, engineering, arts and mathematics (STEAM) classroom, and do they affect student engagement and learning outcomes?" Here engagement is defined…

The role of laminins in cartilaginous tissues: from development to regeneration

Directory of Open Access Journals (Sweden)

Y Sun

2017-07-01

Full Text Available As a key molecule of the extracellular matrix, laminin provides a delicate microenvironment for cell functions. Recent findings suggest that laminins expressed by cartilage-forming cells (chondrocytes, progenitor cells and stem cells could promote chondrogenesis. However, few papers outline the effect of laminins on providing a favorable matrix microenvironment for cartilage regeneration. In this review, we delineated the expression of laminins in hyaline cartilage, fibrocartilage and cartilage-like tissue (nucleus pulposus throughout several developmental stages. We also examined the effect of laminins on the biological activities of chondrocytes, including adhesion, migration and survival. Furthermore, we scrutinized the potential influence of various laminin isoforms on cartilage-forming cells’ proliferation and chondrogenic differentiation. With this information, we hope to facilitate the understanding of the spatial and temporal interactions between cartilage-forming cells and laminin microenvironment to eventually advance cell-based cartilage engineering and regeneration.

Using smartphone as a motion detector to collect time-microenvironment data for estimating the inhalation dose

International Nuclear Information System (INIS)

Hoi, Tran Xuan; Phuong, Huynh Truc; Van Hung, Nguyen

2016-01-01

During the production of iodine-131 from neutron irradiated tellurium dioxide by the dry distillation, a considerable amount of "1"3"1I vapor is dispersed to the indoor air. People who routinely work at the production area may result in a significant risk of exposure to chronic intake by inhaled "1"3"1I. This study aims to estimate the inhalation dose for individuals manipulating the "1"3"1I at a radioisotope production. By using an application installed on smartphones, we collected the time-microenvironment data spent by a radiation group during work days in 2015. Simultaneously, we used a portable air sampler combined with radioiodine cartridges for grabbing the indoor air samples and then the daily averaged "1"3"1I concentration was calculated. Finally, the time-microenvironment data jointed with the concentration to estimate the inhalation dose for the workers. The result showed that most of the workers had the annual internal dose in 1÷6 mSv. We concluded that using smartphone as a motion detector is a possible and reliable way instead of the questionnaires, diary or GPS-based method. It is, however, only suitable for monitoring on fixed indoor environments and limited the targeted people. - Highlights: • We constructed the time-microenvironment patterns with 1-min resolution by using a smartphone application. • Exposure to "1"3"1I at the dry distillation areas may lead to an acute inhalation dose significantly. • Using smartphone as a motion detector in indoor exposure monitoring is a reliable method.

Indoor-outdoor concentrations of fine particulate matter in school building microenvironments near a mine tailing deposit

Directory of Open Access Journals (Sweden)

Leonardo Martínez

2016-11-01

Full Text Available Indoor air quality in school classrooms is a major pediatric health concern because children are highly susceptible to adverse effects from xenobiotic exposure. Fine particulate matter (PM2.5 emitted from mining waste deposits within and near cities in northern Chile is a serious environmental problem. We measured PM2.5 in school microenvironments in urban areas of Chañaral, a coastal community whose bay is contaminated with mine tailings. PM2.5 levels were measured in six indoor and outdoor school environments during the summer and winter of 2012 and 2013. Measurements were taken during school hours on two consecutive days. Indoor PM2.5 concentrations were 12.53–72.38 μg/m3 in the summer and 21.85–100.53 μg/m3 in winter, while outdoor concentrations were 11.86–181.73 μg/m3 in the summer and 21.50–93.07 μg/m3 in winter. Indoor/outdoor ratios were 0.17–2.76 in the summer and 0.64–4.49 in winter. PM2.5 levels were higher in indoor microenvironments during the winter, at times exceeding national and international recommendations. Our results demonstrate that indoor air quality Chañaral school microenvironments is closely associated with outdoor air pollution attributable to the nearby mine tailings. Policymakers should enact environmental management strategies to minimize further environmental damage and mitigate the risks that this pollution poses for pediatric health.

Human cancer risk estimation for 1,3-butadiene: An assessment of personal exposure and different microenvironments.

Science.gov (United States)

Huy, Lai Nguyen; Lee, Shun Cheng; Zhang, Zhuozhi

2018-03-01

This study estimated the lifetime cancer risk (LCR) attributable to 1,3-butadiene (BD) personal exposure and to other microenvironments, including residential home, outdoor, in-office, in-vehicle, and dining. Detailed life expectancy by country (WHO), inhalation rate and body weight by gender reported by USEPA were used for the calculation, focusing on adult population (25≤Agepersonal exposure exceeded the USEPA benchmark of 1×10 -6 in many cities. For outdoor BD exposure, LCR estimations in 45 out of 175 cities/sites (sharing 26%) exceeded the USEPA benchmark. Out of the top 20 cities having high LCR estimations, developing countries contributed 19 cities, including 14, 3, 1, 1 cities in China, India, Chile, and Pakistan. One city in the United States was in the list due to the nearby industrial facilities. The LCR calculations for BD levels found in residential home, in-vehicle and dining microenvironments also exceeded 1×10 -6 in some cities, while LCR caused by in-office BD levels had the smallest risk. Four cities/regions were used for investigating source distributions to total LCR results because of their sufficient BD data. Home exposure contributed significantly to total LCR value (ranging 56% to 86%), followed by in-vehicle (4% to 38%) and dining (4 to 7%). Outdoor microenvironment shared highly in Tianjin with 6%, whereas in-office contributed from 2-3% for all cities. High LCR estimations found in developing countries highlighted the greater cancer risk caused by BD in other cities without available measurement data. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting Angiogenesis and Tumor Microenvironment in Metastatic Colorectal Cancer: Role of Aflibercept

Directory of Open Access Journals (Sweden)

Guido Giordano

2014-01-01

Full Text Available In the last decades, we have progressively observed an improvement in therapeutic options for metastatic colorectal cancer (mCRC treatment with a progressive prolongation of survival. mCRC prognosis still remains poor with low percentage of 5-year survival. Targeted agents have improved results obtained with standard chemotherapy. Angiogenesis plays a crucial role in colorectal cancer growth, proliferation, and metastasization and it has been investigated as a potential target for mCRC treatment. Accordingly, novel antiangiogenic targeted agents bevacizumab, regorafenib, and aflibercept have been approved for mCRC treatment as the result of several phase III randomized trials. The development of a tumor permissive microenvironment via the aberrant expression by tumor cells of paracrine factors alters the tumor-stroma interactions inducing an expansion of proangiogenic signals. Recently, the VELOUR study showed that addition of aflibercept to FOLFIRI regimen as a second-line therapy for mCRC improved significantly OS, PFS, and RR. This molecule represents a valid second-line therapeutic option and its peculiar ability to interfere with placental growth factor (PlGF/vascular endothelial growth factor receptor 1 (VEGFR1 axis makes it effective in targeting angiogenesis, inflammatory cells and in overcoming resistances to anti-angiogenic first-line treatment. Here, we discuss about Aflibercept peculiar ability to interfere with tumor microenvironment and angiogenic pathway.

Hidden in plain view: feminists doing engineering ethics, engineers doing feminist ethics.

Science.gov (United States)

Riley, Donna

2013-03-01

How has engineering ethics addressed gender concerns to date? How have the ideas of feminist philosophers and feminist ethicists made their way into engineering ethics? What might an explicitly feminist engineering ethics look like? This paper reviews some major themes in feminist ethics and then considers three areas in which these themes have been taken up in engineering ethics to date. First, Caroline Whitbeck's work in engineering ethics integrates considerations from her own earlier writings and those of other feminist philosophers, but does not use the feminist label. Second, efforts to incorporate the Ethic of Care and principles of Social Justice into engineering have drawn on feminist scholarship and principles, but these commitments can be lost in translation to the broader engineering community. Third, the film Henry's Daughters brings gender considerations into the mainstream of engineering ethics, but does not draw on feminist ethics per se; despite the best intentions in broaching a difficult subject, the film unfortunately does more harm than good when it comes to sexual harassment education. I seek not only to make the case that engineers should pay attention to feminist ethics and engineering ethicists make more use of feminist ethics traditions in the field, but also to provide some avenues for how to approach integrating feminist ethics in engineering. The literature review and analysis of the three examples point to future work for further developing what might be called feminist engineering ethics.

Reviews of the In-situ Demonstration Test of the Engineered Barrier System in Many Countries

Energy Technology Data Exchange (ETDEWEB)

Lee, Minsoo; Choi, Heui Joo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-10-15

Many nations considering the deep geologic disposal of HLW are now planning or executing in-situ demonstration experiments on their regional EBS (Engineering barrier system) at their deep underground research facilities. The main purpose of the in-situ EBS test is the experimental confirmation of its performance, and the prediction of its long-term evolution through the modeling of EBS based on the experimental data. Additionally, the engineering feasibility for the construction of an engineering barrier system can also be checked through full scale construction of an in-situ test. KAERI is currently preparing an in-situ test at a large 1/3 scale, called IN-DEBS (In-situ Demonstration of EBS) at KURT (KAERI Underground Research Tunnel) for the generic EBS suggested in A-KRS (Advanced KAERI Reference System), which was developed to treat the HLW from pyroprocessing. As the first step for the design of IN-DEBS, the foreign in-situ demonstrations of EBS were reviewed in this paper. The demonstration projects, which were completed or are still being executed in some countries such as Sweden, France, Finland, Canada, Belgium, Switzerland, Spain, and Japan, were surveyed and summarized. In particular, hardware constitutions such as the heating element or compact bentonite, and the experimental procedures, have focused more on reviews than on experimental results in this survey, since their hardware information is very important for the design of the IN-DEBS.

Reviews of the In-situ Demonstration Test of the Engineered Barrier System in Many Countries

International Nuclear Information System (INIS)

Lee, Minsoo; Choi, Heui Joo

2013-01-01

Many nations considering the deep geologic disposal of HLW are now planning or executing in-situ demonstration experiments on their regional EBS (Engineering barrier system) at their deep underground research facilities. The main purpose of the in-situ EBS test is the experimental confirmation of its performance, and the prediction of its long-term evolution through the modeling of EBS based on the experimental data. Additionally, the engineering feasibility for the construction of an engineering barrier system can also be checked through full scale construction of an in-situ test. KAERI is currently preparing an in-situ test at a large 1/3 scale, called IN-DEBS (In-situ Demonstration of EBS) at KURT (KAERI Underground Research Tunnel) for the generic EBS suggested in A-KRS (Advanced KAERI Reference System), which was developed to treat the HLW from pyroprocessing. As the first step for the design of IN-DEBS, the foreign in-situ demonstrations of EBS were reviewed in this paper. The demonstration projects, which were completed or are still being executed in some countries such as Sweden, France, Finland, Canada, Belgium, Switzerland, Spain, and Japan, were surveyed and summarized. In particular, hardware constitutions such as the heating element or compact bentonite, and the experimental procedures, have focused more on reviews than on experimental results in this survey, since their hardware information is very important for the design of the IN-DEBS

Science review of internal combustion engines

International Nuclear Information System (INIS)

Taylor, Alex M.K.P.

2008-01-01

Internal combustion engines used in transportation produce about 23% of the UK's carbon dioxide emission, up from 14% in 1980. The current science described in this paper suggests that there could be 6-15% improvements in internal combustion fuel efficiency in the coming decade, although filters to meet emission legislation reduce these gains. Using these engines as hybrids with electric motors produces a reduction in energy requirements in the order of 21-28%. Developments beyond the next decade are likely to be dominated by four topics: emission legislation and emission control, new fuels, improved combustion and a range of advanced concepts for energy saving. Emission control is important because current methods for limiting nitrogen oxides and particulate emissions imply extra energy consumption. Of the new fuels, non-conventional fossil-derived fuels are associated with larger greenhouse gas emissions than conventional petroleum-based fuels, while a vehicle propelled by fuel cells consuming non-renewable hydrogen does not necessarily offer an improvement in emissions over the best hybrid internal combustion engines. Improved combustion may be developed for both gasoline and diesel fuels and promises better efficiency as well as lower noxious emissions without the need for filtering. Finally, four advanced concepts are considered: new thermodynamic cycles, a Rankine bottoming cycle, electric turbo-compounding and the use of thermoelectric devices. The latter three all have the common theme of trying to extract energy from waste heat, which represents about 30% of the energy input to an internal combustion engine

Extracellular matrix inspired surface functionalization with heparin, fibronectin and VEGF provides an anticoagulant and endothelialization supporting microenvironment

International Nuclear Information System (INIS)

Wang, Xue; Liu, Tao; Chen, Yuan; Zhang, Kun; Maitz, Manfred F.; Pan, Changjiang; Chen, Junying; Huang, Nan

2014-01-01

Highlights: • Surface modification with fibronectin, heparin and VEGF could selectively anticoagulant and promote endothelialization. • The bioactivity of biomolecules was more efficiently maintained via specific intermolecular interaction. • Poly-l-lysine interlayer was more feasible and the degradation product had no harm to human body. - Abstract: The biocompatibility of currently used coronary artery stent is still far from perfect, which closely related to insufficient endothelialization and thrombus formation. In this study, heparin, fibronectin and VEGF were immobilized on Ti surface to construct a multifunctional microenvironment with favorable properties to inhibit thrombosis formation and promote endothelialization simultaneously. The microenvironment on Ti surface was characterized in detail and demonstrated that the Hep/Fn/VEGF biofunctional coating was constructed successfully on Ti surface. The influence of surface properties such as chemical composition, roughness, hydrophilicity, and binding density of biomolecules on the performances of hemocompatibility and cytocompatibility was evaluated and discussed. Modified surface significantly enhanced the AT III binding density and prolonged the clotting time. In vitro platelet adhesion and activation assays further proved that the modified surface presented favorable anti-coagulant property. In addition, the proliferation of endothelial progenitor cells (EPCs) and endothelial cells (ECs) on the Hep/Fn/VEGF biofunctional coating was significantly promoted. In conclusion, the Hep/Fn/VEGF biofunctional coating was successfully constructed with desirable anticoagulant and endothelialization supporting properties. This work may provide a promising approach for biofunctional surface modification of coronary artery stent to acquire a desired multifunctional microenvironment

Human mammary progenitor cell fate decisions are productsof interactions with combinatorial microenvironments

DEFF Research Database (Denmark)

LaBarge, Mark A.; Nelson, Celeste M.; Villadsen, René

2009-01-01

factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify...... combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells.Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well...

Molecular characterization and geological microenvironment of a microbial community inhabiting weathered receding shale cliffs.

Science.gov (United States)

Cockell, Charles S; Pybus, David; Olsson-Francis, Karen; Kelly, Laura; Petley, David; Rosser, Nick; Howard, Kieren; Mosselmans, Fred

2011-01-01

Shales play an important role in many earth system processes including coastal erosion, and they form the foundations of many engineering structures. The geobiology of the interior of pyrite-containing receding shale cliffs on the coast of northeast England was examined. The surface of the weathered shales was characterised by a thin layer of disordered authigenic iron oxyhydroxides and localised acicular, platy and aggregated gypsum, which was characterised by Raman spectroscopy, XAS and SEM. These chemical changes are likely to play an important role in causing rock weakening along fractures at the micron scale, which ultimately lead to coastal retreat at the larger scale. The surface of the shale hosts a novel, low-diversity microbial community. The bacterial community was dominated by Proteobacteria, with phylotypes closely associating with Methylocella and other members of the γ-subdivision. The second largest phylogenetic group corresponded to Nitrospira. The archaeal 16S rRNA phylotypes were dominated by a single group of sequences that matched phylotypes reported from South African gold mines and possessed ammonia monooxygenase (amoA) genes. Both the phylogenetic and the mineral data show that acidic microenvironments play an important role in shale weathering, but the shale has a higher microbial diversity than previously described pyritic acid mine drainage sites. The presence of a potentially biogeochemically active microbial population on the rock surface suggests that microorganisms may contribute to early events of shale degradation and coastal erosion.

Vibro-acoustic condition monitoring of Internal Combustion Engines: A critical review of existing techniques

Science.gov (United States)

Delvecchio, S.; Bonfiglio, P.; Pompoli, F.

2018-01-01

This paper deals with the state-of-the-art strategies and techniques based on vibro-acoustic signals that can monitor and diagnose malfunctions in Internal Combustion Engines (ICEs) under both test bench and vehicle operating conditions. Over recent years, several authors have summarized what is known in critical reviews mainly focused on reciprocating machines in general or on specific signal processing techniques: no attempts to deal with IC engine condition monitoring have been made. This paper first gives a brief summary of the generation of sound and vibration in ICEs in order to place further discussion on fault vibro-acoustic diagnosis in context. An overview of the monitoring and diagnostic techniques described in literature using both vibration and acoustic signals is also provided. Different faulty conditions are described which affect combustion, mechanics and the aerodynamics of ICEs. The importance of measuring acoustic signals, as opposed to vibration signals, is due since the former seem to be more suitable for implementation on on-board monitoring systems in view of their non-intrusive behaviour, capability in simultaneously capturing signatures from several mechanical components and because of the possibility of detecting faults affecting airborne transmission paths. In view of the recent needs of the industry to (-) optimize component structural durability adopting long-life cycles, (-) verify the engine final status at the end of the assembly line and (-) reduce the maintenance costs monitoring the ICE life during vehicle operations, monitoring and diagnosing system requests are continuously growing up. The present review can be considered a useful guideline for test engineers in understanding which types of fault can be diagnosed by using vibro-acoustic signals in sufficient time in both test bench and operating conditions and which transducer and signal processing technique (of which the essential background theory is here reported) could be