WorldWideScience

Sample records for architecture reflects pluripotency

  1. A Declarative Approach to Architectural Reflection

    DEFF Research Database (Denmark)

    Ingstrup, Mads; Hansen, Klaus Marius

    2005-01-01

    Recent research shows runtime architectural reflection is instrumental in, for instance, building adaptive and flexible systems or checking correspondence between design and implementation. Moreover, experience with computational reflection in various branches of computer science shows that the...... interface through which the meta-information of the running system is accessed, and possibly modified, lies at the heart of designing reflective systems. This paper proposes that such an interface should be like a database: accessed through queries expressed using the concepts with which architecture is...... described. Specifically, our contributions are: (1) a presentation of the general idea of a query-based approach to architectural reflection, (2) a definition of an Architectural Query Language (AQL) in which perspectives on an architectural model can be expressed as queries, (3) a prototype of a system...

  2. Runtime software architecture based on reflective middleware

    Institute of Scientific and Technical Information of China (English)

    HUANG Gang; MEI Hong; YANG Fuqing

    2004-01-01

    There exists a consensus that software architecture (SA) plays a central role in software development and also plays an important role in the lifecycle phases after software delivery. Particularly, SA can be used to reduce the great difficulty and cost of software maintenance and evolution. In this paper, runtime software architecture (RSA) based on reflective middleware is proposed to support architecture-based software maintenance and evolution. In this approach, the actual states and behaviors of the runtime system can be observed and manipulated in a consistent and understandable way through its architectural view. Being an accurate, up-to-date, semantic and operable view of SA, RSA looks components and connectors as "white-box" entities to accurately and thoroughly describe the runtime system, extends traditional architecture description languages to formally describe itself and naturally inherit plentiful semantics in traditional views of SA, and utilizes reflective middleware to observe and manipulate the runtime system. In order to demonstrate the feasibility of this approach, a reflective J2EE application server, called PKUAS, is implemented to observe and manipulate the components, connectors and constraints in the runtime system. Finally, the performance evaluation proves that making RSA explicit and operable at runtime has little effect on the runtime system.

  3. Reflective Subjects in Kant and Architectural Design Education

    Science.gov (United States)

    Rawes, Peg

    2007-01-01

    In architectural design education, students develop drawing, conceptual, and critical skills which are informed by their ability to reflect upon the production of ideas in design processes and in the urban, environmental, social, historical, and cultural context that define architecture and the built environment. Reflective actions and thinking…

  4. Echo thresholds for reflections from acoustically diffusive architectural surfaces.

    Science.gov (United States)

    Robinson, Philip W; Walther, Andreas; Faller, Christof; Braasch, Jonas

    2013-10-01

    When sound reflects from an irregular architectural surface, it spreads spatially and temporally. Extensive research has been devoted to prediction and measurement of diffusion, but less has focused on its perceptual effects. This paper examines the effect of temporal diffusion on echo threshold. There are several notable differences between the waveform of a reflection identical to the direct sound and one from an architectural surface. The onset and offset are damped and the energy is spread in time; hence, the reflection response has a lower peak amplitude, and is decorrelated from the direct sound. The perceptual consequences of these differences are previously undocumented. Echo threshold tests are conducted with speech and music signals, using direct sound and a simulated reflection that is either identical to the direct sound or has various degrees of diffusion. Results indicate that for a speech signal, diffuse reflections are less easily detectable as a separate auditory event than specular reflections of the same total energy. For a music signal, no differences are observed between the echo thresholds for reflections with and without temporal diffusion. Additionally, echo thresholds are found to be shorter for speech than for music, and shorter for spatialized than for diotic presentation of signals. PMID:24116414

  5. Personality is reflected in the brain's intrinsic functional architecture.

    Directory of Open Access Journals (Sweden)

    Jonathan S Adelstein

    Full Text Available Personality describes persistent human behavioral responses to broad classes of environmental stimuli. Investigating how personality traits are reflected in the brain's functional architecture is challenging, in part due to the difficulty of designing appropriate task probes. Resting-state functional connectivity (RSFC can detect intrinsic activation patterns without relying on any specific task. Here we use RSFC to investigate the neural correlates of the five-factor personality domains. Based on seed regions placed within two cognitive and affective 'hubs' in the brain--the anterior cingulate and precuneus--each domain of personality predicted RSFC with a unique pattern of brain regions. These patterns corresponded with functional subdivisions responsible for cognitive and affective processing such as motivation, empathy and future-oriented thinking. Neuroticism and Extraversion, the two most widely studied of the five constructs, predicted connectivity between seed regions and the dorsomedial prefrontal cortex and lateral paralimbic regions, respectively. These areas are associated with emotional regulation, self-evaluation and reward, consistent with the trait qualities. Personality traits were mostly associated with functional connections that were inconsistently present across participants. This suggests that although a fundamental, core functional architecture is preserved across individuals, variable connections outside of that core encompass the inter-individual differences in personality that motivate diverse responses.

  6. Label-free characterization of living human induced pluripotent stem cells by subcellular topographic imaging technique using full-field quantitative phase microscopy coupled with interference reflection microscopy

    OpenAIRE

    Sugiyama, Norikazu; Asai, Yasuyuki; Yamauchi, Toyohiko; Kataoka, Takuji; Ikeda, Takahiro; Iwai, Hidenao; Sakurai, Takashi; Mizuguchi, Yoshinori

    2012-01-01

    There is a need for a noninvasive technique to monitor living pluripotent stem cell condition without any labeling. We present an optical imaging technique that is able to capture information about optical path difference through the cell and cell adhesion properties simultaneously using a combination of quantitative phase microscopy (QPM) and interference reflection microscopy (IRM) techniques. As a novel application of QPM and IRM, this multimodal imaging technique demonstrated its ability ...

  7. The influence of acoustic reflections from diffusive architectural surfaces on spatial auditory perception

    Science.gov (United States)

    Robinson, Philip W.

    This thesis addresses the effect of reflections from diffusive architectural surfaces on the perception of echoes and on auditory spatial resolution. Diffusive architectural surfaces play an important role in performance venue design for architectural expression and proper sound distribution. Extensive research has been devoted to the prediction and measurement of the spatial dispersion. However, previous psychoacoustic research on perception of reflections and the precedence effect has focused on specular reflections. This study compares the echo threshold of specular reflections, against those for reflections from realistic architectural surfaces, and against synthesized reflections that isolate individual qualities of reflections from diffusive surfaces, namely temporal dispersion and spectral coloration. In particular, the activation of the precedence effect, as indicated by the echo threshold is measured. Perceptual tests are conducted with direct sound, and simulated or measured reflections with varying temporal dispersion. The threshold for reflections from diffusive architectural surfaces is found to be comparable to that of a specular re ection of similar energy rather than similar amplitude. This is surprising because the amplitude of the dispersed re ection is highly attenuated, and onset cues are reduced. This effect indicates that the auditory system is integrating re ection response energy dispersed over many milliseconds into a single stream. Studies on the effect of a single diffuse reflection are then extended to a full architectural enclosure with various surface properties. This research utilizes auralizations from measured and simulated performance venues to investigate spatial discrimination of multiple acoustic sources in rooms. It is found that discriminating the lateral arrangement of two sources is possible at narrower separation angles when reflections come from at rather than diffusive surfaces. Additionally, subjective impressions are

  8. From Molecular Gastronomy to Molecular Architecture: Reflections towards a new architectural praxis

    OpenAIRE

    Rocha, Joao

    2011-01-01

    The relationship between architecture and research has been barely discussed and by making use of critical reading this paper proposes to investigate how other disciplines started to use Research and Development (R&D) as part of their creative processes. In particular it explores how gastronomy has unfolded new R&D paths through the revolutionary work of three leading chefs: Ferrian Adria, Rene Redzepi and Grant Achatz, illustrating the deep impact that the use of R&D had in this field and ho...

  9. Pluripotent Stamcelleforskning

    OpenAIRE

    Hersing, Daniel Green; Borhani, Pegah

    2009-01-01

    Research aimed at finding the ultimate cure for (until now incurable) diseases, is underway. The ability to cure diseases such as diabetes type 1, Parkinson's disease and others is perhaps in a not so distant future. The solution lies perhaps in pluripotent stem cells, which have the potential to develop into every cell type in the body. This project aims to provide an overview of the procurement methods available for pluripotent stem cells by examining the methods and what opportunities a...

  10. What Went Wrong? Reflections on the Condition of Architecture and Urbanism in Lebanon

    Directory of Open Access Journals (Sweden)

    Elie Haddad

    2012-11-01

    Full Text Available In a short article presented at a conference in New York City two years ago, Joan Ockman lucidly diagnosed the contemporary dilemma faced by architecture, i.e. how to insert itself between a pessimistic discourse that warns of the end of time, and an uncritical surrender to globalization. This dilemma is now universal(i. It applies to New York City, where in the same context Kenneth Frampton commented on the dystopia of an “oddly paranoid, rather ruthless, instrumental and resentful landscape”(ii, as well as to other cities around the world, especially in the Third World, where more difficult conditions permeate architectural practice, resulting in even more devastated landscapes. This article will discuss issues that relate to architectural practice and pedagogy, drawing on specific examples in the context of Beirut, Lebanon, and reflecting on the impact of‘architectural education’ and the transformations within the architectural profession in this context. One can no longer deny the negative impact of economics on a profession that has been, for the most part, idealistic in its approach to the built environment, but the responsibility of architects and architectural education, can no longer beminimized in assessing the problems that cities like Beirut face today. i The conference was organized at Columbia University, andpublished as The State of Architecture at the Beginning of the21st Century, New York: Monacelli Press, 2003. See JoanOckman’s “Criticism in the Age of Globalization” [78-9]ii “Brief Reflections on the Predicament of Urbanism” , ibidem[13

  11. Estimation of vegetation LAI from hyperspectral reflectance data: Effects of soil type and plant architecture

    Science.gov (United States)

    Darvishzadeh, Roshanak; Skidmore, Andrew; Atzberger, Clement; van Wieren, Sip

    2008-09-01

    The retrieval of canopy biophysical variables is known to be affected by confounding factors such as plant type and background reflectance. The effects of soil type and plant architecture on the retrieval of vegetation leaf area index (LAI) from hyperspectral data were assessed in this study. In situ measurements of LAI were related to reflectances in the red and near-infrared and also to five widely used spectral vegetation indices (VIs). The study confirmed that the spectral contrast between leaves and soil background determines the strength of the LAI-reflectance relationship. It was shown that within a given vegetation species, the optimum spectral regions for LAI estimation were similar across the investigated VIs, indicating that the various VIs are basically summarizing the same spectral information for a given vegetation species. Cross-validated results revealed that, narrow-band PVI was less influenced by soil background effects (0.15 ≤ RMSE cv ≤ 0.56). The results suggest that, when using remote sensing VIs for LAI estimation, not only is the choice of VI of importance but also prior knowledge of plant architecture and soil background. Hence, some kind of landscape stratification is required before using hyperspectral imagery for large-scale mapping of vegetation biophysical variables.

  12. Remotely amplified combined ring-tree dense access network architecture using reflective RSOA-based ONU

    Science.gov (United States)

    Lazaro, Jose A.; Bock, Carlos; Polo, Victor; Martinez, Reynaldo I.; Prat, Josep

    2007-06-01

    A highly scalable access architecture achieving high density and featuring resiliency, centralized light-generation control, remote amplification, and colorless optical network unit with reflective semiconductor optical amplifier (RSOA) for upstream modulation is presented and experimentally demonstrated. It is based on a user-single-fiber completely passive outside plant and provides broadband connections to >1000 users distributed along large distances. It is believed to represent an intermediate step toward metro-access convergence and offers flexible configurations covering high- and low-density population areas.

  13. Reflections on architectural design education: The return of rationalism in the studio

    Directory of Open Access Journals (Sweden)

    Fathi Bashier

    2014-12-01

    The Department of Architecture and Urban Planning at the Ethiopian Institute of Technology EiT of Mekelle University (MU is currently developing a research program in which the development of and reflection on design methods is a key research area. Within this framework, the present study is intends to be an introductory effort to guide future empirical research. The present study aims to describe the design process of architects, and introduces theoretical and technical frameworks. The integrated design paradigm as a system of inquiry within the spatial relationship strategy is framed.

  14. Reflections on architectural design education: The return of rationalism in the studio

    OpenAIRE

    Fathi Bashier

    2014-01-01

    The design studio environment has remained the same throughout the past century. As the Studio Culture Task Force of the American Institute of Architecture Students (AIAS) (Koch et al., 2006) noted, the ongoing changes in architecture education are not aligned with today׳s fast-changing world, especially in the context of architectural practice. The AIAS analyzed the design studio problem and expressed doubts on the effectiveness of current studio practices in providing adequate design-thinki...

  15. Morphology of muscle attachment sites in the modern human hand does not reflect muscle architecture.

    Science.gov (United States)

    Williams-Hatala, E M; Hatala, K G; Hiles, S; Rabey, K N

    2016-01-01

    Muscle attachment sites (entheses) on dry bones are regularly used by paleontologists to infer soft tissue anatomy and to reconstruct behaviors of extinct organisms. This method is commonly applied to fossil hominin hand bones to assess their abilities to participate in Paleolithic stone tool behaviors. Little is known, however, about how or even whether muscle anatomy and activity regimes influence the morphologies of their entheses, especially in the hand. Using the opponens muscles from a sample of modern humans, we tested the hypothesis that aspects of hand muscle architecture that are known to be influenced by behavior correlate with the size and shape of their associated entheses. Results show no consistent relationships between these behaviorally-influenced aspects of muscle architecture and entheseal morphology. Consequently, it is likely premature to infer patterns of behavior, such as stone tool making in fossil hominins, from these same entheses. PMID:27334440

  16. Evidence-based design: theoretical and practical reflections of an emerging approach in office architecture

    OpenAIRE

    Sailer, K.; Budgen, A.; Lonsdale, N; Turner, A.; A Penn

    2008-01-01

    Evidence-based design is a practice that has emerged only relatively recently, inspired by a growing popularity of evidence-based approaches in other professions such as medicine. It has received greatest attention in design for the health sector, but has received less in office architecture, although this would seem not only to be beneficial for clients, but increasingly important in a changing business environment. This paper outlines the history and origins of evidence-based practice, its ...

  17. Pluripotent stem cell lines

    OpenAIRE

    Yu, Junying; Thomson, James A.

    2008-01-01

    The derivation of human embryonic stem cells 10 years ago ignited an explosion of public interest in stem cells, yet this achievement depended on prior decades of research on mouse embryonic carcinoma cells and embryonic stem cells. In turn, the recent derivation of mouse and human induced pluripotent stem cells depended on the prior studies on mouse and human embryonic stem cells. Both human embryonic stem cells and induced pluripotent stem cells can self-renew indefinitely in vitro while ma...

  18. Vital architecture, slow momentum policy

    DEFF Research Database (Denmark)

    Braae, Ellen Marie

    2010-01-01

    A reflection on the relation between Danish landscape architecture policy and the statements made through current landscape architectural project.......A reflection on the relation between Danish landscape architecture policy and the statements made through current landscape architectural project....

  19. Electroactive semi-interpenetrating polymer networks architecture with tunable IR reflectivity

    Science.gov (United States)

    Chevrot, C.; Teyssié, D.; Verge, P.; Goujon, L.; Tran-Van, F.; Vidal, F.; Aubert, P. H.; Peralta, S.; Sauques, L.

    2011-04-01

    A promising alternative of multi-layered devices showing electrochromic properties results from the design of a self-supported semi-interpenetrating polymer network (semi-IPN) including an electronic conductive polymer (ECP) formed within. The formation of the ECP in the network has already been described by oxidative polymerization using iron trichloride as an oxidant and leading to conducting semi-IPN with mixed electronic and ionic conductivities as well as convenient mechanical properties. This presentation relates to the elaboration of such semi-IPN using polyethyleneoxide (PEO) network or a PEO/NBR (Nitrile Butadiene Rubber) IPN in which a linear poly (3,4-ethylenedioxythiophene) (PEDOT) is formed symmetrically and selectively as very thin layers very next to the two main faces of the film matrix. PEO/PEDOT semi-IPNs lead to interesting optical reflective properties in the IR between 0.8 and 25 μm. Reflectance contrasts up to 35 % is observed when, after swelling in an ionic liquid, a low voltage is applied between the two main faces of the film. However the low flexibility and brittleness of the film and a slow degradation in air at temperature up from 60°C prompted to replace the PEO matrix by a flexible PEO/NBR IPN one. Indeed, the combination of NBR and PEO in an IPN leads to materials possessing flexible properties, good ionic conductivity at 25°C as well as a better resistance to thermal ageing. Finally, NBR/PEO/PEDOT semi-IPNs allow observing comparable reflectance contrast in the IR range than those shown by PEO/PEDOT semi-IPNs.

  20. Seismic architecture of the Chalk Group from onshore reflection data in eastern Denmark

    DEFF Research Database (Denmark)

    Moreau, Julien; Anderskouv, Kresten; Boldreel, Lars Ole;

    The Upper Cretaceous-Danian chalk is well exposed in the 14 km long coastal cliff of Stevns Klint (eastern Denmark). The cliff is a world renowned for its spectacular exposure of the Cretaceous-Palaeogene boundary. Based on regional geological knowledge of the field and cores, the characteristics...... completed with the acquisition of an extensive set of subsurface data. The data include high resolution 2D multichannel seismics onshore and offshore, a seismic refraction profile, two entirely cored boreholes including wireline logs, GPR cross-hole tomography, thermographic analysis, etc. We intend...... to compile and merge the geological and geophysical datasets to investigate the variation of the Chalk Group properties and their signature in the subsurface. In this communication, the seismic reflection data are being analysed. Very high resolution litho-, bio- and cyclostratigraphy can be correlated...

  1. Induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    Siddhartha Bhowmik; LI Yong

    2011-01-01

    Induced pluripotent stem (iPS) cells are a recent development which has brought a promise of great therapeutic values. The previous technique of somatic cell nuclear transfer (SCNT) has been ineffective in humans. Recent discoveries show that human fibroblasts can be reprogrammed by a transient over expression of a small number of genes; they can undergo induced pluripotency. iPS were first produced in 2006. By 2008, work was underway to remove the potential oncogenes from their structure. In 2009, protein iPS (piPS) cells were discovered. Surface markers and reporter genes play an important role in stem cell research. Clinical applications include generation of self renewing stem cells, tissue replacement and many more. Stem cell therapy has the ability to dramatically change the treatment of human diseases.

  2. The Architecture of Iron Microbial Mats Reflects the Adaptation of Chemolithotrophic Iron Oxidation in Freshwater and Marine Environments

    OpenAIRE

    Chan, Clara S.; McAllister, Sean M.; Leavitt, Anna H.; Brian T. Glazer; Krepski, Sean T.; Emerson, David

    2016-01-01

    Microbes form mats with architectures that promote efficient metabolism within a particular physicochemical environment, thus studying mat structure helps us understand ecophysiology. Despite much research on chemolithotrophic Fe-oxidizing bacteria, Fe mat architecture has not been visualized because these delicate structures are easily disrupted. There are striking similarities between the biominerals that comprise freshwater and marine Fe mats, made by Beta- and Zetaproteobacteria, respecti...

  3. Reflection on Full Life Cycle Green Architectural Design of Passive Priority---Taking the Award Design of China Merchants Property 2013 Green Architectural Design Competition as an Example

    Institute of Scientific and Technical Information of China (English)

    ZhenHe Fan; Yan Qiao

    2014-01-01

    In the China merchants property 2013 green architectural design competition, feature of this award-winning program is the design method based on the principles of passive priority and comprehensive utilization of full life cycle. The passive priority can be achieved by building form derived from the simulation and analysis of wind environment, improvement of the building envelope insulation and the dehumidification of fresh air, the use of solar energy. The full life cycle utilization can be accomplished by the combination of exhibition and residents’ leisure activities, and the integration with local cultural tradition, thereby improving energy efficiency and the utilization of the building.

  4. Fishing Pluripotency Mechanisms In Vivo

    Directory of Open Access Journals (Sweden)

    Ana V. Sánchez-Sánchez, Esther Camp, José L. Mullor

    2011-01-01

    Full Text Available To understand the molecular mechanisms that regulate the biology of embryonic stem cells (ESCs it is necessary to study how they behave in vivo in their natural environment. It is particularly important to study the roles and interactions of the different proteins involved in pluripotency and to use this knowledge for therapeutic purposes. The recent description of key pluripotency factors like Oct4 and Nanog in non-mammalian species has introduced other animal models, such as chicken, Xenopus, zebrafish and medaka, to the study of pluripotency in vivo. These animal models complement the mouse model and have provided new insights into the evolution of Oct4 and Nanog and their different functions during embryonic development. Furthermore, other pluripotency factors previously identified in teleost fish such as Klf4, STAT3, Sox2, telomerase and Tcf3 can now be studied in the context of a functional pluripotency network. The many experimental advantages of fish will fuel rapid analysis of the roles of pluripotency factors in fish embryonic development and the identification of new molecules and mechanisms governing pluripotency.

  5. Looking back on 10 years of the ATLAS Metadata Interface. Reflections on architecture, code design and development methods

    International Nuclear Information System (INIS)

    The 'ATLAS Metadata Interface' framework (AMI) has been developed in the context of ATLAS, one of the largest scientific collaborations. AMI can be considered to be a mature application, since its basic architecture has been maintained for over 10 years. In this paper we describe briefly the architecture and the main uses of the framework within the experiment (TagCollector for release management and Dataset Discovery). These two applications, which share almost 2000 registered users, are superficially quite different, however much of the code is shared and they have been developed and maintained over a decade almost completely by the same team of 3 people. We discuss how the architectural principles established at the beginning of the project have allowed us to continue both to integrate the new technologies and to respond to the new metadata use cases which inevitably appear over such a time period.

  6. Expression of acyl-CoA synthetase 5 reflects the state of villus architecture in human small intestine

    DEFF Research Database (Denmark)

    Gassler, Nikolaus; Kopitz, Jürgen; Tehrani, Arman;

    2004-01-01

    -CoA synthetase 5 pattern correlate with conversion of intestinal epithelial cells to a gastric phenotype. These results suggest that deranged acyl-CoA synthetase 5 expression, synthesis, and activity are closely related to the state of villus architecture and epithelial homeostasis in human small intestine.......Several disorders of the small intestine are associated with disturbances in villus architecture. Thus, an understanding of the molecular mechanisms associated with the differentiation of villi represents an important step in the improvement of the understanding of small intestinal pathology...

  7. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles to...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  8. Architectural technology

    DEFF Research Database (Denmark)

    2005-01-01

    The booklet offers an overall introduction to the Institute of Architectural Technology and its projects and activities, and an invitation to the reader to contact the institute or the individual researcher for further information. The research, which takes place at the Institute of Architectural...... Technology at the Roayl Danish Academy of Fine Arts, School of Architecture, reflects a spread between strategic, goal-oriented pilot projects, commissioned by a ministry, a fund or a private company, and on the other hand projects which originate from strong personal interests and enthusiasm of individual...

  9. The architecture of iron microbial mats reflects the adaptation of chemolithotrophic iron oxidation in freshwater and marine environments

    Directory of Open Access Journals (Sweden)

    Clara S Chan

    2016-06-01

    Full Text Available Microbes form mats with architectures that promote efficient metabolism within a particular physicochemical environment, thus studying mat structure helps us understand ecophysiology. Despite much research on chemolithotrophic Fe-oxidizing bacteria, Fe mat architecture has not been visualized because these delicate structures are easily disrupted. There are striking similarities between the biominerals that comprise freshwater and marine Fe mats, made by Beta- and Zetaproteobacteria, respectively. If these biominerals are assembled into mat structures with similar functional morphology, this would suggest that mat architecture is adapted to serve roles specific to Fe oxidation. To evaluate this, we combined light, confocal, and scanning electron microscopy of intact Fe microbial mats with experiments on sheath formation in culture, in order to understand mat developmental history and subsequently evaluate the connection between Fe oxidation and mat morphology. We sampled a freshwater sheath mat from Maine and marine stalk and sheath mats from Loihi Seamount hydrothermal vents, Hawaii. Mat morphology correlated to niche: stalks formed in steeper O2 gradients while sheaths were associated with low to undetectable O2 gradients. Fe-biomineralized filaments, twisted stalks or hollow sheaths, formed the highly porous framework of each mat. The mat-formers are keystone species, with nascent marine stalk-rich mats comprised of novel and uncommon Zetaproteobacteria. For all mats, filaments were locally highly parallel with similar morphologies, indicating that cells were synchronously tracking a chemical or physical cue. In the freshwater mat, cells inhabited sheath ends at the growing edge of the mat. Correspondingly, time lapse culture imaging showed that sheaths are made like stalks, with cells rapidly leaving behind an Fe oxide filament. The distinctive architecture common to all observed Fe mats appears to serve specific functions related to

  10. The Architecture of Iron Microbial Mats Reflects the Adaptation of Chemolithotrophic Iron Oxidation in Freshwater and Marine Environments

    Science.gov (United States)

    Chan, Clara S.; McAllister, Sean M.; Leavitt, Anna H.; Glazer, Brian T.; Krepski, Sean T.; Emerson, David

    2016-01-01

    Microbes form mats with architectures that promote efficient metabolism within a particular physicochemical environment, thus studying mat structure helps us understand ecophysiology. Despite much research on chemolithotrophic Fe-oxidizing bacteria, Fe mat architecture has not been visualized because these delicate structures are easily disrupted. There are striking similarities between the biominerals that comprise freshwater and marine Fe mats, made by Beta- and Zetaproteobacteria, respectively. If these biominerals are assembled into mat structures with similar functional morphology, this would suggest that mat architecture is adapted to serve roles specific to Fe oxidation. To evaluate this, we combined light, confocal, and scanning electron microscopy of intact Fe microbial mats with experiments on sheath formation in culture, in order to understand mat developmental history and subsequently evaluate the connection between Fe oxidation and mat morphology. We sampled a freshwater sheath mat from Maine and marine stalk and sheath mats from Loihi Seamount hydrothermal vents, Hawaii. Mat morphology correlated to niche: stalks formed in steeper O2 gradients while sheaths were associated with low to undetectable O2 gradients. Fe-biomineralized filaments, twisted stalks or hollow sheaths, formed the highly porous framework of each mat. The mat-formers are keystone species, with nascent marine stalk-rich mats comprised of novel and uncommon Zetaproteobacteria. For all mats, filaments were locally highly parallel with similar morphologies, indicating that cells were synchronously tracking a chemical or physical cue. In the freshwater mat, cells inhabited sheath ends at the growing edge of the mat. Correspondingly, time lapse culture imaging showed that sheaths are made like stalks, with cells rapidly leaving behind an Fe oxide filament. The distinctive architecture common to all observed Fe mats appears to serve specific functions related to chemolithotrophic Fe

  11. The transcriptional regulation of pluripotency

    Institute of Scientific and Technical Information of China (English)

    Jia-Chi Yeo; Huck-Hui Ng

    2013-01-01

    The defining features of embryonic stem cells (ESCs) are their self-renewing and pluripotent capacities.Indeed,the ability to give rise into all cell types within the organism not only allows ESCs to function as an ideal in vitro tool to study embryonic development,but also offers great therapeutic potential within the field of regenerative medicine.However,it is also this same remarkable developmental plasticity that makes the efficient control of ESC differentiation into the desired cell type very difficult.Therefore,in order to harness ESCs for clinical applications,a detailed understanding of the molecular and cellular mechanisms controlling ESC pluripotency and lineage commitment is necessary.In this respect,through a variety of transcriptomic approaches,ESC pluripotency has been found to be regulated by a system of ESC-associated transcription factors; and the external signalling environment also acts as a key factor in modulating the ESC transcriptome.Here in this review,we summarize our current understanding of the transcriptional regulatory network in ESCs,discuss how the control of various signalling pathways could influence pluripotency,and provide a future outlook of ESC research.

  12. Pluripotency and its layers of complexity

    Directory of Open Access Journals (Sweden)

    Ooi Jolene

    2012-09-01

    Full Text Available Abstract Pluripotency is depicted by a self-renewing state that can competently differentiate to form the three germ layers. Different stages of early murine development can be captured on a petri dish, delineating a spectrum of pluripotent states, ranging from embryonic stem cells, embryonic germ cells to epiblast stem cells. Anomalous cell populations displaying signs of pluripotency have also been uncovered, from the isolation of embryonic carcinoma cells to the derivation of induced pluripotent stem cells. Gaining insight into the molecular circuitry within these cell types enlightens us about the significance and contribution of each stage, hence deepening our understanding of vertebrate development. In this review, we aim to describe experimental milestones that led to the understanding of embryonic development and the conception of pluripotency. We also discuss attempts at exploring the realm of pluripotency with the identification of pluripotent stem cells within mouse teratocarcinomas and embryos, and the generation of pluripotent cells through nuclear reprogramming. In conclusion, we illustrate pluripotent cells derived from other organisms, including human derivatives, and describe current paradigms in the comprehension of human pluripotency.

  13. Architectural Engineers

    DEFF Research Database (Denmark)

    Petersen, Rikke Premer

    engineering is addresses from two perspectives – as an educational response and an occupational constellation. Architecture and engineering are two of the traditional design professions and they frequently meet in the occupational setting, but at educational institutions they remain largely estranged. The...... paper builds on a multi-sited study of an architectural engineering program at the Technical University of Denmark and an architectural engineering team within an international engineering consultancy based on Denmark. They are both responding to new tendencies within the building industry where the...... role of engineers and architects increasingly overlap during the design process, but their approaches reflect different perceptions of the consequences. The paper discusses some of the challenges that design education, not only within engineering, is facing today: young designers must be equipped with...

  14. Advances in reprogramming to pluripotency.

    Science.gov (United States)

    Alateeq, Suad; Fortuna, Patrick R J; Wolvetang, Ernst

    2015-01-01

    Pluripotent stem cells (PSCs) derived from somatic cells represent a powerful experimental tool for investigating the molecular mechanisms underlying the disease phenotype; with prospects to advance medical therapies. They also have significant potential as a renewable source of autologous cells for cellular therapy. Various approaches for PSC derivation from somatic cells have been reported in the literature. The method used for reprogramming is particularly relevant as it may affect the characteristics and quality of PSCs. This review will present an overview of the basic strategies and methods for reprogramming to pluripotency. These strategies will be briefly discussed in the context of how the mechanism of reprogramming could influence PSC characteristics with respect to safety and quality. Aspects of the reprogramming approach that can influence PSC properties, such as culture conditions and donor cell source, are also discussed. PMID:25697500

  15. Reprogrammed Pluripotent Stem Cells from Somatic Cells

    OpenAIRE

    Kim, Jong Soo; Choi, Hyun Woo; Choi, Sol; Do, Jeong Tae

    2011-01-01

    Pluripotent stem cells, such as embryonic stem (ES) cells, can differentiate into all cell types. So, these cells can be a biological resource for regenerative medicine. However, ES cells known as standard pluripotent cells have problem to be used for cell therapy because of ethical issue of the origin and immune response on the graft. Hence, recently reprogrammed pluripotent cells have been suggested as an alternative source for regenerative medicine. Somatic cells can acquire the ES cell-li...

  16. Software Architecture: Architecture Constraints

    OpenAIRE

    Tibermacine, Chouki

    2014-01-01

    International audience In this chapter, we introduce an additional, yet essential, concept in describing software architectures : architecture constraints. We explain the precise role of these entities and their importance in object-oriented, component-based or service-oriented software engi-neering. We then describe the way in which they are specified and interpreted. An architect can define architecture constraints and then associate them to architectural descriptions to limit their stru...

  17. Epigenetic Biomarker to Support Classification into Pluripotent and Non-Pluripotent Cells

    Science.gov (United States)

    Lenz, Michael; Goetzke, Roman; Schenk, Arne; Schubert, Claudia; Veeck, Jürgen; Hemeda, Hatim; Koschmieder, Steffen; Zenke, Martin; Schuppert, Andreas; Wagner, Wolfgang

    2015-03-01

    Quality control of human induced pluripotent stem cells (iPSCs) can be performed by several methods. These methods are usually relatively labor-intensive, difficult to standardize, or they do not facilitate reliable quantification. Here, we describe a biomarker to distinguish between pluripotent and non-pluripotent cells based on DNA methylation (DNAm) levels at only three specific CpG sites. Two of these CpG sites were selected by their discriminatory power in 258 DNAm profiles - they were either methylated in pluripotent or non-pluripotent cells. The difference between these two β-values provides an Epi-Pluri-Score that was validated on independent DNAm-datasets (264 pluripotent and 1,951 non-pluripotent samples) with 99.9% specificity and 98.9% sensitivity. This score was complemented by a third CpG within the gene POU5F1 (OCT4), which better demarcates early differentiation events. We established pyrosequencing assays for the three relevant CpG sites and thereby correctly classified DNA of 12 pluripotent cell lines and 31 non-pluripotent cell lines. Furthermore, DNAm changes at these three CpGs were tracked in the course of differentiation of iPSCs towards mesenchymal stromal cells. The Epi-Pluri-Score does not give information on lineage-specific differentiation potential, but it provides a simple, reliable, and robust biomarker to support high-throughput classification into either pluripotent or non-pluripotent cells.

  18. Architecture on Architecture

    DEFF Research Database (Denmark)

    Olesen, Karen

    2016-01-01

    how recognising the autonomy of architecture, not as an esoteric concept but as a valid source of information in a pragmatic design practice, may help us overcome the often-proclaimed dichotomy between formal autonomy and a societally committed architecture. It follows that in architectural education...

  19. The pluripotency factor Nanog regulates pericentromeric heterochromatin organization in mouse embryonic stem cells.

    Science.gov (United States)

    Novo, Clara Lopes; Tang, Calvin; Ahmed, Kashif; Djuric, Ugljesa; Fussner, Eden; Mullin, Nicholas P; Morgan, Natasha P; Hayre, Jasvinder; Sienerth, Arnold R; Elderkin, Sarah; Nishinakamura, Ryuichi; Chambers, Ian; Ellis, James; Bazett-Jones, David P; Rugg-Gunn, Peter J

    2016-05-01

    An open and decondensed chromatin organization is a defining property of pluripotency. Several epigenetic regulators have been implicated in maintaining an open chromatin organization, but how these processes are connected to the pluripotency network is unknown. Here, we identified a new role for the transcription factor NANOG as a key regulator connecting the pluripotency network with constitutive heterochromatin organization in mouse embryonic stem cells. Deletion of Nanog leads to chromatin compaction and the remodeling of heterochromatin domains. Forced expression of NANOG in epiblast stem cells is sufficient to decompact chromatin. NANOG associates with satellite repeats within heterochromatin domains, contributing to an architecture characterized by highly dispersed chromatin fibers, low levels of H3K9me3, and high major satellite transcription, and the strong transactivation domain of NANOG is required for this organization. The heterochromatin-associated protein SALL1 is a direct cofactor for NANOG, and loss of Sall1 recapitulates the Nanog-null phenotype, but the loss of Sall1 can be circumvented through direct recruitment of the NANOG transactivation domain to major satellites. These results establish a direct connection between the pluripotency network and chromatin organization and emphasize that maintaining an open heterochromatin architecture is a highly regulated process in embryonic stem cells. PMID:27125671

  20. Quantifying Reflection

    DEFF Research Database (Denmark)

    Alcock, Gordon Lindsay

    2013-01-01

    This paper documents 1st semester student reflections on “learning to learn” in a team-based PBL environment with quantitative and qualitative student reflective feedback on the learning gains of 60 Architectural Technology and Construction Management students at VIA University College, Denmark. It...... contrasts the students’ self-assessment in a range of ‘product’ skills such as Revit, Structural Design, Mathematics of construction, Technical Installations; as well as ‘process’ competencies such as ‘Working in a team’, Sharing knowledge, Maintaining a portfolio and Reflecting ON learning and FOR learning...

  1. Reprogrammed pluripotent stem cells from somatic cells.

    Science.gov (United States)

    Kim, Jong Soo; Choi, Hyun Woo; Choi, Sol; Do, Jeong Tae

    2011-06-01

    Pluripotent stem cells, such as embryonic stem (ES) cells, can differentiate into all cell types. So, these cells can be a biological resource for regenerative medicine. However, ES cells known as standard pluripotent cells have problem to be used for cell therapy because of ethical issue of the origin and immune response on the graft. Hence, recently reprogrammed pluripotent cells have been suggested as an alternative source for regenerative medicine. Somatic cells can acquire the ES cell-like pluripotency by transferring somatic cell nuclei into oocytes, by cell fusion with pluripotent cells. Retroviral-mediated introduction of four factors, Oct4, Sox2, Klf4 and c-Myc can successfully reprogram somatic cells into ES cell-like pluripotent stem cells, known as induced pluripotent stem (iPS) cells. These cells closely resemble ES cells in gene expression pattern, cell biologic and phenotypic characteristics. However, to reach the eventual goal of clinical application, it is necessary to overcome the major drawbacks such as low reprogramming efficiency and genomic alterations due to viral integration. In this review, we discuss the current reprogramming techniques and mechanisms of nuclear reprogramming induced by transcription factor transduction. PMID:24298328

  2. nduced pluripotent stem cells and cell therapy

    Directory of Open Access Journals (Sweden)

    Banu İskender

    2013-12-01

    Full Text Available Human embryonic stem cells are derived from the inner cell mass of a blastocyst-stage embryo. They hold a huge promise for cell therapy with their self-renewing ability and pluripotency, which is known as the potential to differentiate into all cell types originating from three embryonic germ layers. However, their unique pluripotent feature could not be utilised for therapeutic purposes due to the ethical and legal problems during derivation. Recently, it was shown that the cells from adult tissues could be reverted into embryonic state, thereby restoring their pluripotent feature. This has strenghtened the possiblity of directed differentition of the reprogrammed somatic cells into the desired cell types in vitro and their use in regenerative medicine. Although these cells were termed as induced pluripotent cells, the mechanism of pluripotency has yet to be understood. Still, induced pluripotent stem cell technology is considered to be significant by proposing novel approaches in disease modelling, drug screening and cell therapy. Besides their self-renewing ability and their potential to differentiate into all cell types in a human body, they arouse a great interest in scientific world by being far from the ethical concerns regarding their embryonic counterparts and their unique feature of being patient-specific in prospective cell therapies. In this review, induced pluripotent stem cell technology and its role in cell-based therapies from past to present will be discussed. J Clin Exp Invest 2013; 4 (4: 550-561

  3. [The alchemy--epigenetic regulation of pluripotency].

    Science.gov (United States)

    Bem, Joanna; Grabowska, Iwona

    2013-01-01

    Embryonic stem cells (ESCs) self renew their population, also they are pluripotent which means they can differentiate into any given cell type. In specific culture conditions they remain undifferentiated. On the cellular level pluripotency is determined by many transcription factors, e.g. Sox2, Nanog, Klf4, Oct4. Epigenetic regulation is also crucial for both self renewal and pluripotency. This review focuses on epigenetic mechanisms, among them DNA methylation, posttranslational histone modifications, ATP dependent chromatin remodeling and miRNAs interactions. These mechanisms affect embryonic stem cells functions keeping them poised for differentiation. PMID:24044279

  4. Glycosyltransferase ST6GAL1 contributes to the regulation of pluripotency in human pluripotent stem cells

    OpenAIRE

    Yu-Chieh Wang; Jason W. Stein; Lynch, Candace L; Tran, Ha T.; Chia-Yao Lee; Ronald Coleman; Adam Hatch; Antontsev, Victor G.; Chy, Hun S.; O’Brien, Carmel M.; Shashi K. Murthy; Laslett, Andrew L.; Peterson, Suzanne E; Loring, Jeanne F

    2015-01-01

    Many studies have suggested the significance of glycosyltransferase-mediated macromolecule glycosylation in the regulation of pluripotent states in human pluripotent stem cells (hPSCs). Here, we observed that the sialyltransferase ST6GAL1 was preferentially expressed in undifferentiated hPSCs compared to non-pluripotent cells. A lectin which preferentially recognizes α-2,6 sialylated galactosides showed strong binding reactivity with undifferentiated hPSCs and their glycoproteins, and did so ...

  5. Architecture on Architecture

    DEFF Research Database (Denmark)

    Olesen, Karen

    2016-01-01

    This paper will discuss the challenges faced by architectural education today. It takes as its starting point the double commitment of any school of architecture: on the one hand the task of preserving the particular knowledge that belongs to the discipline of architecture, and on the other hand...... the obligation to prepare students to perform in a profession that is largely defined by forces outside that discipline. It will be proposed that the autonomy of architecture can be understood as a unique kind of information: as architecture’s self-reliance or knowledge-about itself. A knowledge that...... is not scientific or academic but is more like a latent body of data that we find embedded in existing works of architecture. This information, it is argued, is not limited by the historical context of the work. It can be thought of as a virtual capacity – a reservoir of spatial configurations that...

  6. Pluripotent Stem Cells and Gene Therapy

    OpenAIRE

    Simara, Pavel; Motl, Jason A.; Kaufman, Dan S.

    2013-01-01

    Human pluripotent stem cells represent an accessible cell source for novel cell-based clinical research and therapies. With the realization of induced pluripotent stem cells (iPSCs), it is possible to produce almost any desired cell type from any patient's cells. Current developments in gene modification methods have opened the possibility for creating genetically corrected human iPSCs for certain genetic diseases that could be used later in autologous transplantation. Promising preclinical s...

  7. Telomere regulation in pluripotent stem cells

    OpenAIRE

    Huang, Yan; Liang, Puping; Liu, Dan; Huang, Junjiu; Songyang, Zhou

    2014-01-01

    Pluripotent stem cells (PSCs) have the potential to produce any types of cells from all three basic germ layers and the capacity to self-renew and proliferate indefinitely in vitro. The two main types of PSCs, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), share common features such as colony morphology, high expression of Oct4 and Nanog, and strong alkaline phosphatase activity. In recent years, increasing evidences suggest that telomere length represents another imp...

  8. Generation of rabbit pluripotent stem cell lines

    OpenAIRE

    Tancos, Z.; Nemes, C.; Polgar, Z.; Gocza, E; Daniel, N; Stout, T. A. E.; P. Maraghechi; Pirity, M.K.; Osteil, P.; Tapponnier, Y.; Markossian, S.; Godet, M.; Afanassieff, M.; Bosze, Z.; Duranthon, V

    2012-01-01

    Pluripotent stem cells have the capacity to divide indefinitely and to differentiate into all somatic cells and tissue lines. They can be genetically manipulated in vitro by knocking genes in or out, and therefore serve as an excellent tool for gene function studies and for the generation of models for some human diseases. Since 1981, when the first mouse embryonic stem cell (ESC) line was generated, many attempts have been made to generate pluripotent stem cell lines from other species. Comp...

  9. Generation of functional eyes from pluripotent cells.

    Directory of Open Access Journals (Sweden)

    Andrea S Viczian

    2009-08-01

    Full Text Available Pluripotent cells such as embryonic stem (ES and induced pluripotent stem (iPS cells are the starting point from which to generate organ specific cell types. For example, converting pluripotent cells to retinal cells could provide an opportunity to treat retinal injuries and degenerations. In this study, we used an in vivo strategy to determine if functional retinas could be generated from a defined population of pluripotent Xenopus laevis cells. Animal pole cells isolated from blastula stage embryos are pluripotent. Untreated, these cells formed only epidermis, when transplanted to either the flank or eye field. In contrast, misexpression of seven transcription factors induced the formation of retinal cell types. Induced retinal cells were committed to a retinal lineage as they formed eyes when transplanted to the flanks of developing embryos. When the endogenous eye field was replaced with induced retinal cells, they formed eyes that were molecularly, anatomically, and electrophysiologically similar to normal eyes. Importantly, induced eyes could guide a vision-based behavior. These results suggest the fate of pluripotent cells may be purposely altered to generate multipotent retinal progenitor cells, which differentiate into functional retinal cell classes and form a neural circuitry sufficient for vision.

  10. The Matrix Regained: Reflections on the Use of the Grid in the Architectural Theories of Nicolaus Goldmann and Jean-Nicolas-Louis Durand

    Directory of Open Access Journals (Sweden)

    Jeroen Goudeau

    2015-05-01

    Full Text Available In addition to the superficial visual similarities between the architectural theories of the Silesian-born, seventeenth-century Dutch mathematician Nicolaus Goldmann and the early nineteenth-century French architect Jean-Nicolas-Louis Durand, there is a more profound interconnection: their use of the grid. This article evaluates the relation between the two theories and argues how Durand could have been influenced by Goldmann’s writings. It turns out to be more than likely that the two were linked by Durand´s German pupils who brought the tradition of German eighteenth-century architectural theory with them. This corpus was nourished by Leonhard Christoph Sturm´s ‘Goldmannic’ architecture.

  11. Defining the nature of human pluripotent stem cell progeny

    Institute of Scientific and Technical Information of China (English)

    Michaela Patterson; David N Chan; Iris Ha; Dana Case; Yongyan Cui; Ben Van Handel; Hanna KA Mikkola; William E Lowry

    2012-01-01

    While it is clear that human pluripotent stem cells (hPSCs) can differentiate to generate a panoply of various cell types,it is unknown how closely in vitro development mirrors that which occurs in vivo.To determine whether human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) make equivalent progeny,and whether either makes cells that are analogous to tissue-derived cells,we performed comprehensive transcriptome profiling of purified PSC derivatives and their tissue-derived counterparts.Expression profiling demonstrated that hESCs and hiPSCs make nearly identical progeny for the neural,hepatic,and mesenchymal lineages,and an absence of re-expression from exogenous reprogramming factors in hiPSC progeny.However,when compared to a tissuederived counterpart,the progeny of both hESCs and hiPSCs maintained expression of a subset of genes normally associated with early mammalian development,regardless of the type of cell generated.While pluripotent genes (OCT4,SOX2,REX1,and NANOG) appeared to be silenced immediately upon differentiation from hPSCs,genes normally unique to early embryos (LIN28A,LIN28B,DPPA4,and others) were not fully silenced in hPSC derivatives.These data and evidence from expression patterns in early human fetal tissue (3-16 weeks of development) suggest that the differentiated progeny of hPSCs are reflective of very early human development (< 6 weeks).These findings provide support for the idea that hPSCs can serve as useful in vitro models of early human development,but also raise important issues for disease modeling and the clinical application of hPSC derivatives.

  12. YAP Induces Human Naive Pluripotency

    Directory of Open Access Journals (Sweden)

    Han Qin

    2016-03-01

    Full Text Available The human naive pluripotent stem cell (PSC state, corresponding to a pre-implantation stage of development, has been difficult to capture and sustain in vitro. We report that the Hippo pathway effector YAP is nuclearly localized in the inner cell mass of human blastocysts. Overexpression of YAP in human embryonic stem cells (ESCs and induced PSCs (iPSCs promotes the generation of naive PSCs. Lysophosphatidic acid (LPA can partially substitute for YAP to generate transgene-free human naive PSCs. YAP- or LPA-induced naive PSCs have a rapid clonal growth rate, a normal karyotype, the ability to form teratomas, transcriptional similarities to human pre-implantation embryos, reduced heterochromatin levels, and other hallmarks of the naive state. YAP/LPA act in part by suppressing differentiation-inducing effects of GSK3 inhibition. CRISPR/Cas9-generated YAP−/− cells have an impaired ability to form colonies in naive but not primed conditions. These results uncover an unexpected role for YAP in the human naive state, with implications for early human embryology.

  13. The Architectural Organization of Human Stem Cell Cycle Regulatory Machinery

    OpenAIRE

    Stein, Gary S.; Stein, Janet L.; van Wijnen, Andre J.; Lian, Jane B.; Montecino, Martin; Medina, Ricardo(Instituto de Matemática e Computação, Universidade Federal de Itajubá, Itajubá, Minas Gerais, Brazil); Kapinas, Kristie; Ghule, Prachi; Grandy, Rodrigo; Zaidi, Sayyed K.; Becker, Klaus A.

    2012-01-01

    Two striking features of human embryonic stem cells that support biological activity are an abbreviated cell cycle and reduced complexity to nuclear organization. The potential implications for rapid proliferation of human embryonic stem cells within the context of sustaining pluripotency, suppressing phenotypic gene expression and linkage to simplicity in the architectural compartmentalization of regulatory machinery in nuclear microenvironments is explored. Characterization of the molecular...

  14. Architectural Slicing

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2013-01-01

    Architectural prototyping is a widely used practice, con- cerned with taking architectural decisions through experiments with light- weight implementations. However, many architectural decisions are only taken when systems are already (partially) implemented. This is prob- lematic in the context of...... architectural prototyping since experiments with full systems are complex and expensive and thus architectural learn- ing is hindered. In this paper, we propose a novel technique for harvest- ing architectural prototypes from existing systems, \\architectural slic- ing", based on dynamic program slicing. Given a...... system and a slicing criterion, architectural slicing produces an architectural prototype that contain the elements in the architecture that are dependent on the ele- ments in the slicing criterion. Furthermore, we present an initial design and implementation of an architectural slicer for Java....

  15. Pluripotent Stem Cells and Gene Therapy

    Science.gov (United States)

    Simara, Pavel; Motl, Jason A.; Kaufman, Dan S.

    2013-01-01

    Human pluripotent stem cells represent an accessible cell source for novel cell-based clinical research and therapies. With the realization of induced pluripotent stem cells (iPSCs), it is possible to produce almost any desired cell type from any patient's cells. Current developments in gene modification methods have opened the possibility for creating genetically corrected human iPSCs for certain genetic diseases that could be used later in autologous transplantation. Promising preclinical studies have demonstrated correction of disease-causing mutations in a number of hematological, neuronal and muscular disorders. This review aims to summarize these recent advances with a focus on iPSC generation techniques, as well as gene modification methods. We will then further discuss some of the main obstacles remaining to be overcome before successful application of human pluripotent stem cell-based therapy arrives in the clinic and what the future of stem cell research may look like. PMID:23353080

  16. Architecture as Ars Combinatoria

    Directory of Open Access Journals (Sweden)

    Francesco Cacciatore

    2015-11-01

    Full Text Available Architecture today, no longer reflects the limits of experimentation and innovation. An extremely low-tech art whose field of possibilities consists of choosing and using that which has already been done in the past. It is because of this that the key skill a designer should have is the ability to recognize the complexity in forms around them: cities have the widest programming opportunities for architecture, in the two-way relationship that is established from the city that takes form in architecture and an architecture that finds its place in the contemporary city. Thus, architecture has its foundation in hospitality, an element that differentiates it significantly from the design.

  17. Architectural Prototyping

    DEFF Research Database (Denmark)

    Bardram, Jakob; Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2004-01-01

    A major part of software architecture design is learning how specific architectural designs balance the concerns of stakeholders. We explore the notion of "architectural prototypes", correspondingly architectural prototyping, as a means of using executable prototypes to investigate stakeholders......' concerns with respect to a system under development. An architectural prototype is primarily a learning and communication vehicle used to explore and experiment with alternative architectural styles, features, and patterns in order to balance different architectural qualities. The use of architectural...... prototypes in the development process is discussed, and we argue that such prototypes can play a role throughout the entire process. The use of architectural prototypes is illustrated by three distinct cases of creating software systems. We argue that architectural prototyping can provide key insights that...

  18. Architectural prototyping

    DEFF Research Database (Denmark)

    Bardram, Jakob Eyvind; Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2004-01-01

    A major part of software architecture design is learning how specific architectural designs balance the concerns of stakeholders. We explore the notion of "architectural prototypes", correspondingly architectural prototyping, as a means of using executable prototypes to investigate stakeholders......' concerns with respect to a system under development. An architectural prototype is primarily a learning and communication vehicle used to explore and experiment with alternative architectural styles, features, and patterns in order to balance different architectural qualities. The use of architectural...... prototypes in the development process is discussed, and we argue that such prototypes can play a role throughout the entire process. The use of architectural prototypes is illustrated by three distinct cases of creating software systems. We argue that architectural prototyping can provide key insights that...

  19. 关于中国石化品牌架构的思考%Reflections on SINOPEC’s BrandArchitecture

    Institute of Scientific and Technical Information of China (English)

    刘晓宇; 童宁

    2014-01-01

    Brand architecture is a structure of brands that specifies the roles of different brands of a company and the logical relationships between the brands, and is designed to take advantage of the collective force of different brands and maximize the brand equity of the company. To improve SINOPEC’s brand architecture in future requires a systematic thinking from four aspects: the driving roles of brand elements, the collective force of brands, brand extension capabilities and integration of acquired businesses.%品牌架构用来描述企业中不同品牌的角色以及品牌之间的逻辑关系,目的是发挥不同品牌的协同效应,最大限度地壮大企业的品牌资产。未来中国石化品牌架构的完善,需要从品牌元素的驱动作用、品牌之间的协同作用、品牌的延伸能力、收购业务的整合四个方面进行系统思考。

  20. A Chemical Probe that Labels Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Nao Hirata

    2014-03-01

    Full Text Available A small-molecule fluorescent probe specific for human pluripotent stem cells would serve as a useful tool for basic cell biology research and stem cell therapy. Screening of fluorescent chemical libraries with human induced pluripotent stem cells (iPSCs and subsequent evaluation of hit molecules identified a fluorescent compound (Kyoto probe 1 [KP-1] that selectively labels human pluripotent stem cells. Our analyses indicated that the selectivity results primarily from a distinct expression pattern of ABC transporters in human pluripotent stem cells and from the transporter selectivity of KP-1. Expression of ABCB1 (MDR1 and ABCG2 (BCRP, both of which cause the efflux of KP-1, is repressed in human pluripotent stem cells. Although KP-1, like other pluripotent markers, is not absolutely specific for pluripotent stem cells, the identified chemical probe may be used in conjunction with other reagents.

  1. Architectural Contestation

    OpenAIRE

    Merle, J.

    2012-01-01

    This dissertation addresses the reductive reading of Georges Bataille's work done within the field of architectural criticism and theory which tends to set aside the fundamental ‘broken’ totality of Bataille's oeuvre and also to narrowly interpret it as a mere critique of architectural form, consequently presenting it either as the negation of all form of architecture or as the critique of 'classical' architectural forms. Against this ‘appropriation’, i.e. this reductive reading and the subse...

  2. Architectural Theatricality

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen; Fisker, Anna Marie; Kirkegaard, Poul Henning

    2013-01-01

    and recovery through the architecture framing eating experiences, this article examines, from a theoretical perspective, two less debated concepts relating to hospitality called food design and architectural theatricality. In architectural theory the nineteenth century German architect Gottfried...... Semper is known for his writings on theatricality, understood as a holistic design approach emphasizing the contextual, cultural, ritual and social meanings rooted in architecture. Relative hereto, the International Food Design Society recently argued, in a similar holistic manner, that the methodology...

  3. VLSI architecture

    Energy Technology Data Exchange (ETDEWEB)

    Randell, B.; Treleaven, P.C.

    1983-01-01

    This book is a collection of course papers which discusses the latest (1982) milestone of electronic building blocks and its effect on computer architecture. Contributions range from selecting a VLSI process technology to Japan's Fifth Generation Computer Architecture. Contents, abridged: VLSI and machine architecture. Graphic design aids: HED and FATFREDDY. On the LUCIFER system. Clocking of VLSI circuits. Decentralised computer architectures for VLSI. Index.

  4. My Reflective Practice as Research.

    Science.gov (United States)

    Pereira, Marcia A.

    1999-01-01

    Using Schon's concepts and definition of reflective practice, this article elaborates a model used to analyze the author's own processes of "reflection-in-action" and "reflection-on-action" in teaching first-year architectural students. Emphasizes the importance of the concept of "role-frame" in informing the whole reflective process. (EV)

  5. Architecture in the network society

    DEFF Research Database (Denmark)

    2004-01-01

    Under the theme Architecture in the Network Society, participants were invited to focus on the dialog and sharing of knowledge between architects and other disciplines and to reflect on, and propose, new methods in the design process, to enhance and improve the impact of information technology...... on architecture. This conference and the past history of eCAADe is an example on establishing a social network for the sharing of knowledge regarding the use of computers in architectural education and research....

  6. Architecture & Environment

    Science.gov (United States)

    Erickson, Mary; Delahunt, Michael

    2010-01-01

    Most art teachers would agree that architecture is an important form of visual art, but they do not always include it in their curriculums. In this article, the authors share core ideas from "Architecture and Environment," a teaching resource that they developed out of a long-term interest in teaching architecture and their fascination with the…

  7. Architectural Theatricality

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen

    This PhD thesis is motived by a personal interest in the theoretical, practical and creative qualities of architecture. But also a wonder and curiosity about the cultural and social relations architecture represents through its occupation with both the sciences and the arts. Inspired by present...... initiatives in Aalborg Hospital to overcome patient undernutrition by refurbishing eating environments, this thesis engages in an investigation of the interior architectural qualities of patient eating environments. The relevance for this holistic perspective, synthesizing health, food and architecture, is...... the current building of a series of Danish ‘super hospitals’ and an increased focus among architectural practices on research-based knowledge produced with the architectural sub-disciplines Healing Architecture and Evidence-Based Design. The problem is that this research does not focus on patient...

  8. Induction of pluripotency by defined factors

    International Nuclear Information System (INIS)

    Somatic cells can be reprogrammed into pluripotent stem cells by introducing a combination of several transcription factors. The induced pluripotent stem (iPS) cells from a patient's somatic cells could be useful source of cells for drug discovery and cell transplantation therapies. However, most human iPS cells are made by viral vectors, such as retrovirus and lentivirus, which integrate the reprogramming factors into host genomes and may increase the risk of tumor formation. Studies of the mechanisms underlying the reprogramming and establishment of non-integration methods contribute evidence to resolve the safety concerns associated with iPS cells. On the other hand, patient-specific iPS cells have already been established and used for recapitulating disease pathology.

  9. Induction of pluripotency by defined factors

    Energy Technology Data Exchange (ETDEWEB)

    Okita, Keisuke, E-mail: okita@cira.kyoto-u.ac.jp [Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507 (Japan); Yamanaka, Shinya [Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507 (Japan); Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507 (Japan); Yamanaka iPS Cell Special Project, Japan Science and Technology Agency, Kawaguchi 332-0012 (Japan); Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158 (United States)

    2010-10-01

    Somatic cells can be reprogrammed into pluripotent stem cells by introducing a combination of several transcription factors. The induced pluripotent stem (iPS) cells from a patient's somatic cells could be useful source of cells for drug discovery and cell transplantation therapies. However, most human iPS cells are made by viral vectors, such as retrovirus and lentivirus, which integrate the reprogramming factors into host genomes and may increase the risk of tumor formation. Studies of the mechanisms underlying the reprogramming and establishment of non-integration methods contribute evidence to resolve the safety concerns associated with iPS cells. On the other hand, patient-specific iPS cells have already been established and used for recapitulating disease pathology.

  10. Vascular Potential of Human Pluripotent Stem Cells

    OpenAIRE

    Iacobas, Ionela; Vats, Archana; Hirschi, Karen K.

    2010-01-01

    Cardiovascular disease is the number one cause of death and disability in the US. Understanding the biological activity of stem and progenitor cells, and their ability to contribute to the repair, regeneration and remodeling of the heart and blood vessels affected by pathologic processes is an essential part of the paradigm in enabling us to achieve a reduction in related deaths. Both human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are promising sources of cells for c...

  11. Epithelial plasticity,stemness and pluripotency

    Institute of Scientific and Technical Information of China (English)

    Oscar H Oca(n)a; M Angela Nieto

    2010-01-01

    @@ Embryonic stem cells derived from the inner cell mass of blastocyst stage embryos(ES cells)are capable of differentiating into any cell type,offering the possibility of their use in cell transplantation therapies.However,the risk of rejection by the immune system and the bioethical issues inherent to the use of embryonic cells prompted the search for a mechanism of obtaining pluripotent cells from adult cells and thus,potentially self tissues.

  12. Induced pluripotent stem cells: advances to applications

    Directory of Open Access Journals (Sweden)

    Timothy J Nelson

    2009-12-01

    Full Text Available Timothy J Nelson1, Almudena Martinez-Fernandez1, Satsuki Yamada1, Yasuhiro Ikeda2, Carmen Perez-Terzic1, Andre Terzic11Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA; 2Department of Molecular Medicine; Mayo Clinic, Rochester, Minnesota, USAAbstract: Induced pluripotent stem cell (iPS technology has enriched the armamentarium of regenerative medicine by introducing autologous pluripotent progenitor pools bioengineered from ordinary somatic tissue. Through nuclear reprogramming, patient-specific iPS cells have been derived and validated. Optimizing iPS-based methodology will ensure robust applications across discovery science, offering opportunities for the development of personalized diagnostics and targeted therapeutics. Here, we highlight the process of nuclear reprogramming of somatic tissues that, when forced to ectopically express stemness factors, are converted into bona fide pluripotent stem cells. Bioengineered stem cells acquire the genuine ability to generate replacement tissues for a wide-spectrum of diseased conditions, and have so far demonstrated therapeutic benefit upon transplantation in model systems of sickle cell anemia, Parkinson’s disease, hemophilia A, and ischemic heart disease. The field of regenerative medicine is therefore primed to adopt and incorporate iPS cell-based advancements as a next generation stem cell platforms.Keywords: iPS, regenerative medicine, individualized medicine, stem cell therapy

  13. Search for naive human pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    Simone Aparecida Siqueira Fonseca; Roberta Montero Costas; Lygia Veiga Pereira

    2015-01-01

    Normal mouse pluripotent stem cells were originallyderived from the inner cell mass (ICM) of blastocystsand shown to be the in vitro equivalent of those preimplantationembryonic cells, and thus were calledembryonic stem cells (ESCs). More than a decade later,pluripotent cells were isolated from the ICM of humanblastocysts. Despite being called human ESCs, thesecells differ significantly from mouse ESCs, includingdifferent morphology and mechanisms of control ofpluripotency, suggesting distinct embryonic originsof ESCs from the two species. Subsequently, mousepluripotent stem cells were established from the ICMderivedepiblast of post-implantation embryos. Thesemouse epiblast stem cells (EpiSCs) are morphologicaland epigenetically more similar to human ESCs. Thisraised the question of whether cells from the humanICM are in a more advanced differentiation stage thantheir murine counterpart, or whether the availableculture conditions were not adequate to maintain thosehuman cells in their in vivo state, leading to a transitioninto EpiSC-like cells in vitro . More recently, novel cultureconditions allowed the conversion of human ESCs intomouse ESC-like cells called naive (or ground state)human ESCs, and the derivation of naive human ESCsfrom blastocysts. Here we will review the characteristicsof each type of pluripotent stem cells, how (andwhether) these relate to different stages of embryonicdevelopment, and discuss the potential implications ofnaive human ESCs in research and therapy.

  14. Rebuilding Pluripotency from Primordial Germ Cells

    Science.gov (United States)

    Leitch, Harry G.; Nichols, Jennifer; Humphreys, Peter; Mulas, Carla; Martello, Graziano; Lee, Caroline; Jones, Ken; Surani, M. Azim; Smith, Austin

    2013-01-01

    Mammalian primordial germ cells (PGCs) are unipotent progenitors of the gametes. Nonetheless, they can give rise directly to pluripotent stem cells in vitro or during teratocarcinogenesis. This conversion is inconsistent, however, and has been difficult to study. Here, we delineate requirements for efficient resetting of pluripotency in culture. We demonstrate that in defined conditions, routinely 20% of PGCs become EG cells. Conversion can occur from the earliest specified PGCs. The entire process can be tracked from single cells. It is driven by leukemia inhibitory factor (LIF) and the downstream transcription factor STAT3. In contrast, LIF signaling is not required during germ cell ontogeny. We surmise that ectopic LIF/STAT3 stimulation reconstructs latent pluripotency and self-renewal. Notably, STAT3 targets are significantly upregulated in germ cell tumors, suggesting that dysregulation of this pathway may underlie teratocarcinogenesis. These findings demonstrate that EG cell formation is a robust experimental system for exploring mechanisms involved in reprogramming and cancer. PMID:24052943

  15. Architectural freedom and industrialised architecture

    DEFF Research Database (Denmark)

    Vestergaard, Inge

    2012-01-01

    Architectural freedom and industrialized architecture. Inge Vestergaard, Associate Professor, Cand. Arch. Aarhus School of Architecture, Denmark Noerreport 20, 8000 Aarhus C Telephone +45 89 36 0000 E-mai l inge.vestergaard@aarch.dk Based on the repetitive architecture from the "building boom" 1960...... to 1973 it is discussed how architects can handle these Danish element and montage buildings through the transformation to upgraded aesthetical, functional and energy efficient architecture. The method used is analysis of cases, parallels to literature studies and producer interviews. This analysis...... compares "best practice" in Denmark and "best practice" in Austria. The modern architects accepted the fact that industrialized architecture told the storey of repetition and monotonous as basic condition. This article aims to explain that architecture can be thought as a complex and diverse design through...

  16. John Hejduk's Pursuit of an Architectural Ethos

    DEFF Research Database (Denmark)

    Søberg, Martin

    2012-01-01

    Reflected, artistic practices and design-based research are drastically expanding fields within architectural academia. However, the interest in uniting theory and practice is not entirely new. Just a few decades ago, before a ‘death of theory’ was proclaimed, questions of architectural epistemol...... – an embracing pursuit of an architectural ethos....

  17. Architecture Sustainability

    OpenAIRE

    Avgeriou, Paris; Stal, Michael; Hilliard, Rich

    2013-01-01

    Software architecture is the foundation of software system development, encompassing a system's architects' and stakeholders' strategic decisions. A special issue of IEEE Software is intended to raise awareness of architecture sustainability issues and increase interest and work in the area. The first Web extra at http://youtu.be/wUGHvocfix0 is an audio interview in which Davide Falessi speaks with guest editors Paris Avgeriou and Rich Hilliard about the importance of architecture sustainabil...

  18. Software architecture

    CERN Document Server

    Vogel, Oliver; Chughtai, Arif

    2011-01-01

    As a software architect you work in a wide-ranging and dynamic environment. You have to understand the needs of your customer, design architectures that satisfy both functional and non-functional requirements, and lead development teams in implementing the architecture. And it is an environment that is constantly changing: trends such as cloud computing, service orientation, and model-driven procedures open up new architectural possibilities. This book will help you to develop a holistic architectural awareness and knowledge base that extends beyond concrete methods, techniques, and technologi

  19. Catalyst Architecture

    DEFF Research Database (Denmark)

    Kiib, Hans; Marling, Gitte; Hansen, Peter Mandal

    2014-01-01

    How can architecture promote the enriching experiences of the tolerant, the democratic, and the learning city - a city worth living in, worth supporting and worth investing in? Catalyst Architecture comprises architectural projects, which, by virtue of their location, context and their combination...... of programs, have a role in mediating positive social and/or cultural development. In this sense, we talk about architecture as a catalyst for: sustainable adaptation of the city’s infrastructure appropriate renovation of dilapidated urban districts strengthening of social cohesiveness in the city...

  20. Reflecting Reflective Practice

    Science.gov (United States)

    Galea, Simone

    2012-01-01

    This paper demystifies reflective practice on teaching by focusing on the idea of reflection itself and how it has been conceived by two philosophers, Plato and Irigaray. It argues that reflective practice has become a standardized method of defining the teacher in teacher education and teacher accreditation systems. It explores how practices of…

  1. The different shades of mammalian pluripotent stem cells

    NARCIS (Netherlands)

    Kuijk, E.W.; Lopes, S.M.; Geijsen, N.; Macklon, N.S.; Roelen, B.A.J.

    2011-01-01

    The different shades of mammalian pluripotent stem cells Abstract BACKGROUND Pluripotent stem cells have been derived from a variety of sources such as from the inner cell mass of preimplantation embryos, from primordial germ cells, from teratocarcinomas and from male germ cells. The recent developm

  2. Citrullination regulates pluripotency and histone H1 binding to chromatin

    DEFF Research Database (Denmark)

    Christophorou, Maria A; Castelo-Branco, Gonçalo; Halley-Stott, Richard P;

    2014-01-01

    response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and...

  3. Reflecting reflection in supervision

    DEFF Research Database (Denmark)

    Lystbæk, Christian Tang

    Reflection has moved from the margins to the mainstream in supervision. Notions of reflection have become well established since the late 1980s. These notions have provided useful framing devices to help conceptualize some important processes in guidance and counseling. However, some applications...... previously associated with reflection and an exploration of alternative conceptions that view reflection within the context of settings which have a more group- and team-based orientation. Drawing on an action research project on health care supervision, the paper questions whether we should reject earlier...... views of reflection, rehabilitate them in order to capture broader connotations or move to new ways of regarding reflection that are more in keeping with not only reflective but also emotive, normative and formative views on supervision. The paper presents a critical perspective on supervision that...

  4. Systemic Architecture

    DEFF Research Database (Denmark)

    Poletto, Marco; Pasquero, Claudia

    2012-01-01

    This is a manual investigating the subject of urban ecology and systemic development from the perspective of architectural design. It sets out to explore two main goals: to discuss the contemporary relevance of a systemic practice to architectural design, and to share a toolbox of informational...... design protocols developed to describe the city as a territory of self-organization. Collecting together nearly a decade of design experiments by the authors and their practice, ecoLogicStudio, the book discusses key disciplinary definitions such as ecologic urbanism, algorithmic architecture, bottom......-up or tactical design, behavioural space and the boundary of the natural and the artificial realms within the city and architecture. A new kind of "real-time world-city" is illustrated in the form of an operational design manual for the assemblage of proto-architectures, the incubation of proto...

  5. Induced Pluripotent Stem Cells Meet Genome Editing.

    Science.gov (United States)

    Hockemeyer, Dirk; Jaenisch, Rudolf

    2016-05-01

    It is extremely rare for a single experiment to be so impactful and timely that it shapes and forecasts the experiments of the next decade. Here, we review how two such experiments-the generation of human induced pluripotent stem cells (iPSCs) and the development of CRISPR/Cas9 technology-have fundamentally reshaped our approach to biomedical research, stem cell biology, and human genetics. We will also highlight the previous knowledge that iPSC and CRISPR/Cas9 technologies were built on as this groundwork demonstrated the need for solutions and the benefits that these technologies provided and set the stage for their success. PMID:27152442

  6. Reflecting on Cherenkov reflections

    OpenAIRE

    Fargion, D.; Gaug, M.; Oliva, P.

    2007-01-01

    Magic Telescope may observe and reveal at horizons lights from air-shower Cherenkov reflections. The ground, the sea, the cloudy sky (below the mountain) may reflect PeVs-EeV UHECR Cherenkov lights observable by MAGIC telescopes. Even rarest UHE neutrino skimming the atmosphere or skimming the Earth may induce upward-horizontal airshowers: a new Neutrino Astronomy. These fluorescence signals or the Cherenkov reflections in upper cloudy sky may flash in correlated BL-Lac or GRB shining at oppo...

  7. GRC3_ALIVE ARCHITECTURE

    OpenAIRE

    Pferdmenges, Petra

    2011-01-01

    The search for the clean and the perfect in our cities is reflected in the spatial exclusion of certain people, especially those on the margin of society. New immigrants, prostitutes and voyageurs are part of those communities often placed in invaluable districts. The concept of the city with a rich diversity of cultures and social backgrounds becomes increasingly a fairy tale, far from reality.As curator of the 4th International Architecture Biennale in Rotterdam (2010) Kees Christiaanse rev...

  8. Mitochondria in human pluripotent stem cell apoptosis.

    Science.gov (United States)

    TeSlaa, Tara; Setoguchi, Kiyoko; Teitell, Michael A

    2016-04-01

    Human pluripotent stem cells (hPSCs) have great potential in regenerative medicine because they can differentiate into any cell type in the body. Genome integrity is vital for human development and for high fidelity passage of genetic information across generations through the germ line. To ensure genome stability, hPSCs maintain a lower rate of mutation than somatic cells and undergo rapid apoptosis in response to DNA damage and additional cell stresses. Furthermore, cellular metabolism and the cell cycle are also differentially regulated between cells in pluripotent and differentiated states and can aid in protecting hPSCs against DNA damage and damaged cell propagation. Despite these safeguards, clinical use of hPSC derivatives could be compromised by tumorigenic potential and possible malignant transformation from failed to differentiate cells. Since hPSCs and mature cells differentially respond to cell stress, it may be possible to specifically target undifferentiated cells for rapid apoptosis in mixed cell populations to enable safer use of hPSC-differentiated cells in patients. PMID:26828436

  9. From pluripotency to distinct cardiomyocyte subtypes.

    Science.gov (United States)

    David, Robert; Franz, Wolfgang-Michael

    2012-06-01

    Differentiated adult cardiomyocytes (CMs) lack significant regenerative potential, which is one reason why degenerative heart diseases are the leading cause of death in the western world. For future cardiac repair, stem cell-based therapeutic strategies may become alternatives to donor heart transplantation. The principle of reprogramming adult terminally differentiated cells (iPSC) had a major impact on stem cell biology. One can now generate autologous pluripotent cells that highly resemble embryonic stem cells (ESC) and that are ethically inoffensive as opposed to human ESC. Yet, due to genetic and epigenetic aberrations arising during the full reprogramming process, it is questionable whether iPSC will enter the clinic in the near future. Therefore, the recent achievement of directly reprogramming fibroblasts into cardiomyocytes via a milder approach, thereby avoiding an initial pluripotent state, may become of great importance. In addition, various clinical scenarios will depend on the availability of specific cardiac cellular subtypes, for which a first step was achieved via our own programming approach to achieve cardiovascular cell subtypes. In this review, we discuss recent progress in the cardiovascular stem cell field addressing the above mentioned aspects. PMID:22689787

  10. Architectural Mealscapes

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen; Fisker, Anna Marie; Kirkegaard, Poul Henning

    2012-01-01

    German architect Gottfried Semper developed a theory on the “four elements of Architecture” tracing the origin of architecture back to the rise of the early human settlement and the creation of fire. With the notion ‘hearth’ as the first motive in architecture and the definition of three enclosing...... motives; mounding, enclosure and roof, Semper linked the cultural and social values of the primordial fireplace with the order and shape of architecture. He claimed that any building ever made was nothing but a variation of the first primitive shelters erected around the fireplace, and that the three...... enclosing motives existed only as defenders of the “sacred flame”. In that way Semper developed the idea that any architectural scenery can be described, analyzed and explained by understanding the contextual, symbolic and social values of how the four basic motives of hearth, mounding, enclosure, and roof...

  11. Framing Architecture

    OpenAIRE

    Shirey, David E.

    2002-01-01

    The following thesis is comprised of a pair of projects focused on the making of architecture through the concept of framing. The work was conducted at the Academia dà ­Architettura in Mendrisio, Switzerland, under the direction of Peter Zumthor, Miguel Kreisler and Myriam Sterling, emphasizing the relationship between ordered structures and contextual propriety. The making of architecture is inherently most pure when approached as the subtraction of unnecessary elements and a distillation ...

  12. Textile Architecture

    OpenAIRE

    Maurin, Bernard; Motro, René

    2013-01-01

    The basic idea for a textile architecture project originates during early meetings between the architect and the engineer. The morphologic richness of such projects is provided by the varying curvatures of shapes, in contradiction with a classical straight line and orthogonal architecture. However the rules of construction are quite different in terms of realisation and of mechanical behaviour: textile membranes are subjected to a pre-stress conferring them their rigidity, and a major objecti...

  13. Fractal Architecture

    OpenAIRE

    Rumież, Agnieszka

    2013-01-01

    Research focuses on the recognition of the disposition of natural environment, which serves as an inspiration for cultural creation as it has always been in the history of architecture. Modern mathematical model of fractal geometry has been used to understand patterns occurring in the surrounding. The comparative analysis has been conducted between the abstract mathematical model and architectural composition in the view of contemporary cognitive paradigms. In conclusion, a hypothesis of a ne...

  14. IAIMS Architecture

    OpenAIRE

    Hripcsak, George

    1997-01-01

    An information system architecture defines the components of a system and the interfaces among the components. A good architecture is essential for creating an Integrated Advanced Information Management System (IAIMS) that works as an integrated whole yet is flexible enough to accommodate many users and roles, multiple applications, changing vendors, evolving user needs, and advancing technology. Modularity and layering promote flexibility by reducing the complexity of...

  15. Nanog, Oct4 and Tet1 interplay in establishing pluripotency.

    Science.gov (United States)

    Olariu, Victor; Lövkvist, Cecilia; Sneppen, Kim

    2016-01-01

    A few central transcription factors inside mouse embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are believed to control the cells' pluripotency. Characterizations of pluripotent state were put forward on both transcription factor and epigenetic levels. Whereas core players have been identified, it is desirable to map out gene regulatory networks which govern the reprogramming of somatic cells as well as the early developmental decisions. Here we propose a multiple level model where the regulatory network of Oct4, Nanog and Tet1 includes positive feedback loops involving DNA-demethylation around the promoters of Oct4 and Tet1. We put forward a mechanistic understanding of the regulatory dynamics which account for i) Oct4 overexpression is sufficient to induce pluripotency in somatic cell types expressing the other Yamanaka reprogramming factors endogenously; ii) Tet1 can replace Oct4 in reprogramming cocktail; iii) Nanog is not necessary for reprogramming however its over-expression leads to enhanced self-renewal; iv) DNA methylation is the key to the regulation of pluripotency genes; v) Lif withdrawal leads to loss of pluripotency. Overall, our paper proposes a novel framework combining transcription regulation with DNA methylation modifications which, takes into account the multi-layer nature of regulatory mechanisms governing pluripotency acquisition through reprogramming. PMID:27146218

  16. Reprogramming of Xist against the pluripotent state in fusion hybrids.

    Science.gov (United States)

    Do, Jeong Tae; Han, Dong Wook; Gentile, Luca; Sobek-Klocke, Ingeborg; Wutz, Anton; Schöler, Hans R

    2009-11-15

    The fusion of somatic cells with pluripotent cells results in the generation of pluripotent hybrid cells. Because the ;memory' of somatic cells seems to be erased during fusion-induced reprogramming, genetic reprogramming is thought to be a largely unidirectional process. Here we show that fusion-induced reprogramming, which brings about the formation of pluripotent hybrids, does not always follow a unidirectional route. Xist is a unique gene in that it is reprogrammed to the state of somatic cells in fusion-induced pluripotent hybrids. In hybrids formed from the cell fusion of embryonal carcinoma cells (ECCs) with male neural stem cells (mNSCs), the Xist gene was found to be reprogrammed to the somatic cell state, whereas the pluripotency-related and tissue-specific marker genes were reprogrammed to the pluripotent cell state. Specifically, Xist is not expressed in hybrids, because the ;memory' of the somatic cell has been retained (i.e. mNSCs do not exhibit Xist expression) and that of the pluripotent cell erased (i.e. inactivation of the partially active Xist gene of ECCs, complete methylation of the Xist region). The latter phenomenon is induced by male, but not by female, NSCs. PMID:19843582

  17. How architecture students gain and apply knowledge of sustainable architecture

    DEFF Research Database (Denmark)

    Donovan, Elizabeth; Holder, Anna

    2016-01-01

    This paper will reflect on understandings of architectural pedagogy and the integration of sustainability into architectural design education. This is framed within an understanding of the construction industry’s role in the production of waste. Despite the complexity of global environmental crises......, architectural educators have the opportunity to do more to address this. We begin with a discussion of contemporary literature and policy concerning education for sustainability in architecture, articulating the particular approaches in development within higher education. This is then compared with critical...... understandings of how architects synthesise different types of knowledge while designing, raising questions about the ‘match’ between educational experiences and subsequent behaviours in practice. Taking an example from Denmark, we outline the approach of Aarhus School of Architecture, where sustainability...

  18. Transverse pumped laser amplifier architecture

    Science.gov (United States)

    Bayramian, Andrew James; Manes, Kenneth; Deri, Robert; Erlandson, Al; Caird, John; Spaeth, Mary

    2013-07-09

    An optical gain architecture includes a pump source and a pump aperture. The architecture also includes a gain region including a gain element operable to amplify light at a laser wavelength. The gain region is characterized by a first side intersecting an optical path, a second side opposing the first side, a third side adjacent the first and second sides, and a fourth side opposing the third side. The architecture further includes a dichroic section disposed between the pump aperture and the first side of the gain region. The dichroic section is characterized by low reflectance at a pump wavelength and high reflectance at the laser wavelength. The architecture additionally includes a first cladding section proximate to the third side of the gain region and a second cladding section proximate to the fourth side of the gain region.

  19. Regulatory insight into the European human pluripotent stem cell registry.

    Science.gov (United States)

    Kurtz, Andreas; Stacey, Glyn; Kidane, Luam; Seriola, Anna; Stachelscheid, Harald; Veiga, Anna

    2014-12-01

    The European pluripotent stem cell registry aims at listing qualified pluripotent stem cell (PSC) lines that are available globally together with relevant information for each cell line. Specific emphasis is being put on documenting ethical procurement of the cells and providing evidence of pluripotency. The report discusses the tasks and challenges for a global PSC registry as an instrument to develop collaboration, to access cells from diverse resources and banks, and to implement standards, and as a means to follow up usage of cells and support adherence to regulatory and scientific standards and transparency for stakeholders. PMID:25457963

  20. Non integrative strategy decreases chromosome instability and improves endogenous pluripotency genes reactivation in porcine induced pluripotent-like stem cells.

    Science.gov (United States)

    Congras, Annabelle; Barasc, Harmonie; Canale-Tabet, Kamila; Plisson-Petit, Florence; Delcros, Chantal; Feraud, Olivier; Oudrhiri, Noufissa; Hadadi, Eva; Griscelli, Franck; Bennaceur-Griscelli, Annelise; Turhan, Ali; Afanassieff, Marielle; Ferchaud, Stéphane; Pinton, Alain; Yerle-Bouissou, Martine; Acloque, Hervé

    2016-01-01

    The pig is an emerging animal model, complementary to rodents for basic research and for biomedical and agronomical purposes. However despite the progress made on mouse and rat models to produce genuine pluripotent cells, it remains impossible to produce porcine pluripotent cell lines with germline transmission. Reprogramming of pig somatic cells using conventional integrative strategies remains also unsatisfactory. In the present study, we compared the outcome of both integrative and non-integrative reprogramming strategies on pluripotency and chromosome stability during pig somatic cell reprogramming. The porcine cell lines produced with integrative strategies express several pluripotency genes but they do not silence the integrated exogenes and present a high genomic instability upon passaging. In contrast, pig induced pluripotent-like stem cells produced with non-integrative reprogramming system (NI-iPSLCs) exhibit a normal karyotype after more than 12 months in culture and reactivate endogenous pluripotency markers. Despite the persistent expression of exogenous OCT4 and MYC, these cells can differentiate into derivatives expressing markers of the three embryonic germ layers and we propose that these NI-iPSLCs can be used as a model to bring new insights into the molecular factors controlling and maintaining pluripotency in the pig and other non-rodent mammalians. PMID:27245508

  1. Architectural Theory: A Construction Site

    Directory of Open Access Journals (Sweden)

    Ákos Moravánszky

    2014-07-01

    Full Text Available Around 1968 we saw the birth of a new architectural theory as the conjunction of architectural history and politically engaged architectural criticism. Not the aesthetics of architecture, but architecture itself in its structural relations with social life became the focus of attention. As a result of this development, it is no longer possible to study architectural history without a critical reflection on the method of the study itself and without a grade of interdisciplinarity. Traditional methods of historiography and iconography have been replaced by new approaches configured by psychoanalysis, deconstruction, cultural studies etc. Appropriation has become the proof of criticality both in architectural theory and in design; however, the understanding of the concepts and methods of other disciplines is basically metaphorical. The problem for a school of architecture lies not in the ‘criticality’ of the kind of architectural theory we described as emerging from the spirit of 1968, but in its discursive nature. The disciplinary specificity of architecture resists a discursive approach, and architectural students frequently question the usefulness of theory which undermines the notion of the ‘project’, without articulating a constructive proposal. Projectivity does not seem to provide an answer; its claim of performativity lacks the program to regain its organising power over contributions from other specialised disciplines and practices. Theory should focus on the terms of our discipline, which are so close to our ‘core beliefs’ regarding architecture that we usually take their meaning for granted. It would be wrong to see this focus of theory as a withdrawal into the realm of language. Indeed, after a period of theory alienating architects and the general public, it could now create a rhetoric to influence our understanding of our environment, which is itself organised on the level of language. The requirement that theory should

  2. Architectural geometry

    KAUST Repository

    Pottmann, Helmut

    2014-11-26

    Around 2005 it became apparent in the geometry processing community that freeform architecture contains many problems of a geometric nature to be solved, and many opportunities for optimization which however require geometric understanding. This area of research, which has been called architectural geometry, meanwhile contains a great wealth of individual contributions which are relevant in various fields. For mathematicians, the relation to discrete differential geometry is significant, in particular the integrable system viewpoint. Besides, new application contexts have become available for quite some old-established concepts. Regarding graphics and geometry processing, architectural geometry yields interesting new questions but also new objects, e.g. replacing meshes by other combinatorial arrangements. Numerical optimization plays a major role but in itself would be powerless without geometric understanding. Summing up, architectural geometry has become a rewarding field of study. We here survey the main directions which have been pursued, we show real projects where geometric considerations have played a role, and we outline open problems which we think are significant for the future development of both theory and practice of architectural geometry.

  3. Long noncoding RNAs in normal and pathological pluripotency

    DEFF Research Database (Denmark)

    Häfner, Sophia J; Talvard, Thomas G; Lund, Anders H

    2016-01-01

    The striking similarities between pluripotent and cancer cells, such as immortality and increased stress resistance, have long been acknowledged. Numerous studies searched for and successfully identified common molecular players and pathways, thus providing an entirely new challenge and potential...

  4. Technical Challenges in the Derivation of Human Pluripotent Cells

    Directory of Open Access Journals (Sweden)

    Parinya Noisa

    2011-01-01

    Full Text Available It has long been discovered that human pluripotent cells could be isolated from the blastocyst state of embryos and called human embryonic stem cells (ESCs. These cells can be adapted and propagated indefinitely in culture in an undifferentiated manner as well as differentiated into cell representing the three major germ layers: endoderm, mesoderm, and ectoderm. However, the derivation of human pluripotent cells from donated embryos is limited and restricted by ethical concerns. Therefore, various approaches have been explored and proved their success. Human pluripotent cells can also be derived experimentally by the nuclear reprogramming of somatic cells. These techniques include somatic cell nuclear transfer (SCNT, cell fusion and overexpression of pluripotent genes. In this paper, we discuss the technical challenges of these approaches for nuclear reprogramming, involving their advantages and limitations. We will also highlight the possible applications of these techniques in the study of stem cell biology.

  5. IAIMS architecture.

    Science.gov (United States)

    Hripcsak, G

    1997-01-01

    An information system architecture defines the components of a system and the interfaces among the components. A good architecture is essential for creating an Integrated Advanced Information Management System (IAIMS) that works as an integrated whole yet is flexible enough to accommodate many users and roles, multiple applications, changing vendors, evolving user needs, and advancing technology. Modularity and layering promote flexibility by reducing the complexity of a system and by restricting the ways in which components may interact. Enterprise-wide mediation promotes integration by providing message routing, support for standards, dictionary-based code translation, a centralized conceptual data schema, business rule implementation, and consistent access to databases. Several IAIMS sites have adopted a client-server architecture, and some have adopted a three-tiered approach, separating user interface functions, application logic, and repositories. PMID:9067884

  6. Architectural Anthropology

    DEFF Research Database (Denmark)

    Stender, Marie

    Architecture and anthropology have always had a common focus on dwelling, housing, urban life and spatial organisation. Current developments in both disciplines make it even more relevant to explore their boundaries and overlaps. Architects are inspired by anthropological insights and methods......, while recent material and spatial turns in anthropology have also brought an increasing interest in design, architecture and the built environment. Understanding the relationship between the social and the physical is at the heart of both disciplines, and they can obviously benefit from further...... collaboration: How can qualitative anthropological approaches contribute to contemporary architecture? And just as importantly: What can anthropologists learn from architects’ understanding of spatial and material surroundings? Recent theoretical developments in anthropology stress the role of materials and...

  7. Architectural Narratives

    DEFF Research Database (Denmark)

    Kiib, Hans

    2010-01-01

    In this essay, I focus on the combination of programs and the architecture of cultural projects that have emerged within the last few years. These projects are characterized as “hybrid cultural projects,” because they intend to combine experience with entertainment, play, and learning. This essay...... identifies new rationales related to this development, and it argues that “cultural planning” has increasingly shifted its focus from a cultural institutional approach to a more market-oriented strategy that integrates art and business. The role of architecture has changed, too. It not only provides a...... functional framework for these concepts, but tries increasingly to endow the main idea of the cultural project with a spatially aesthetic expression - a shift towards “experience architecture.” A great number of these projects typically recycle and reinterpret narratives related to historical buildings and...

  8. Architectural Theatricality

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen

    initiatives in Aalborg Hospital to overcome patient undernutrition by refurbishing eating environments, this thesis engages in an investigation of the interior architectural qualities of patient eating environments. The relevance for this holistic perspective, synthesizing health, food and architecture...... environments and a knowledge gap therefore exists in present hospital designs. Consequently, the purpose of this thesis has been to investigate if any research-based knowledge exist supporting the hypothesis that the interior architectural qualities of eating environments influence patient food intake, health...... such as a literature review, timeline and historical outline to create a “knowledge map”, which in an eclectic manner merges the positive, normative and polemical knowledge rooted in research, objects and writings. The results of these investigations show that sparse researchbased knowledge exist directly taking...

  9. Architectural Anthropology

    DEFF Research Database (Denmark)

    Stender, Marie

    and other spaces that architects are preoccupied with. On the other hand, the distinction between architecture and design is not merely one of scale. Design and architecture represent – at least in Denmark – also quite different disciplinary traditions and methods. Where designers develop prototypes......, architects tend to work with models and plans that are not easily understood by lay people. Further, many architects are themselves sceptical towards notions of user-involvement and collaborative design. They fear that the imagination of citizens and users is restricted to what they are already familiar with...

  10. Reframing Architecture

    DEFF Research Database (Denmark)

    Riis, Søren

    2013-01-01

    I would like to thank Prof. Stephen Read (2011) and Prof. Andrew Benjamin (2011) for both giving inspiring and elaborate comments on my article “Dwelling in-between walls: the architectural surround”. As I will try to demonstrate below, their two different responses not only supplement my article...... focuses on how the absence of an initial distinction might threaten the endeavour of my paper. In my reply to Read and Benjamin, I will discuss their suggestions and arguments, while at the same time hopefully clarifying the postphenomenological approach to architecture....

  11. Multithreading architecture

    CERN Document Server

    Nemirovsky, Mario

    2013-01-01

    Multithreaded architectures now appear across the entire range of computing devices, from the highest-performing general purpose devices to low-end embedded processors. Multithreading enables a processor core to more effectively utilize its computational resources, as a stall in one thread need not cause execution resources to be idle. This enables the computer architect to maximize performance within area constraints, power constraints, or energy constraints. However, the architectural options for the processor designer or architect looking to implement multithreading are quite extensive and

  12. Expression of pluripotency markers in the bovine uterus with adenomyosis

    OpenAIRE

    Łupicka, Martyna; Socha, Barbara; Szczepańska, Agata; Korzekwa, Anna

    2015-01-01

    Background Adenomyosis is a proliferative uterine dysfunction with unknown aetiology. One possible mechanism of its development involves disturbances in stem cell differentiation in uterine tissue. Previously, we identified pluripotent/multipotent cells in the bovine uterus, therefore our present study focused on determining expression of pluripotency markers, NANOG, OCT4 and SOX2, in bovine adenomyotic tissues and cells. Findings Immunolocalisation revealed protein expression of NANOG, OCT4 ...

  13. Human pluripotent stem cells: an emerging model in developmental biology

    OpenAIRE

    Zhu, Zengrong; Huangfu, Danwei

    2013-01-01

    Developmental biology has long benefited from studies of classic model organisms. Recently, human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, have emerged as a new model system that offers unique advantages for developmental studies. Here, we discuss how studies of hPSCs can complement classic approaches using model organisms, and how hPSCs can be used to recapitulate aspects of human embryonic development ‘in a dish’. We also...

  14. A simple tool to improve pluripotent stem cell differentiation

    OpenAIRE

    Chetty, Sundari; Pagliuca, Felicia Walton; Honore, Christian; Kweudjeu, Anastasie; Rezania, Alireza; Melton, Douglas A.

    2013-01-01

    We develop a method to overcome previously documented restrictions on the differentiation propensities of pluripotent stem cells. Culturing pluripotent stem cells in dimethylsulfoxide (DMSO) activates the retinoblastoma protein, increases the proportion of cells in the early G1 phase of the cell cycle, and subsequently improves their competency for directed differentiation into multiple lineages in more than 25 stem cell lines. DMSO treatment also promotes terminal differentiation into functi...

  15. Adult hematopoietic progenitors are pluripotent in chimeric mice

    OpenAIRE

    Pessac, Bernard; K. Nimmagadda, Vamshi; Makar, Tapas; S. Fishman, Paul; T. Bever Jr., Christopher; Trisler, David

    2012-01-01

    18 pages, 7 figures. Embryonic stem cells (ESCs) and adult somatic cells, induced to pluripotency (iPSCs) by genetic manipulation, display high self-­‐renewal potential and the capacity to differentiate into multiple cell lineages. We asked whether there are in adult mammals natural stem cells that are pluripotent. We previously reported that normal adult mammalian bone marrow contains a sub-­‐population of CD34+ cells, that naturally expresses genes characteristic of ESCs and those requir...

  16. Cell Pluripotency Levels Associated with Imprinted Genes in Human

    Directory of Open Access Journals (Sweden)

    Liyun Yuan

    2015-01-01

    Full Text Available Pluripotent stem cells are exhibited similarly in the morphology, gene expression, growth properties, and epigenetic modification with embryonic stem cells (ESCs. However, it is still controversial that the pluripotency of induced pluripotent stem cell (iPSC is much inferior to ESC, and the differentiation capacity of iPSC and ESC can also be separated by transcriptome and epigenetics. miRNAs, which act in posttranscriptional regulation of gene expression and are involved in many basic cellular processes, may reveal the answer. In this paper, we focused on identifying the hidden relationship between miRNAs and imprinted genes in cell pluripotency. Total miRNA expression patterns in iPSC and ES cells were comprehensively analysed and linked with human imprinted genes, which show a global picture of their potential function in pluripotent level. A new CPA4-KLF14 region which locates in chromosomal homologous segments (CHSs within mammals and include both imprinted genes and significantly expressed miRNAs was first identified. Molecular network analysis showed genes interacted with imprinted genes closely and enriched in modules such as cancer, cell death and survival, and tumor morphology. This imprinted region may provide a new look for those who are interested in cell pluripotency of hiPSCs and hESCs.

  17. Cell Pluripotency Levels Associated with Imprinted Genes in Human.

    Science.gov (United States)

    Yuan, Liyun; Tang, Xiaoyan; Zhang, Binyan; Ding, Guohui

    2015-01-01

    Pluripotent stem cells are exhibited similarly in the morphology, gene expression, growth properties, and epigenetic modification with embryonic stem cells (ESCs). However, it is still controversial that the pluripotency of induced pluripotent stem cell (iPSC) is much inferior to ESC, and the differentiation capacity of iPSC and ESC can also be separated by transcriptome and epigenetics. miRNAs, which act in posttranscriptional regulation of gene expression and are involved in many basic cellular processes, may reveal the answer. In this paper, we focused on identifying the hidden relationship between miRNAs and imprinted genes in cell pluripotency. Total miRNA expression patterns in iPSC and ES cells were comprehensively analysed and linked with human imprinted genes, which show a global picture of their potential function in pluripotent level. A new CPA4-KLF14 region which locates in chromosomal homologous segments (CHSs) within mammals and include both imprinted genes and significantly expressed miRNAs was first identified. Molecular network analysis showed genes interacted with imprinted genes closely and enriched in modules such as cancer, cell death and survival, and tumor morphology. This imprinted region may provide a new look for those who are interested in cell pluripotency of hiPSCs and hESCs. PMID:26504487

  18. From green architecture to architectural green

    DEFF Research Database (Denmark)

    Earon, Ofri

    2011-01-01

    The paper investigates the topic of green architecture from an architectural point of view and not an energy point of view. The purpose of the paper is to establish a debate about the architectural language and spatial characteristics of green architecture. In this light, green becomes an adjective...... that describes the architectural exclusivity of this particular architecture genre. The adjective green expresses architectural qualities differentiating green architecture from none-green architecture. Currently, adding trees and vegetation to the building’s facade is the main architectural characteristics...... of green architecture. The paper argues that this greenification of facades is insufficient. The green is only a skin cladding the exterior envelope without having a spatial significance. Through the paper it is proposed to flip the order of words from green architecture to architectural green...

  19. Religious Architecture

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The main religions of ancient China were Buddhism,Taoism and Islam, of which Buddhism was the most widespread. As a result, Buddhist temples and towers are found all over China, and have become important components of the country's ancient architecture.

  20. Reflective Teaching

    Science.gov (United States)

    Farrell, Thomas S. C.

    2013-01-01

    Thomas Farrell's "Reflective Teaching" outlines four principles that take teachers from just doing reflection to making it a way of being. Using the four principles, Reflective Practice Is Evidence Based, Reflective Practice Involves Dialogue, Reflective Practice Links Beliefs and Practices, and Reflective Practice Is a Way of Life,…

  1. Performative Urban Architecture

    DEFF Research Database (Denmark)

    Thomsen, Bo Stjerne; Jensen, Ole B.

    The paper explores how performative urban architecture can enhance community-making and public domain using socio-technical systems and digital technologies to constitute an urban reality. Digital medias developed for the web are now increasingly occupying the urban realm as a tool for navigating...... discusses the perspectives of using interactive technologies for performative objects, which are able to register the impulses of urban activity and reproduce the contexts of the city. In this way the performative environment is established as an event setting providing an embodied experience as a ‘quasi......-object' that can couple relationships between architecture, humans and society. These performative relationships between digital and physical environments are seen as illustrative of the social production of space by performance and the creative production of identity. The paper reflects on the perspectives of...

  2. Temporal repression of endogenous pluripotency genes during reprogramming of porcine induced pluripotent stem cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane; Christensen, Marianne; Rasmussen, Mikkel Aabech;

    2012-01-01

    transgenes on the expression of the porcine endogenous pluripotency machinery. Endogenous and exogenous gene expression of OCT4, NANOG, SOX2, KLF4, and cMYC was determined at passages 5, 10, 15, and 20, both in cells cultured at 1¿µg/mL doxycycline or 4¿µg/mL doxycycline. Our results revealed that endogenous....... Despite the ability for some endogenous genes to be expressed in these lines, the piPSC-like cells still cannot be maintained without doxycycline, indicating that the culture system of piPSCs may not be optimal or that the reprogramming factor combination used may not currently be optimal for maintaining...

  3. The molecular mechanism of embryonic stem cell pluripotency maintenance

    Institute of Scientific and Technical Information of China (English)

    WANG Qingzhong; LIU Yixun; HAN Chunsheng

    2005-01-01

    In vitro cultured embryonic stem (ES) cells are derived from the inner cell mass (ICM) of pre-implantation embryos, and are capable of giving rise to all cell and tissue types of the three germ layers upon being injected back into blastocysts. These cells are therefore said to possess pluripotency that can be maintained infinitely in culture under optimal conditions. Such pluripotency maintenance is believed to be due to the symmetrical cleavage of the cells in an undifferentiated state. The pluripotency of ES cells is the basis for their various practical and potential applications. ES cells can be used as donor cells to generate knockout or transgenic animals, as in vitro models of mammalian development, and as cell resources for cell therapy in regenerative medicine. The further success in these applications, particularly in the last two, is dependent on the establishment of a culture system with components in the medium clearly defined and the subsequent procedures for controlled differentiation of the cells into specific lineages. In turn, elucidating the molecular mechanism for pluripotency maintenance of ES cells is the prerequisite. This paper summarizes the recent progresses in this area, focusing mainly on the LIF/STAT3, BMPs/Smads, canonical Wnt, TGFβ/activin/nodal, PI3K and FGF signaling pathways and the genes such as oct4, nanog that are crucial in ES cell pluripotency maintenance. The regulatory systems of pluripotency maintenance in both mouse and human ES cells are also discussed. We believe that the cross-talkings between these signaling pathways, as well as the regulatory system underlying pluripotency maintenance will be the main focus in the area of ES cell researches in the future.

  4. Kosmos = architecture

    Directory of Open Access Journals (Sweden)

    Tine Kurent

    2015-10-01

    Full Text Available The old Greek word "kosmos" means not only "cosmos", but also "the beautiful order", "the way of building", "building", "scenography", "mankind", and, in the time of the New Testament, also "pagans". The word "arhitekton", meaning first the "master of theatrical scenography", acquired the meaning of "builder", when the words "kosmos" and ~kosmetes" became pejorative. The fear that architecture was not considered one of the arts before Renaissance, since none of the Muses supervised the art of building, results from the misunderstanding of the word "kosmos". Urania was the Goddes of the activity implied in the verb "kosmein", meaning "to put in the beautiful order" - everything, from the universe to the man-made space, i. e. the architecture.

  5. MUF architecture /art London

    DEFF Research Database (Denmark)

    Svenningsen Kajita, Heidi

    2009-01-01

    Om MUF architecture samt interview med Liza Fior og Katherine Clarke, partnere i muf architecture/art......Om MUF architecture samt interview med Liza Fior og Katherine Clarke, partnere i muf architecture/art...

  6. THE DYNAMICS OF THE FORM OF NUSANTARA MOSQUE: ARCHITECTURAL HOMOGENEITY VIS A VIS ARCHITECTURAL HYBRIDITY

    Directory of Open Access Journals (Sweden)

    Pudji Pratitis Wismantara

    2012-09-01

    Full Text Available There are two points of departure in the design of mosque architecture in Nusantara, namely architectural homogeneity and architectural hybridity. Each provides the legitimacy of the architecture of identity formation. This paper seeks to explore the comparative, the concept of homogeneity and hybridity architecture, with a critical theory approach. The  results of this search is, the concept of architectural homogeneity establishing assumption that certain architectural forms are supposed to represent "universal identity and modernity" of Muslim architecture. Meanwhile, the concept of architectural hybridity to show enrichment architecture identity because of the attempt to combine aspects of the universality of Islam with locality of Nusantara. Both these aspects can be positioned as the two subjects of mutual dialogue in a parallel position. As architecture strategy, the concept of hybridity reflects the effort or ijtihad in interpreting local and universal contextuality in the contemporary conditions that are constantly evolving and open.Keywords: Nusantara mosque, hybridity of architecture, homogeneity of architecture, architecture strategy

  7. Genome Editing in Human Pluripotent Stem Cells.

    Science.gov (United States)

    Smith, Cory; Ye, Zhaohui; Cheng, Linzhao

    2016-01-01

    Pluripotent stem cells (PSCs), defined by their capacity for self-renewal and differentiation into all cell types, are an integral tool for basic biological research and disease modeling. However, full use of PSCs for research and regenerative medicine requires the ability to precisely edit their DNA to correct disease-causing mutations and for functional analysis of genetic variations. Recent advances in DNA editing of human stem cells (including PSCs) have benefited from the use of designer nucleases capable of making double-strand breaks (DSBs) at specific sequences that stimulate endogenous DNA repair. The clustered, regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has become the preferred designer nuclease for genome editing in human PSCs and other cell types. Here we describe the principles for designing a single guide RNA to uniquely target a gene of interest and describe strategies for disrupting, inserting, or replacing a specific DNA sequence in human PSCs. The improvements in efficiency and ease provided by these techniques allow individuals to precisely engineer PSCs in a way previously limited to large institutes and core facilities. PMID:27037079

  8. Neural repair with pluripotent stem cells.

    Science.gov (United States)

    Döbrössy, Máté; Pruszak, Jan

    2013-01-01

    The nervous system is characterized by its complex network of highly specialized cells that enable us to perceive stimuli from the outside world and react accordingly. The computational integration enabled by these networks remains to be elucidated, but appropriate sensory input, processing, and motor control are certainly essential for survival. Consequently, loss of nervous tissue due to injury or disease represents a considerable biomedical challenge. Stem cell research offers the promise to provide cells for nervous system repair to replace lost and damaged neural tissue and alleviate disease. We provide a protocol-based chapter on fundamental principles and procedures of pluripotent stem cell (PSC) differentiation and neural transplantation. Rather than detailed methodological step-by-step descriptions of these procedures, we provide an overview and highlight the most critical aspects and key steps of PSC neural induction, subtype specification in different in vitro systems, as well as neural cell transplantation to the central nervous system. We conclude with a summary of suitable readout methods including in vitro phenotypic analysis, histology, and functional analysis in vivo. PMID:24029933

  9. Chaotic expression dynamics implies pluripotency: when theory and experiment meet

    Directory of Open Access Journals (Sweden)

    Furusawa Chikara

    2009-05-01

    Full Text Available Abstract Background During normal development, cells undergo a unidirectional course of differentiation that progressively decreases the number of cell types they can potentially become. Pluripotent stem cells can differentiate into several types of cells, but terminally differentiated cells cannot differentiate any further. A fundamental problem in stem cell biology is the characterization of the difference in cellular states, e.g., gene expression profiles, between pluripotent stem cells and terminally differentiated cells. Presentation of the hypothesis To address the problem, we developed a dynamical systems model of cells with intracellular protein expression dynamics and interactions with each other. According to extensive simulations, cells with irregular (chaotic oscillations in gene expression dynamics have the potential to differentiate into other cell types. During development, such complex oscillations are lost successively, leading to a loss of pluripotency. These simulation results, together with recent single-cell-level measurements in stem cells, led us to the following hypothesis regarding pluripotency: Chaotic oscillation in the expression of some genes leads to cell pluripotency and affords cellular state heterogeneity, which is supported by itinerancy over quasi-stable states. Differentiation stabilizes these states, leading to a loss of pluripotency. Testing the hypothesis To test the hypothesis, it is crucial to measure the time course of gene expression levels at the single-cell level by fluorescence microscopy and fluorescence-activated cell sorting (FACS analysis. By analyzing the time series of single-cell-level expression data, one can distinguish whether the variation in protein expression level over time is due only to stochasticity in expression dynamics or originates from the chaotic dynamics inherent to cells, as our hypothesis predicts. By further analyzing the expression in differentiated cell types, one can

  10. Induced pluripotent stem cells: Mechanisms, achievementsand perspectives in farm animals

    Institute of Scientific and Technical Information of China (English)

    Dharmendra Kumar; Thirumala R Talluri; Taruna Anand; Wilfried A Kues

    2015-01-01

    Pluripotent stem cells are unspecialized cells withunlimited self-renewal, and they can be triggered todifferentiate into desired specialized cell types. Thesefeatures provide the basis for an unlimited cell sourcefor innovative cell therapies. Pluripotent cells also allowto study developmental pathways, and to employ themor their differentiated cell derivatives in pharmaceuticaltesting and biotechnological applications. Via blastocystcomplementation, pluripotent cells are a favoured toolfor the generation of genetically modified mice. Therecently established technology to generate an inducedpluripotency status by ectopic co-expression of thetranscription factors Oct4, Sox2, Klf4 and c-Myc allowsto extending these applications to farm animal species,for which the derivation of genuine embryonic stemcells was not successful so far. Most induced pluripotentstem (iPS) cells are generated by retroviral or lentiviraltransduction of reprogramming factors. Multiple viralintegrations into the genome may cause insertionalmutagenesis and may increase the risk of tumourformation. Non-integration methods have been reportedto overcome the safety concerns associated withretro and lentiviral-derived iPS cells, such as transientexpression of the reprogramming factors using episomalplasmids, and direct delivery of reprogrammingmRNAs or proteins. In this review, we focus on themechanisms of cellular reprogramming and currentmethods used to induce pluripotency. We also highlightproblems associated with the generation of iPS cells. Anincreased understanding of the fundamental mechanismsunderlying pluripotency and refining the methodology ofiPS cell generation will have a profound impact on futuredevelopment and application in regenerative medicineand reproductive biotechnology of farm animals.

  11. Reflection, Reflective Practice and Embodied Reflective Practice

    OpenAIRE

    Leigh, Jennifer S; Bailey, Richard

    2013-01-01

    Although widely employed in professional practice of all kinds, ‘reflection’ and ‘reflective practice’ can be considered ‘success words’. That is, they elicit positive and supportive responses and yet the concepts are vague, ill-defined, contradictory and reflective skills can be hard to teach. Using examples from education and somatic movement therapy, we argue that a purely analytical approach to reflective practice that involves reflecting on thoughts alone is likely to lead into a negativ...

  12. Haptic architecture becomes architectural hap

    OpenAIRE

    Herssens, Jasmien; Heylighen, Ann

    2007-01-01

    Universal Design is a recent design paradigm which aims at handicap elimination in the physical environment and strives for a more humanized architecture. After pointing out the value of Universal Design, the paper advances human centred design as a possible methodology to make this paradigm operational. Key to this methodology is the explicit attention for cognitive human factors in experiencing space and—the focus of this paper—for the role played by the sense of tou...

  13. Reflection Coefficients.

    Science.gov (United States)

    Greenslade, Thomas B., Jr.

    1994-01-01

    Discusses and provides an example of reflectivity approximation to determine whether reflection will occur. Provides a method to show thin-film interference on a projection screen. Also applies the reflectivity concepts to electromagnetic wave systems. (MVL)

  14. Generation and Characterization of Leukemia Inhibitory Factor-Dependent Equine Induced Pluripotent Stem Cells from Adult Dermal Fibroblasts

    Science.gov (United States)

    Ovchinnikov, Dmitry A.; Sun, Jane; Fortuna, Patrick R.J.; Wolvetang, Ernst J.

    2014-01-01

    In this study we have reprogrammed dermal fibroblasts from an adult female horse into equine induced pluripotent stem cells (equiPSCs). These equiPSCs are dependent only on leukemia inhibitory factor (LIF), placing them in striking contrast to previously derived equiPSCs that have been shown to be co-dependent on both LIF and basic fibroblast growth factor (bFGF). These equiPSCs have a normal karyotype and have been maintained beyond 60 passages. They possess alkaline phosphatase activity and express eqNANOG, eqOCT4, and eqTERT mRNA. Immunocytochemistry confirmed that they produce NANOG, REX1, SSEA4, TRA1-60, and TRA1-81. While our equiPSCs are LIF dependent, bFGF co-stimulates their proliferation via the PI3K/AKT pathway. EquiPSCs lack expression of eqXIST and immunostaining for H3K27me3, suggesting that during reprogramming the inactive X chromosome has likely been reactivated to generate cells that have two active X chromosomes. EquiPSCs form embryoid bodies and in vitro teratomas that contain derivatives of all three germ layers. These LIF-dependent equiPSCs likely reflect a more naive state of pluripotency than equiPSCs that are co-dependent on both LIF and bFGF and so provide a novel resource for understanding pluripotency in the horse. PMID:24555755

  15. Textile Architecture

    DEFF Research Database (Denmark)

    Heimdal, Elisabeth Jacobsen

    2010-01-01

    Textiles can be used as building skins, adding new aesthetic and functional qualities to architecture. Just like we as humans can put on a coat, buildings can also get dressed. Depending on our mood, or on the weather, we can change coat, and so can the building. But the idea of using textiles...... to create human habitation is not new. As Diether S. Hope phrases it, referring to tents: The history of development of humanity would be barely conceivable without free spanning textile membrane structures....

  16. Architecture of the human XPC DNA repair and stem cell coactivator complex.

    Science.gov (United States)

    Zhang, Elisa T; He, Yuan; Grob, Patricia; Fong, Yick W; Nogales, Eva; Tjian, Robert

    2015-12-01

    The Xeroderma pigmentosum complementation group C (XPC) complex is a versatile factor involved in both nucleotide excision repair and transcriptional coactivation as a critical component of the NANOG, OCT4, and SOX2 pluripotency gene regulatory network. Here we present the structure of the human holo-XPC complex determined by single-particle electron microscopy to reveal a flexible, ear-shaped structure that undergoes localized loss of order upon DNA binding. We also determined the structure of the complete yeast homolog Rad4 holo-complex to find a similar overall architecture to the human complex, consistent with their shared DNA repair functions. Localized differences between these structures reflect an intriguing phylogenetic divergence in transcriptional capabilities that we present here. Having positioned the constituent subunits by tagging and deletion, we propose a model of key interaction interfaces that reveals the structural basis for this difference in functional conservation. Together, our findings establish a framework for understanding the structure-function relationships of the XPC complex in the interplay between transcription and DNA repair. PMID:26627236

  17. Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Hall, Vanessa J.

    2016-01-01

    Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease......, frontotemporal dementia and Parkinson’s disease using pluripotent stem cells is described, along with the advent of gene-editing, which has been the complimentary tool for the field. Current methods used to model these diseases are predominantly dependent on 2D cell culture methods. Outcomes reveal that only...... includes studying more complex 3D cell cultures, as well as accelerating aging of the neurons, may help to yield stronger phenotypes in the cultured cells. Thus, the use and application of pluripotent stem cells for modelling disease have already shown to be a powerful approach for discovering more about...

  18. Teratoma: from spontaneous tumors to the pluripotency/malignancy assay.

    Science.gov (United States)

    Bulic-Jakus, Floriana; Katusic Bojanac, Ana; Juric-Lekic, Gordana; Vlahovic, Maja; Sincic, Nino

    2016-01-01

    A teratoma is a benign tumor containing a mixture of differentiated tissues and organotypic derivatives of the three germ layers, while a teratocarcinoma also contains embryonal carcinoma cells (EC cells). Experimental teratomas and teratocarcinomas have been derived from early mammalian embryos transplanted into the adult animal (ectopic sites). In the rat, the pluripotency of the transplanted epiblast was demonstrated and a quantifiable restriction of developmental potential persisted after subsequent transplantation of chemically defined cultivated postimplantation embryos. The rat is nonpermissive for teratocarcinoma development and rat pluripotent cell lines have been established only recently. Transplantation of mouse embryos, epiblast, or embryonic stem cells (mESCs) gave rise to teratocarcinomas. The pluripotency of reprogrammed human cells has been tested by a 'gold standard' trilaminar teratoma assay in immunocompromised mice in vivo. Human pluripotent stem cells proposed for use in regenerative medicine such as human embryonic stem cell (hESC), human nuclear-transfer/therapeutic cloning embryonic stem cell (NT-ESC), or human induced pluripotent stem cell (hiPSC) lines, once differentiated in vitro to the desired cell type, should be again tested in a long-term animal teratoma assay to exclude their malignancy. Such an approach led to a recently implemented human therapy with retinal pigmented epithelium. For greater biosafety, the teratoma assay should be standardized and complemented by assessments of mutations/epimutations, RNA/protein expression, and possible immunogenicity of autologous pluripotent cells. Furthermore, the standardized teratoma assay should be directed more to the assessment of EC/malignant cell features than of differentiated tissues, especially after a unique case of human therapy with neural stem cells was found to lead to malignancy. For further resources related to this article, please visit the WIREs website. PMID:26698368

  19. Identification of Pluripotency Genes in the Fish Medaka

    Directory of Open Access Journals (Sweden)

    Danke Wang, Dwarakanath Manali, Tiansu Wang, Narayani Bhat, Ni Hong, Zhendong Li, Li Wang, Yan Yan, Rong Liu, Yunhan Hong

    2011-01-01

    Full Text Available Stem cell cultures can be derived directly from early developing embryos and indirectly from differentiated cells by forced expression of pluripotency transcription factors. Pluripotency genes are routinely used to characterize mammalian stem cell cultures at the molecular level. However, such genes have remained unknown in lower vertebrates. In this regard, the laboratory fish medaka is uniquely suited because it has embryonic stem (ES cells and genome sequence data. We identified seven medaka pluripotency genes by homology search and expression in vivo and in vitro. By RT-PCR analysis, the seven genes fall into three groups of expression pattern. Group I includes nanog and oct4 showing gonad-specific expression; Group II contains sall4 and zfp281 displaying gonad-preferential expression; Group III has klf4, ronin and tcf3 exhibiting expression also in several somatic tissues apart from the gonads. The transcripts of the seven genes are maternally supplied and persist at a high level during early embryogenesis. We made use of early embryos and adult gonads to examine expression in stem cells and differentiated derivatives by in situ hybridization. Strikingly, nanog and oct4 are highly expressed in pluripotent blastomeres of 16-cell embryos. In the adult testis, nanog expression was specific to spermatogonia, the germ stem cells, whereas tcf3 expression occurred in spermatogonia and differentiated cells. Most importantly, all the seven genes are pluripotency markers in vitro, because they have high expression in undifferentiated ES cells but dramatic down-regulation upon differentiation. Therefore, these genes have conserved their pluripotency-specific expression in vitro from mammals to lower vertebrates.

  20. Canine pluripotent stem cells: Are they ready for clinical applications?

    Directory of Open Access Journals (Sweden)

    Dean Harvey Betts

    2015-10-01

    Full Text Available The derivation of canine embryonic stem cells and generation of canine induced pluripotent stem cells are significant achievements that have unlocked the potential for developing novel cell-based disease models, drug discovery platforms and transplantation therapies in the dog. A progression from concept to cure in this clinically relevant companion animal will not only help our canine patients but also help advance human regenerative medicine. Nevertheless, many issues remain to be resolved before pluripotent cells can be used clinically in a safe and reproducible manner.

  1. 夏热冬冷地区建筑反射隔热涂料应用的技术要点%The Technical Points of Application for the Architectural Reflective Thermal Insulation Coatings in Hot Summer and Cold Winter Zone

    Institute of Scientific and Technical Information of China (English)

    薛黎明

    2011-01-01

    介绍了建筑反射隔热涂料在工程应用中的主要技术问题和实施要点,包括建筑反射隔热涂料的应用特点、应用方式、涂层构造和技术指标要求,以及设计要点和施工技术等。其主要应用方式是建筑反射隔热涂料一无机保温砂浆外墙外保温体系,以及建筑反射隔热涂料一保温腻子层体系两种方式。设计中,首先应满足建筑节能规定的建筑物传热阻值,并将涂料等效热阻考虑到设计中;涂膜最小厚度和变形缝的设置等也是设计中应当考虑的问题。%The main technical insulation coatings in the enginee problem and implementation points of the architectural reflective thermal ring application were introduced. These contents were included: the application characteristics, the application way, the coating structure, the technical index requests, and the main pionts for design and the construction technology etc. The main application way were the architectural reflective thermal insulating coatings-inorganic thermal insulation mortar system, and the architectural reflective thermal insulating coatings-thermal insulation p energy-saving design was satisfie system. d, and In the the eq thickness of the film and setting deformation design, the thermal resistance of the building regulated in build uivalent thermal resistance of coatings was calculated. The least int were also considered in the design.

  2. Mapping Human Pluripotent-to-Cardiomyocyte Differentiation: Methylomes, Transcriptomes, and Exon DNA Methylation “Memories”

    Directory of Open Access Journals (Sweden)

    Joshua D. Tompkins

    2016-02-01

    Full Text Available The directed differentiation of human cardiomyocytes (CMs from pluripotent cells provides an invaluable model for understanding mechanisms of cell fate determination and offers considerable promise in cardiac regenerative medicine. Here, we utilize a human embryonic stem cell suspension bank, produced according to a good manufacturing practice, to generate CMs using a fully defined and small molecule-based differentiation strategy. Primitive and cardiac mesoderm purification was used to remove non-committing and multi-lineage populations and this significantly aided the identification of key transcription factors, lncRNAs, and essential signaling pathways that define cardiomyogenesis. Global methylation profiles reflect CM development and we report on CM exon DNA methylation “memories” persisting beyond transcription repression and marking the expression history of numerous developmentally regulated genes, especially transcription factors.

  3. Mapping Human Pluripotent-to-Cardiomyocyte Differentiation: Methylomes, Transcriptomes, and Exon DNA Methylation "Memories".

    Science.gov (United States)

    Tompkins, Joshua D; Jung, Marc; Chen, Chang-Yi; Lin, Ziguang; Ye, Jingjing; Godatha, Swetha; Lizhar, Elizabeth; Wu, Xiwei; Hsu, David; Couture, Larry A; Riggs, Arthur D

    2016-02-01

    The directed differentiation of human cardiomyocytes (CMs) from pluripotent cells provides an invaluable model for understanding mechanisms of cell fate determination and offers considerable promise in cardiac regenerative medicine. Here, we utilize a human embryonic stem cell suspension bank, produced according to a good manufacturing practice, to generate CMs using a fully defined and small molecule-based differentiation strategy. Primitive and cardiac mesoderm purification was used to remove non-committing and multi-lineage populations and this significantly aided the identification of key transcription factors, lncRNAs, and essential signaling pathways that define cardiomyogenesis. Global methylation profiles reflect CM development and we report on CM exon DNA methylation "memories" persisting beyond transcription repression and marking the expression history of numerous developmentally regulated genes, especially transcription factors. PMID:26981572

  4. Pathways in pluripotency and differentiation of embryonic cells

    NARCIS (Netherlands)

    du Puy, L.

    2010-01-01

    Pluripotency - the potential to differentiate into derivatives of the three embryonic germ layers endoderm, ectoderm and mesoderm - is the main characteristic of embryonic stem (ES) cells. ES cells are derived from the inner cell mass (ICM) of a pre-implantation blastocyst and can self-renew indefin

  5. Differentiation of Induced Pluripotent Stem Cells Into Functional Oligodendrocytes

    NARCIS (Netherlands)

    Czepiel, Marcin; Balasubramaniyan, Veerakumar; Schaafsma, Wandert; Stancic, Mirjana; Mikkers, Harald; Huisman, Christian; Boddeke, Erik; Copray, Sjef

    2011-01-01

    The technology to generate autologous pluripotent stem cells (iPS cells) from almost any somatic cell type has brought various cell replacement therapies within clinical research. Besides the challenge to optimize iPS protocols to appropriate safety and GMP levels, procedures need to be developed to

  6. The Secret Lives of Pluripotent Cells: There and Back Again

    Directory of Open Access Journals (Sweden)

    Paolo Cinelli

    2010-03-01

    Full Text Available Embryonic stem cells (ESCs and induced pluripotent stem cells (IPSCs hold great promise for the therapeutic treatment of human diseases, but their functional similarity, their stability and especially the mechanism underlying their derivation are not yet clearly explained. [...

  7. Germ cells and the origins of mammalian pluripotent cells

    NARCIS (Netherlands)

    Kuijk, E.W.

    2009-01-01

    Mammalian embryonic stem (ES) cells originate from preimplantation embryos and can be propagated indefinitely without loss of pluripotency; i.e. the potential to develop into any embryonic cell type. ES cells have been described for mouse, rhesus monkey, and human. There is considerable interest in

  8. Oct4: the final frontier, differentiation defining pluripotency

    DEFF Research Database (Denmark)

    Livigni, Alessandra; Brickman, Joshua M

    2013-01-01

    The transcription factor OCT4 is a cornerstone of pluripotency, and yet OCT4 has also been associated with differentiation in a number of contexts. Reporting in this issue of Developmental Cell, Frum et al. (2013) show that OCT4's major early activity in the blastocyst is to support primitive...

  9. Uncovering the true identity of naive pluripotent stem cells

    NARCIS (Netherlands)

    Welling, M.; Geijsen, N.

    2013-01-01

    Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass (ICM) of blastocyst embryos. Although first characterized over 30 years ago, the ontology of these cells remains elusive. Identifying the in vivo counterpart of murine ESCs will be essential for the derivation of

  10. Derivation of porcine pluripotent stem cells for biomedical research.

    Science.gov (United States)

    Shiue, Yow-Ling; Yang, Jenn-Rong; Liao, Yu-Jing; Kuo, Ting-Yung; Liao, Chia-Hsin; Kang, Ching-Hsun; Tai, Chein; Anderson, Gary B; Chen, Lih-Ren

    2016-07-01

    Pluripotent stem cells including embryonic stem cells (ESCs), embryonic germ cells (EGCs), and induced pluripotent stem cells (iPSCs) are capable of self-renew and limitlessly proliferating in vitro with undifferentiated characteristics. They are able to differentiate in vitro, spontaneously or responding to suitable signals, into cells of all three primary germ layers. Consequently, these pluripotent stem cells will be valuable sources for cell replacement therapy in numerous disorders. However, the promise of human ESCs and EGCs is cramped by the ethical argument about destroying embryos and fetuses for cell line creation. Moreover, there are still carcinogenic risks existing toward the goal of clinical application for human ESCs, EGCs, and iPSCs. Therefore, a suitable animal model for stem cell research will benefit the further development of human stem cell technology. The pigs, on the basis of their similarity in anatomy, immunology, physiology, and biochemical properties, have been wide used as model animals in the study of various human diseases. The development of porcine pluripotent stem cell lines will hold the opportunity to provide an excellent material for human counterpart to the transplantation in biomedical research and further development of cell-based therapeutic strategy. PMID:27158128

  11. Induced pluripotent stem cells, from generation to application: review article

    Directory of Open Access Journals (Sweden)

    Sharif Moradi

    2014-11-01

    Full Text Available Embryonic stem cells are pluripotent stem cells which have the ability to indefinitely self-renew and differentiate into all differentiated cells of the body. Regarding their two main properties (unlimited self-renewal and multi-lineage differentiation, these cells have various biomedical applications in basic research and cell based therapy. Because the transplantation of differentiated cells that are derived from embryonic stem cells is allogenic, they face the problem of immune rejection following the transplantation of embryonic stem cell-derived cells into patients. In 2006, researchers from Japan reported the derivation of a new type of pluripotent stem cells which could overcome the problem of immune rejection that is associated with the application of embryonic stem cells. They designated these cells as induced pluripotent stem (iPS cells, because their production was ‘induced’ from differentiated somatic cells using a combination of four embryonic stem cell-associated transcription factors. Importantly, these pluripotent stem cells exhibit all the key features of embryonic stem cells including unlimited self-renewal and multi-lineage differentiation potential, and can pass the most stringent test of pluripotency which is known as the tetraploid (4n complementation. Hence, in addition to bypassing the problem of immune rejection, iPS cells have all of the potential applications of embryonic stem cells, including in developmental studies, toxicology research, drug discovery and disease modeling. Also, considering that they could be generated from patient’s own cells, iPS cells hold great promise in the future of patient-specific cell replacement therapies using pluripotent stem cells. In this review article, we will present a comprehensive review on the how and why of the generation of iPS cell from somatic cells of the body and discuss how they should be characterized in terms of morphologically, pluripotent stem cell behavior, and

  12. Transgene Reactivation in Induced Pluripotent Stem Cell Derivatives and Reversion to Pluripotency of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Galat, Vasiliy; Galat, Yekaterina; Perepitchka, Mariana; Jennings, Lawrence J; Iannaccone, Philip M; Hendrix, Mary J C

    2016-07-15

    Induced pluripotent stem cells (iPSCs) have enormous potential in regenerative medicine and disease modeling. It is now felt that clinical trials should be performed with iPSCs derived with nonintegrative constructs. Numerous studies, however, including those describing disease models, are still being published using cells derived from iPSCs generated with integrative constructs. Our experimental work presents the first evidence of spontaneous transgene reactivation in vitro in several cellular types. Our results show that the transgenes were predominantly silent in parent iPSCs, but in mesenchymal and endothelial iPSC derivatives, the transgenes experienced random upregulation of Nanog and c-Myc. Additionally, we provide evidence of spontaneous secondary reprogramming and reversion to pluripotency in mesenchymal stem cells derived from iPSCs. These findings strongly suggest that the studies, which use cellular products derived from iPSCs generated with retro- or lentiviruses, should be evaluated with consideration of the possibility of transgene reactivation. The in vitro model described here provides insight into the earliest events of culture transformation and suggests the hypothesis that reversion to pluripotency may be responsible for the development of tumors in cell replacement experiments. The main goal of this work, however, is to communicate the possibility of transgene reactivation in retro- or lenti-iPSC derivatives and the associated loss of cellular fidelity in vitro, which may impact the outcomes of disease modeling and related experimentation. PMID:27193052

  13. Decoding the architectural theory

    Institute of Scientific and Technical Information of China (English)

    Gu Mengchao

    2008-01-01

    Starting from the illustration of the definition and concept of the architectural theory, the author established his unique understanding about the framework of the architectural theory and the innovation of the architectural theory underlined by Chinese characteristics.

  14. Nitric Oxide And Hypoxia Response In Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Estefanía Caballano Infantes

    2015-08-01

    Full Text Available The expansion of pluripotent cells (ESCs and iPSCs under conditions that maintain their pluripotency is necessary to implement a cell therapy program. Previously, we have described that low nitric oxide (NO donor diethylenetriamine/nitric oxide adduct (DETA-NO added to the culture medium, promote the expansion of these cell types. The molecular mechanisms are not yet known. We present evidences that ESC and iPSCs in normoxia in presence of low NO triggers a similar response to hypoxia, thus maintaining the pluripotency. We have studied the stability of HIF-1α (Hypoxia Inducible Factor in presence of low NO. Because of the close relationship between hypoxia, metabolism, mitochondrial function and pluripotency we have analyzed by q RT-PCR the expression of genes involved in the glucose metabolism such as: HK2, LDHA and PDK1; besides other HIF-1α target gene. We further analyzed the expression of genes involved in mitochondrial biogenesis such as PGC1α, TFAM and NRF1 and we have observed that low NO maintains the same pattern of expression that in hypoxia. The study of the mitochondrial membrane potential using Mito-Tracker dye showed that NO decrease the mitochondrial function. We will analyze other metabolic parameters, to determinate if low NO regulates mitochondrial function and mimics Hypoxia Response. The knowledge of the role of NO in the Hypoxia Response and the mechanism that helps to maintain self-renewal in pluripotent cells in normoxia, can help to the design of culture media where NO could be optimal for stem cell expansion in the performance of future cell therapies.

  15. Pluripotent stem cells for the study of CNS development

    Directory of Open Access Journals (Sweden)

    Timothy J. Petros

    2011-10-01

    Full Text Available The mammalian central nervous system is a complex neuronal meshwork consisting of a diverse array of cellular subtypes generated in a precise spatial and temporal pattern throughout development. Achieving a greater understanding of the molecular and genetic mechanisms that direct a relatively uniform population of neuroepithelial progenitors into the diverse neuronal subtypes remains a significant challenge. A firmer knowledge of the fundamental aspects of developmental neuroscience will allow us to better study the vast array of neurodevelopmental diseases. The advent of stem cell technologies has expedited our ability to generate and isolate populations of distinct interneuron subtypes. To date, researchers have successfully developed protocols to derive many types of neural cells from pluripotent stem cells, with varying degrees of efficiencies and reproducibility. The stem cell field is devoted to the potential of stem cell-derived neurons for the treatment of disease, highlighted by the ability to create patient specific induced pluripotent stem cells. However, another application that is often overlooked is the use of stem cell technology for studying normal neural development. This is especially important for human neurodevelopment, since obtaining embryonic tissue presents numerous technical and ethical challenges. In this review, we will explore the use of pluripotent stem cells for the study of neural development. We will review the different classes of pluripotent stem cells and focus on the types of neurodevelopmental questions that stem cell technologies can help address. In addition to covering the different neural cells derived from stem cells to date, we will detail the derivation and characterization of three of the more thoroughly studied cell groups. We hope that this review encourages researchers to develop innovative strategies for using pluripotent stem cells for the study of mammalian, and specifically human

  16. Preserving Architectural Decisions through Architectural Patterns

    OpenAIRE

    Thon That, Minh Tu; Sadou, Salah; Oquendo, F.; Fleurquin, R

    2014-01-01

    International audience Architectural decisions have emerged as a means to maintain the quality of the architecture during its evolution. One of the most important de-cisions made by architects are those about the design approach such as the use of patterns or styles in the architecture. The structural nature of this type of decisions give them the potential to be controlled systematically. In the litera-ture, there are some works on the automation of architectural decision violation checki...

  17. Software Architecture Simulation

    OpenAIRE

    Mårtensson, Frans; Jönsson, Per

    2002-01-01

    A software architecture is one of the first steps towards a software system. A software architecture can be designed in different ways. During the design phase, it is important to select the most suitable design of the architecture, in order to create a good foundation for the system. The selection process is performed by evaluating architecture alternatives against each other. We investigate the use of continuous simulation of a software architecture as a support tool for architecture evalua...

  18. De lo con-céntrico a lo des-centrado. Reflexiones sobre el lugar y el no-lugar en la arquitectura. / From the concentric to the off-center. Reflections on the place and the non-place in architecture.

    Directory of Open Access Journals (Sweden)

    Laura Gallardo Frías

    2012-06-01

    Full Text Available Se propone, a través de la figura del círculo, abrir una reflexión sobre sus propiedades, su presencia y permanencia lo largo de la historia así como en nuestros días. Se invita al lector a un paseo por diferentes propuestas arquitectónicas y pensamientos paraexplorar el paso de lo con-céntrico a lo des-centrado, revisando las nociones de lugar, no-lugar y sus relaciones con la arquitectura. Poniendo de relieve la importancia del proyecto arquitectónico capaz de conformar centros donde el ser humano sea uno consigo mismo y loque le rodea, produciendo una profunda resonancia./ It is proposed, through the figure of the circle, opening a reflection on their properties, their presence and permanence throughout history and today. It invites the reader on a tour of different architectural proposals and thoughts to explore the transition from the con-centric to the ec-centric, reviewing the notions of place, non-place andits relationship with architecture. Emphasizing the importance of architecture as capable of forming centers where a human being with himself and his surroundings to produce a deep resonance.

  19. Architectures of prototypes and architectural prototyping

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius; Christensen, Michael; Sandvad, Elmer;

    1998-01-01

    sessions with users, - evolve over a long period of time to contain more functionality - allow for 6-7 developers working intensively in parallel. Explicit focus on the software architecture and letting the architecture evolve with the prototype played a major role in resolving these conflicting...... constraints. Specifically allowing explicit restructuring phases when the architecture became problematic showed to be crucial.  ...

  20. Software architecture 2

    CERN Document Server

    Oussalah, Mourad Chabanne

    2014-01-01

    Over the past 20 years, software architectures have significantly contributed to the development of complex and distributed systems. Nowadays, it is recognized that one of the critical problems in the design and development of any complex software system is its architecture, i.e. the organization of its architectural elements. Software Architecture presents the software architecture paradigms based on objects, components, services and models, as well as the various architectural techniques and methods, the analysis of architectural qualities, models of representation of architectural templa

  1. Lightweight enterprise architectures

    CERN Document Server

    Theuerkorn, Fenix

    2004-01-01

    STATE OF ARCHITECTUREArchitectural ChaosRelation of Technology and Architecture The Many Faces of Architecture The Scope of Enterprise Architecture The Need for Enterprise ArchitectureThe History of Architecture The Current Environment Standardization Barriers The Need for Lightweight Architecture in the EnterpriseThe Cost of TechnologyThe Benefits of Enterprise Architecture The Domains of Architecture The Gap between Business and ITWhere Does LEA Fit? LEA's FrameworkFrameworks, Methodologies, and Approaches The Framework of LEATypes of Methodologies Types of ApproachesActual System Environmen

  2. Software architecture 1

    CERN Document Server

    Oussalah , Mourad Chabane

    2014-01-01

    Over the past 20 years, software architectures have significantly contributed to the development of complex and distributed systems. Nowadays, it is recognized that one of the critical problems in the design and development of any complex software system is its architecture, i.e. the organization of its architectural elements. Software Architecture presents the software architecture paradigms based on objects, components, services and models, as well as the various architectural techniques and methods, the analysis of architectural qualities, models of representation of architectural template

  3. Building science of indian temple architecture

    OpenAIRE

    Vardia, Shweta

    2008-01-01

    Master’s Thesis Structural Analysis of Monuments and Historical Constructions Every style of building construction reflects a clearly distinctive basic principle that represents a particular culture and era. In this context the Indian Hindu temple architecture are not only the abode of God and place of worship, but they are also the cradle of knowledge, art, architecture and culture. The practices and traditions of temples exist not only in history but also in present time which g...

  4. Information architecture. Volume 1, The foundations

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-03-01

    The Information Management Planning and Architecture Coordinating Team was formed to establish an information architecture framework to meet DOE`s current and future information needs. This department- wide activity was initiated in accordance with the DOE Information Management Strategic Plan; it also supports the Departmental Strategic Plan. It recognizes recent changes in emphasis as reflected in OMB Circular A-130 and the Information Resources Management Planning Process Improvement Team recommendations. Sections of this document provides the foundation for establishing DOE`s Information Architecture: Background, Business Case (reduced duplication of effort, increased integration of activities, improved operational capabilities), Baseline (technology baseline currently in place within DOE), Vision (guiding principles for future DOE Information Architecture), Standards Process, Policy and Process Integration (describes relations between information architecture and business processes), and Next Steps. Following each section is a scenario. A glossary of terms is provided.

  5. Co-regulation of pluripotency and genetic integrity at the genomic level

    Directory of Open Access Journals (Sweden)

    Daniel J. Cooper

    2014-11-01

    Full Text Available The Disposable Soma Theory holds that genetic integrity will be maintained at more pristine levels in germ cells than in somatic cells because of the unique role germ cells play in perpetuating the species. We tested the hypothesis that the same concept applies to pluripotent cells compared to differentiated cells. Analyses of transcriptome and cistrome databases, along with canonical pathway analysis and chromatin immunoprecipitation confirmed differential expression of DNA repair and cell death genes in embryonic stem cells and induced pluripotent stem cells relative to fibroblasts, and predicted extensive direct and indirect interactions between the pluripotency and genetic integrity gene networks in pluripotent cells. These data suggest that enhanced maintenance of genetic integrity is fundamentally linked to the epigenetic state of pluripotency at the genomic level. In addition, these findings demonstrate how a small number of key pluripotency factors can regulate large numbers of downstream genes in a pathway-specific manner.

  6. Creating product line architectures

    OpenAIRE

    Bayer, J.; Flege, O.; Gacek, C.

    2000-01-01

    The creation and validation of product line software architectures are inherently more complex than those of software architectures for single systems. This paper compares a process for creating and evaluating a traditional, one-of-a- kind software architecture with one for a reference software architecture. The comparison is done in the context of PuLSE-DSSA, a customizable process that integrates both product line architecture creation and evaluation.

  7. ESA: Enterprise Service Architecture

    OpenAIRE

    2010-01-01

    The Service oriented perspective is emerging as an important view both for business architecture and IT architecture in the overall context of enterprise architectures. Many existing enterprise architecture frameworks like DODAF, MODAF and NAF have lately been extended with service-oriented views. The UPDM UML Profile and Metamodel for DODAF and MODAF has thus included various service-oriented views. This thesis proposes a new enterprise architecture framework ESA Enterprise Service Arch...

  8. In vitro regeneration of kidney from pluripotent stem cells

    International Nuclear Information System (INIS)

    Although renal transplantation has proved a successful treatment for the patients with end-stage renal failure, the therapy is hampered by the problem of serious shortage of donor organs. Regenerative medicine using stem cells, including cell transplantation therapy, needs to be developed to solve the problem. We previously identified the multipotent progenitor cells in the embryonic mouse kidney that can give rise to several kinds of epithelial cells found in adult kidney, such as glomerular podocytes and renal tubular epithelia. Establishing the method to generate the progenitors from human pluripotent stem cells that have the capacity to indefinitely proliferate in vitro is required for the development of kidney regeneration strategy. We review the current status of the research on the differentiation of pluripotent stem cells into renal lineages and describe cues to promote this research field.

  9. In vitro regeneration of kidney from pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Osafune, Kenji, E-mail: osafu@cira.kyoto-u.ac.jp [Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan); JST Yamanaka iPS Cell Special Project, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan)

    2010-10-01

    Although renal transplantation has proved a successful treatment for the patients with end-stage renal failure, the therapy is hampered by the problem of serious shortage of donor organs. Regenerative medicine using stem cells, including cell transplantation therapy, needs to be developed to solve the problem. We previously identified the multipotent progenitor cells in the embryonic mouse kidney that can give rise to several kinds of epithelial cells found in adult kidney, such as glomerular podocytes and renal tubular epithelia. Establishing the method to generate the progenitors from human pluripotent stem cells that have the capacity to indefinitely proliferate in vitro is required for the development of kidney regeneration strategy. We review the current status of the research on the differentiation of pluripotent stem cells into renal lineages and describe cues to promote this research field.

  10. Human Induced Pluripotent Stem Cell Models of Inherited Cardiovascular Diseases.

    Science.gov (United States)

    Jiang, Wenjian; Lan, Feng; Zhang, Hongjia

    2014-10-16

    Cardiovascular cells derived from patient specific induced Pluripotent Stem Cell (iPSC) harbor gene mutations associated with the pathogenesis of inherited cardiac diseases and congenital heart diseases (CHD). Numerous reports have demonstrated the utilization of human induced Pluripotent Stem Cell (hiPSC) to model cardiac diseases as a means of investigating their underlying mechanisms. So far, they have been shown to investigate the molecular mechanisms of many cardiac disorders, such as long-QT syndrome (LQT), catecholaminergic polymorphic ventricular tachycardia (CPVT), dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), LEOPARD syndrome (LS), arrhythmogenic cardiomyopathy (ACM), Friedreich ataxia (FRDA), Barth syndrome (BTHS), hypoplastic left heart syndrome (HLHS), Marfan syndrome (MFS) and other CHD. This article summarizes the growing body of research related to modeling various cardiac diseases using hiPSCs. Moreover, by reviewing the methods used in previous studies, we propose multiple novel applications of hiPSCs to investigate comprehensive cardiovascular disorders and facilitate drug discovery. PMID:25322695

  11. Identification and characterization of calcium sparks in cardiomyocytes derived from human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Guang Qin Zhang

    Full Text Available INTRODUCTION: Ca2+ spark constitutes the elementary units of cardiac excitation-contraction (E-C coupling in mature cardiomyocytes. Human induced pluripotent stem cell (hiPSC-derived cardiomyocytes are known to have electrophysiological properties similar to mature adult cardiomyocytes. However, it is unclear if they share similar calcium handling property. We hypothesized that Ca2+ sparks in human induced pluripotent stem cell (hiPSCs-derived cardiomyocytes (hiPSC-CMs may display unique structural and functional properties than mature adult cardiomyocytes. METHODS AND RESULTS: Ca2+ sparks in hiPSC-CMs were recorded with Ca2+ imaging assay with confocal laser scanning microscopy. Those sparks were stochastic with a tendency of repetitive occurrence at the same site. Nevertheless, the spatial-temporal properties of Ca2+ spark were analogous to that of adult CMs. Inhibition of L-type Ca2+ channels by nifedipine caused a 61% reduction in calcium spark frequency without affecting amplitude of those sparks and magnitude of caffeine releasable sarcoplasmic reticulum (SR Ca2+ content. In contrast, high extracellular Ca2+ and ryanodine increased the frequency, full width at half maximum (FWHM and full duration at half maximum (FDHM of spontaneous Ca2+ sparks. CONCLUSIONS: For the first time, spontaneous Ca2+ sparks were detected in hiPSC-CMs. The Ca2+ sparks are predominately triggered by L-type Ca2+ channels mediated Ca2+ influx, which is comparable to sparks detected in adult ventricular myocytes in which cardiac E-C coupling was governed by a Ca2+-induced Ca2+ release (CICR mechanism. However, focal repetitive sparks originated from the same intracellular organelle could reflect an immature status of the hiPSC-CMs.

  12. Characterizing the function of transcription factor 15 (Tcf15) in pluripotent cells

    OpenAIRE

    Lin, Chia-Yi

    2015-01-01

    Pluripotent embryonic stem (ES) cells are heterogeneous mixtures of naïve and lineage-primed states defined by distinct transcription factor expression profiles. However, the events that prime pluripotent cells for differentiation are not well understood. Id proteins, which are inhibitors of basic helix-loop-helix (bHLH) transcription factors, contribute to pluripotency by blocking differentiation. Using Yeast-Two-Hybrid screening, our lab identified Tcf15 as an Id-regulated...

  13. Generation of Induced Pluripotent Stem (iPS) Cells by Nuclear Reprogramming

    OpenAIRE

    Evans, Gregory R.D.; Dilip Dey

    2011-01-01

    During embryonic development pluripotency is progressively lost irreversibly by cell division, differentiation, migration and organ formation. Terminally differentiated cells do not generate other kinds of cells. Pluripotent stem cells are a great source of varying cell types that are used for tissue regeneration or repair of damaged tissue. The pluripotent stem cells can be derived from inner cell mass of blastocyte but its application is limited due to ethical concerns. The recent discovery...

  14. Derivation of Myogenic Progenitors Directly From Human Pluripotent Stem Cells Using a Sphere-Based Culture

    OpenAIRE

    Hosoyama, Tohru; McGivern, Jered V.; Van Dyke, Jonathan M.; Allison D Ebert; Suzuki, Masatoshi

    2014-01-01

    The authors present a novel protocol for deriving myogenic progenitors from human embryonic stem cells and induced pluripotent stem cells using free-floating spherical culture. Results show that sphere-based cultures of human pluripotent stem cells, expanded in medium containing high concentrations of fibroblast growth factor and epidermal growth factor, can propagate myogenic progenitors from human embryonic stem cells and healthy and disease-specific induced pluripotent stem cells.

  15. Induced pluripotent stem cells: Mechanisms, achievements and perspectives in farm animals

    OpenAIRE

    Kumar, Dharmendra; Talluri, Thirumala R; Anand, Taruna; Kues, Wilfried A.

    2015-01-01

    Pluripotent stem cells are unspecialized cells with unlimited self-renewal, and they can be triggered to differentiate into desired specialized cell types. These features provide the basis for an unlimited cell source for innovative cell therapies. Pluripotent cells also allow to study developmental pathways, and to employ them or their differentiated cell derivatives in pharmaceutical testing and biotechnological applications. Via blastocyst complementation, pluripotent cells are a favoured ...

  16. Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells

    OpenAIRE

    Patsch, Christoph; Challet-Meylan, Ludivine; Eva C Thoma; Urich, Eduard; Heckel, Tobias; O’Sullivan, John F.; Grainger, Stephanie J.; Kapp, Friedrich G.; Sun, Lin; Christensen, Klaus; Xia, Yulei; Florido, Mary H. C.; He, Wei; Pan, Wei; Prummer, Michael

    2015-01-01

    The use of human pluripotent stem cells for in vitro disease modeling and clinical applications requires protocols that convert these cells into relevant adult cell types. Here, we report the rapid and efficient differentiation of human pluripotent stem cells into vascular endothelial and smooth muscle cells. We found that GSK3 inhibition and BMP4 treatment rapidly committed pluripotent cells to a mesodermal fate and subsequent exposure to VEGF or PDGF-BB resulted in the differentiation of ei...

  17. Genome-wide chromatin interactions of the Nanog locus in pluripotency, differentiation and reprogramming

    OpenAIRE

    Apostolou, Effie; Ferrari, Francesco; Walsh, Ryan M.; Bar-Nur, Ori; Stadtfeld, Matthias; Cheloufi, Sihem; Stuart, Hannah T.; Polo, Jose M.; Ohsumi, Toshiro K.; Borowsky, Mark L.; Kharchenko, Peter V.; Park, Peter J.; Hochedlinger, Konrad

    2013-01-01

    While the chromatin state of pluripotency genes has been extensively studied in embryonic stem cells (ESCs) and differentiated cells, their potential interactions with other parts of the genome remain largely unexplored. Here, we identified a genome-wide, pluripotency-specific interaction network around the Nanog promoter by adapting circular chromosome conformation capture-sequencing (4C-seq). This network was rearranged during differentiation and restored in induced pluripotent stem cells. ...

  18. Human induced pluripotent stem cells on autologous feeders.

    Directory of Open Access Journals (Sweden)

    Kazutoshi Takahashi

    Full Text Available BACKGROUND: For therapeutic usage of induced Pluripotent Stem (iPS cells, to accomplish xeno-free culture is critical. Previous reports have shown that human embryonic stem (ES cells can be maintained in feeder-free condition. However, absence of feeder cells can be a hostile environment for pluripotent cells and often results in karyotype abnormalities. Instead of animal feeders, human fibroblasts can be used as feeder cells of human ES cells. However, one still has to be concerned about the existence of unidentified pathogens, such as viruses and prions in these non-autologous feeders. METHODOLOGY/PRINCIPAL FINDINGS: This report demonstrates that human induced Pluripotent Stem (iPS cells can be established and maintained on isogenic parental feeder cells. We tested four independent human skin fibroblasts for the potential to maintain self-renewal of iPS cells. All the fibroblasts tested, as well as their conditioned medium, were capable of maintaining the undifferentiated state and normal karyotypes of iPS cells. Furthermore, human iPS cells can be generated on isogenic parental fibroblasts as feeders. These iPS cells carried on proliferation over 19 passages with undifferentiated morphologies. They expressed undifferentiated pluripotent cell markers, and could differentiate into all three germ layers via embryoid body and teratoma formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that autologous fibroblasts can be not only a source for iPS cells but also be feeder layers. Our results provide a possibility to solve the dilemma by using isogenic fibroblasts as feeder layers of iPS cells. This is an important step toward the establishment of clinical grade iPS cells.

  19. Myogenic differentiation of FSHD patient specific induced pluripotent stem cells

    OpenAIRE

    Bosnakovski, Darko

    2012-01-01

    Human induced pluripotent stem (IPS) cells overcome several disadvantages of human embryonic stem cells, including host specificity and ethical issues. Patient-specific IPS cells can be generated from every donor by using different cell types, making them a suitable tool for autologous cell therapy and tissue engineering. IPS cells generated from patients with genetic disorders capture the disease genotype in the cell, making them a good model for studying the pathology of the diseas...

  20. Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2016-01-01

    Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease...... these diseases, but will lead to even more findings in the future as gene and cell culture technology continues to develop....

  1. Neural tissue engineering using embryonic and induced pluripotent stem cells

    OpenAIRE

    Willerth, Stephanie M.

    2011-01-01

    With the recent start of the first clinical trial evaluating a human embryonic stem cell-derived therapy for the treatment of acute spinal cord injury, it is important to review the current literature examining the use of embryonic stem cells for neural tissue engineering applications with a focus on diseases and disorders that affect the central nervous system. Embryonic stem cells exhibit pluripotency and thus can differentiate into any cell type found in the body, including those found in ...

  2. Citrullination regulates pluripotency and histone H1 binding to chromatin

    Science.gov (United States)

    Christophorou, Maria A.; Castelo-Branco, Gonçalo; Halley-Stott, Richard P.; Oliveira, Clara Slade; Loos, Remco; Radzisheuskaya, Aliaksandra; Mowen, Kerri A.; Bertone, Paul; Silva, José C. R.; Zernicka-Goetz, Magdalena; Nielsen, Michael L.; Gurdon, John B.; Kouzarides, Tony

    2014-03-01

    Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis. Nevertheless, the physiological functions of citrullination remain ill-defined, although citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction.

  3. Origination of the Protein Fold Repertoire from Oily Pluripotent Peptides

    OpenAIRE

    Mannige, Ranjan V.

    2014-01-01

    While the repertoire of protein folds that exists today underlies most of life’s capabilities, our mechanistic picture of protein fold origination is incomplete. This paper discusses a hypothetical mechanism for the emergence of the protein fold repertoire from highly dynamic and collapsed peptides, exemplified by peptides with high oil content or hydrophobicity. These peptides are called pluripotent to emphasize their capacity to evolve into numerous folds transiently available to them. As e...

  4. Induced Pluripotent Stem Cell Lines Derived from Equine Fibroblasts

    OpenAIRE

    Nagy, Kristina; Sung, Hoon-Ki; Zhang, Puzheng; Laflamme, Simon; Vincent, Patrick; Agha-Mohammadi, Siamak; Woltjen, Knut; Monetti, Claudio; Michael, Iacovos Prodromos; Smith, Lawrence Charles; Nagy, Andras

    2011-01-01

    The domesticated horse represents substantial value for the related sports and recreational fields, and holds enormous potential as a model for a range of medical conditions commonly found in humans. Most notable of these are injuries to muscles, tendons, ligaments and joints. Induced pluripotent stem (iPS) cells have sparked tremendous hopes for future regenerative therapies of conditions that today are not possible to cure. Equine iPS (EiPS) cells, in addition to bringing promises to the ve...

  5. Human Vascular Endothelium from Induced Pluripotent Stem Cells

    OpenAIRE

    Adams, William James

    2013-01-01

    The vascular endothelium is a dynamic cellular interface that displays a unique phenotypic plasticity. This plasticity is critical for vascular function and when dysregulated is pathogenic in several diseases. The development of new human endothelial genotype-phenotype studies, personalized vascular medicine efforts and cell based regenerative therapies are limited by the unavailability of patient-specific endothelial cells. Induced pluripotent stem cells (iPSC) offer great promise as a new p...

  6. Retinal Organoids from Pluripotent Stem Cells Efficiently Recapitulate Retinogenesis

    OpenAIRE

    Manuela Völkner; Marlen Zschätzsch; Maria Rostovskaya; Rupert W. Overall; Volker Busskamp; Konstantinos Anastassiadis; Mike O. Karl

    2016-01-01

    Summary The plasticity of pluripotent stem cells provides new possibilities for studying development, degeneration, and regeneration. Protocols for the differentiation of retinal organoids from embryonic stem cells have been developed, which either recapitulate complete eyecup morphogenesis or maximize photoreceptor genesis. Here, we have developed a protocol for the efficient generation of large, 3D-stratified retinal organoids that does not require evagination of optic-vesicle-like structur...

  7. Pathways in pluripotency and differentiation of embryonic cells

    OpenAIRE

    du Puy, L.

    2010-01-01

    Pluripotency - the potential to differentiate into derivatives of the three embryonic germ layers endoderm, ectoderm and mesoderm - is the main characteristic of embryonic stem (ES) cells. ES cells are derived from the inner cell mass (ICM) of a pre-implantation blastocyst and can self-renew indefinitely in culture. Because of their differentiation capabilities, ES cells can potentially be used in cell-based therapies in human medicine as well as for toxicology screening and drug testing. Mor...

  8. Induced Pluripotent Stem Cells for Neural Tissue Engineering

    OpenAIRE

    Wang, Aijun; Tang, Zhenyu; Park, In-Hyun; Zhu, Yiqian; Patel, Shyam; Daley, George Q.; Song, Li

    2011-01-01

    Induced pluripotent stem cells (iPSCs) hold great promise for cell therapies and tissue engineering. Neural crest stem cells (NCSCs) are multipotent and represent a valuable system to investigate iPSC differentiation and therapeutic potential. Here we derived NCSCs from human iPSCs and embryonic stem cells (ESCs), and investigated the potential of NCSCs for neural tissue engineering. The differentiation of iPSCs and the expansion of derived NCSCs varied in different cell lines, but all NCSC l...

  9. Dynamic instability of genomic methylation patterns in pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Ooi Steen KT

    2010-09-01

    Full Text Available Abstract Background Genomic methylation patterns are established during gametogenesis, and perpetuated in somatic cells by faithful maintenance methylation. There have been previous indications that genomic methylation patterns may be less stable in embryonic stem (ES cells than in differentiated somatic cells, but it is not known whether different mechanisms of de novo and maintenance methylation operate in pluripotent stem cells compared with differentiating somatic cells. Results In this paper, we show that ablation of the DNA methyltransferase regulator DNMT3L (DNA methyltransferase 3-like in mouse ES cells renders them essentially incapable of de novo methylation of newly integrated retroviral DNA. We also show that ES cells lacking DNMT3L lose DNA methylation over time in culture, suggesting that DNA methylation in ES cells is the result of dynamic loss and gain of DNA methylation. We found that wild-type female ES cells lose DNA methylation at a much faster rate than do male ES cells; this defect could not be attributed to sex-specific differences in expression of DNMT3L or of any DNA methyltransferase. We also found that human ES and induced pluripotent stem cell lines showed marked but variable loss of methylation that could not be attributed to sex chromosome constitution or time in culture. Conclusions These data indicate that DNA methylation in pluripotent stem cells is much more dynamic and error-prone than is maintenance methylation in differentiated cells. DNA methylation requires DNMT3L in stem cells, but DNMT3L is not expressed in differentiating somatic cells. Error-prone maintenance methylation will introduce unpredictable phenotypic variation into clonal populations of pluripotent stem cells, and this variation is likely to be much more pronounced in cultured female cells. This epigenetic variability has obvious negative implications for the clinical applications of stem cells.

  10. Modelling familial dysautonomia in human induced pluripotent stem cells

    OpenAIRE

    Lee, Gabsang; Studer, Lorenz

    2011-01-01

    Induced pluripotent stem (iPS) cells have considerable promise as a novel tool for modelling human disease and for drug discovery. While the generation of disease-specific iPS cells has become routine, realizing the potential of iPS cells in disease modelling poses challenges at multiple fronts. Such challenges include selecting a suitable disease target, directing the fate of iPS cells into symptom-relevant cell populations, identifying disease-related phenotypes and showing reversibility of...

  11. Reflection groups

    International Nuclear Information System (INIS)

    In 2005, PISA organised proactive meetings of reflection groups on involvement in decision making, expert culture and ethical aspects of radiation protection.All reflection group meetings address particular targeted audiences while the output publication in book form is put forward

  12. Regeneration of tracheal epithelium using mouse induced pluripotent stem cells.

    Science.gov (United States)

    Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Otsuki, Koshi; Miyake, Masao; Hazama, Akihiro; Wada, Ikuo; Omori, Koichi

    2016-04-01

    Conclusion The findings demonstrated the potential use of induced pluripotent stem cells for regeneration of tracheal epithelium. Objective Autologous tissue implantation techniques using skin or cartilage are often applied in cases of tracheal defects with laryngeal inflammatory lesions and malignant tumor invasion. However, these techniques are invasive with an unstable clinical outcome. The purpose of this study was to investigate regeneration in a tracheal defect site of nude rats after implantation of ciliated epithelium that was differentiated from induced pluripotent stem cells. Method Embryoid bodies were formed from mouse induced pluripotent stem cells. They were cultured with growth factors for 5 days, and then cultured at the air-liquid interface. The degree of differentiation achieved prior to implantation was determined by histological findings and the results of real-time polymerase chain reaction. Embryoid bodies including ciliated epithelium were embedded into collagen gel that served as an artificial scaffold, and then implanted into nude rats, creating an 'air-liquid interface model'. Histological evaluation was performed 7 days after implantation. Results The ciliated epithelial structure survived on the lumen side of regenerated tissue. It was demonstrated histologically that the structure was composed of ciliated epithelial cells. PMID:26755348

  13. Human pluripotent stem cell culture density modulates YAP signaling.

    Science.gov (United States)

    Hsiao, Cheston; Lampe, Michael; Nillasithanukroh, Songkhun; Han, Wenqing; Lian, Xiaojun; Palecek, Sean P

    2016-05-01

    Human pluripotent stem cell (hPSC) density is an important factor in self-renewal and differentiation fates; however, the mechanisms through which hPSCs sense cell density and process this information in making cell fate decisions remain to be fully understood. One particular pathway that may prove important in density-dependent signaling in hPSCs is the Hippo pathway, which is regulated by cell-cell contact and mechanosensing through the cytoskeleton and has been linked to the maintenance of stem cell pluripotency. To probe regulation of Hippo pathway activity in hPSCs, we assessed whether Hippo pathway transcriptional activator YAP was differentially modulated by cell density. At higher cell densities, YAP phosphorylation and localization to the cytoplasm increased, which led to decreased YAP-mediated transcriptional activity. Furthermore, total YAP protein levels diminished at high cell density due to the phosphorylation-targeted degradation of YAP. Inducible shRNA knockdown of YAP reduced expression of YAP target genes and pluripotency genes. Finally, the density-dependent increase of neuroepithelial cell differentiation was mitigated by shRNA knockdown of YAP. Our results suggest a pivotal role of YAP in cell density-mediated fate decisions in hPSCs. PMID:26766309

  14. Tumorigenicity studies for human pluripotent stem cell-derived products.

    Science.gov (United States)

    Kuroda, Takuya; Yasuda, Satoshi; Sato, Yoji

    2013-01-01

    Human pluripotent stem cells (hPSCs), i.e. human embryonic stem cells and human induced pluripotent stem cells, are able to self-renew and differentiate into multiple cell types. Because of these abilities, numerous attempts have been made to utilize hPSCs in regenerative medicine/cell therapy. hPSCs are, however, also tumorigenic, that is, they can give rise to the progressive growth of tumor nodules in immunologically unresponsive animals. Therefore, assessing and managing the tumorigenicity of all final products is essential in order to prevent ectopic tissue formation, tumor development, and/or malignant transformation elicited by residual pluripotent stem cells after implantation. No detailed guideline for the tumorigenicity testing of hPSC-derived products has yet been issued for regenerative medicine/cell therapy, despite the urgent necessity. Here, we describe the current situations and issues related to the tumorigenicity testing of hPSC-derived products and we review the advantages and disadvantages of several types of tumorigenicity-associated tests. We also refer to important considerations in the execution and design of specific studies to monitor the tumorigenicity of hPSC-derived products. PMID:23370350

  15. The Use of Pluripotent Stem Cell for Personalized Cell Therapies against Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Hye-Yeong Ha

    2011-01-01

    Full Text Available Although there are a number of weaknesses for clinical use, pluripotent stem cells are valuable sources for patient-specific cell therapies against various diseases. Backed-up by a huge number of basic researches, neuronal differentiation mechanism is well established and pluripotent stem cell therapies against neurological disorders are getting closer to clinical application. However, there are increasing needs for standardization of the sourcing pluripotent stem cells by establishing stem cell registries and banking. Global harmonization will accelerate practical use of personalized therapies using pluripotent stem cells.

  16. Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206

    KAUST Repository

    Liang, Yu

    2012-06-26

    Zfp206 (also named as Zscan10) belongs to the subfamily of C2H2 zinc finger transcription factors, which is characterized by the N-terminal SCAN domain. The SCAN domain mediates self-association and association between the members of SCAN family transcription factors, but the structural basis and selectivity determinants for complex formation is unknown. Zfp206 is important for maintaining the pluripotency of embryonic stem cells presumably by combinatorial assembly of itself or other SCAN family members on enhancer regions. To gain insights into the folding topology and selectivity determinants for SCAN dimerization, we solved the 1.85 crystal structure of the SCAN domain of Zfp206. In vitro binding studies using a panel of 20 SCAN proteins indicate that the SCAN domain Zfp206 can selectively associate with other members of SCAN family transcription factors. Deletion mutations showed that the N-terminal helix 1 is critical for heterodimerization. Double mutations and multiple mutations based on the Zfp206SCAN-Zfp110SCAN model suggested that domain swapped topology is a possible preference for Zfp206SCAN-Zfp110SCAN heterodimer. Together, we demonstrate that the Zfp206SCAN constitutes a protein module that enables C2H2 transcription factor dimerization in a highly selective manner using a domain-swapped interface architecture and identify novel partners for Zfp206 during embryonal development. 2012 The Author(s).

  17. E-Business Security Architectures

    Directory of Open Access Journals (Sweden)

    2009-01-01

    Full Text Available By default the Internet is an open high risk environment and also the main place where the e-business is growing. As result of this fact, the paper aims to highlight the security aspects that relate to distributed applications [3], with reference to the concept of e-business. In this direction will analyze the quality characteristics, considered to be important by the author. Based on these and on existing e-business architectures will be presented a particularly diagram which will reflect a new approach to the concept of future e-business. The development of the new architecture will have its stands based on technologies that are used to build the applications of tomorrow.

  18. Rhein-Ruhr architecture

    DEFF Research Database (Denmark)

    2002-01-01

    katalog til udstillingen 'Rhein - Ruhr architecture' Meldahls smedie, 15. marts - 28. april 2002. 99 sider......katalog til udstillingen 'Rhein - Ruhr architecture' Meldahls smedie, 15. marts - 28. april 2002. 99 sider...

  19. Bioclimatism in vernacular architecture

    OpenAIRE

    Coch Roura, Helena

    1998-01-01

    Any analysis of the role played by energy in architecture is faced with serious limitations due to the lack of studies in the architectural bibliography, especially studies of popular architecture. An awareness of these limitations will allow us to understand better why architects have paid little attention to the interaction of form and energy, and to the bioclimatic approach in contemporary architecture in general. The first limitation stems from the very essence of bioclimatic analysis; en...

  20. Controller Architectures for Switching

    DEFF Research Database (Denmark)

    Niemann, Hans Henrik; Poulsen, Niels Kjølstad

    2009-01-01

    This paper investigate different controller architectures in connection with controller switching. The controller switching is derived by using the Youla-Jabr-Bongiorno-Kucera (YJBK) parameterization. A number of different architectures for the implementation of the YJBK parameterization are...... described and applied in connection with controller switching. An architecture that does not include inversion of the coprime factors is introduced. This architecture will make controller switching particular simple....

  1. Minimalist Architecture; Discussion of Its Sustainability in Indonesia

    OpenAIRE

    Silfia Mona Aryani

    2011-01-01

    Architecture develops along with particular society changing. In the period of modern, some traditional architecture with their complex rules become considered old fashioned. It was not implemented in modern buildings. When functionality becomes priority, minimalist architecture, recognized as Neo-Modernism, spreads and offers reflection of modern lifestyle. However, every style is not always suitable for each circumstance. The unconditional application of style can create another problem ins...

  2. An event-based architecture for solving constraint satisfaction problems

    OpenAIRE

    Mostafa, Hesham; Müller, Lorenz K.; Indiveri, Giacomo

    2015-01-01

    Constraint satisfaction problems (CSPs) are typically solved using conventional von Neumann computing architectures. However, these architectures do not reflect the distributed nature of many of these problems and are thus ill-suited to solving them. In this paper we present a hybrid analog/digital hardware architecture specifically designed to solve such problems. We cast CSPs as networks of stereotyped multi-stable oscillatory elements that communicate using digital pulses, or events. The o...

  3. Tourists' Transformation Experience: From Destination Architecture to Identity Formation

    DEFF Research Database (Denmark)

    Ye, Helen Yi; Tussyadiah, Iis

    2010-01-01

    Today’s tourists seek unique destinations that could associate with their self identity in a profound way. It is meaningful for destinations to design unique physical elements that offer transformational travel experiences. This study aims at identifying how tourists encounter architecture in a...... destination and if architecture facilitates tourists’ self transformation. Based on narrative structure analysis by deconstruction of travel blog posts, the results suggest that tourists perceive architectural landscape as an important feature that reflects destinations’ identity. Four different interaction...

  4. School of Architecture + Design establishes Virginia Tech architecture publications

    OpenAIRE

    Chadwick, Heather Riley

    2007-01-01

    Virginia Tech's School of Architecture + Design, in the College of Architecture and Urban Studies, with the initiative of Markus Breitschmid, assistant professor of architecture, has established Virginia Tech Architecture Publications.

  5. Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells.

    Directory of Open Access Journals (Sweden)

    Megan G Massa

    Full Text Available As multiple sclerosis research progresses, it is pertinent to continue to develop suitable paradigms to allow for ever more sophisticated investigations. Animal models of multiple sclerosis, despite their continuing contributions to the field, may not be the most prudent for every experiment. Indeed, such may be either insufficient to reflect the functional impact of human genetic variations or unsuitable for drug screenings. Thus, we have established a cell- and patient-specific paradigm to provide an in vitro model within which to perform future genetic investigations. Renal proximal tubule epithelial cells were isolated from multiple sclerosis patients' urine and transfected with pluripotency-inducing episomal factors. Subsequent induced pluripotent stem cells were formed into embryoid bodies selective for ectodermal lineage, resulting in neural tube-like rosettes and eventually neural progenitor cells. Differentiation of these precursors into primary neurons was achieved through a regimen of neurotrophic and other factors. These patient-specific primary neurons displayed typical morphology and functionality, also staining positive for mature neuronal markers. The development of such a non-invasive procedure devoid of permanent genetic manipulation during the course of differentiation, in the context of multiple sclerosis, provides an avenue for studies with a greater cell- and human-specific focus, specifically in the context of genetic contributions to neurodegeneration and drug discovery.

  6. Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

    Science.gov (United States)

    Massa, Megan G.; Gisevius, Barbara; Hirschberg, Sarah; Hinz, Lisa; Schmidt, Matthias; Gold, Ralf; Prochnow, Nora; Haghikia, Aiden

    2016-01-01

    As multiple sclerosis research progresses, it is pertinent to continue to develop suitable paradigms to allow for ever more sophisticated investigations. Animal models of multiple sclerosis, despite their continuing contributions to the field, may not be the most prudent for every experiment. Indeed, such may be either insufficient to reflect the functional impact of human genetic variations or unsuitable for drug screenings. Thus, we have established a cell- and patient-specific paradigm to provide an in vitro model within which to perform future genetic investigations. Renal proximal tubule epithelial cells were isolated from multiple sclerosis patients’ urine and transfected with pluripotency-inducing episomal factors. Subsequent induced pluripotent stem cells were formed into embryoid bodies selective for ectodermal lineage, resulting in neural tube-like rosettes and eventually neural progenitor cells. Differentiation of these precursors into primary neurons was achieved through a regimen of neurotrophic and other factors. These patient-specific primary neurons displayed typical morphology and functionality, also staining positive for mature neuronal markers. The development of such a non-invasive procedure devoid of permanent genetic manipulation during the course of differentiation, in the context of multiple sclerosis, provides an avenue for studies with a greater cell- and human-specific focus, specifically in the context of genetic contributions to neurodegeneration and drug discovery. PMID:27158987

  7. Presumed pluripotency markers UTF-1 and REX-1 are expressed in human adult testes and germ cell neoplasms

    DEFF Research Database (Denmark)

    Kristensen, David M; Nielsen, John E; Skakkebaek, Niels E;

    2008-01-01

    UTF-1 and REX-1/ZFP42 are transcription factors involved in pluripotency. Because of phenotypic similarities between pluripotent embryonic stem cells and testicular germ cell tumours (TGCT) and the derivation of pluripotent cells from testes, we investigated the expression of UTF-1 and REX-1 duri...

  8. Presumed pluripotency markers UTF-1 and REX-1 are expressed in human adult testes and germ cell neoplasms

    DEFF Research Database (Denmark)

    Kristensen, D.M.; Nielsen, J.E.; Skakkebaek, N.E.;

    2008-01-01

    BACKGROUND: UTF-1 and REX-1/ZFP42 are transcription factors involved in pluripotency. Because of phenotypic similarities between pluripotent embryonic stem cells and testicular germ cell tumours (TGCT) and the derivation of pluripotent cells from testes, we investigated the expression of UTF-1 an...

  9. “Mouse Clone Model” for evaluating the immunogenicity and tumorigenicity of pluripotent stem cells

    OpenAIRE

    Zhang, Gang; Zhang, Yi

    2015-01-01

    To investigate the immune-rejection and tumor-formation potentials of induced pluripotent stem cells and other stem cells, we devised a model—designated the “Mouse Clone Model”—which combined the theory of somatic animal cloning, tetraploid complementation, and induced pluripotent stem cells to demonstrate the applicability of stem cells for transplantation therapy.

  10. Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance

    DEFF Research Database (Denmark)

    Fort, Alexandre; Hashimoto, Kosuke; Yamada, Daisuke; Salimullah, Md; Keya, Chaman A.; Saxena, Alka; Bonetti, Alessandro; Voineagu, Irina; Bertin, Nicolas; Kratz, Anton; Noro, Yukihiko; Wong, Chee-Hong; de Hoon, Michiel; Andersson, Robin; Sandelin, Albin Gustav; Suzuki, Harukazu; Wei, Chia-Lin; Koseki, Haruhiko; Hasegawa, Yuki; Forrest, Alistair R R; Carninci, Piero

    2014-01-01

    The importance of microRNAs and long noncoding RNAs in the regulation of pluripotency has been documented; however, the noncoding components of stem cell gene networks remain largely unknown. Here we investigate the role of noncoding RNAs in the pluripotent state, with particular emphasis on nucl...

  11. Comparison of American mink embryonic stem and induced pluripotent stem cell transcriptomes

    DEFF Research Database (Denmark)

    Menzorov, Aleksei G; Matveeva, Natalia M.; Markakis, Marios Nektarios;

    2015-01-01

    PS cell lines. The majority of the analyzed cell lines had normal diploid chromosome number. The only ES cell line with XX chromosome set had both X-chromosomes in active state that is characteristic of pluripotent cells. The pluripotency of ES and iPS cell lines was confirmed by formation of teratomas...

  12. Apoptotic Susceptibility to DNA Damage of Pluripotent Stem Cells Facilitates Pharmacologic Purging of Teratoma Risk

    OpenAIRE

    Smith, Alyson J.; Nelson, Natalie G.; Oommen, Saji; Hartjes, Katherine A.; Folmes, Clifford D.; Terzic, Andre; Nelson, Timothy J.

    2012-01-01

    The pluripotent cell-purging assay validated herein demonstrates that pluripotent cells are selectively hypersensitive to DNA damage-induced apoptosis as a function of the specific apoptotic inducer protein Puma. Risk of dysregulated growth is decreased and the safety profile of transplant-ready, bioengineered progenitor cells is augmented.

  13. Architectural Knitted Surfaces

    DEFF Research Database (Denmark)

    Mossé, Aurélie

    2010-01-01

    WGSN reports from the Architectural Knitted Surfaces workshop recently held at ShenkarCollege of Engineering and Design, Tel Aviv, which offered a cutting-edge insight into interactive knitted surfaces. With the increasing role of smart textiles in architecture, the Architectural Knitted Surfaces...

  14. Language-based support for service oriented architectures

    DEFF Research Database (Denmark)

    Giambiagi, Pablo; Owe, Olaf; Ravn, Anders Peter;

    2006-01-01

    The fast evolution of the Internet has popularized service-oriented architectures (SOA) with their promise of dynamic IT-supported inter-business collaborations. Yet this popularity does not reflect on the number of actual applications using the architecture. Programming models in use today make ...

  15. Reflective State Pattern with Dynamic Constructiveness

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    After discussing the reflective method of structure and behaviorin th e State design pattern based on Role Object pattern and the Reflective pattern o f software architecture, this paper proposes a reflective state pattern with dyn amic constructiveness. This paper explains the meta level and the base level, wh ich are two levels of this pattern, and specifies the relation of two levels by using Meta Object Protocol (MOP). Then it discusses mechanism of interception an d reification for reflecting base object from Meta object. Finally this paper g ives an example of network server for applying the Reflective State pattern

  16. Sox2, a key factor in the regulation of pluripotency and neural differentiation

    Institute of Scientific and Technical Information of China (English)

    Shuchen; Zhang; Wei; Cui

    2014-01-01

    Sex determining region Y-box 2(Sox2), a member of the SoxB1 transcription factor family, is an important transcriptional regulator in pluripotent stem cells(PSCs). Together with octamer-binding transcription factor 4 and Nanog, they co-operatively control gene expression in PSCs and maintain their pluripotency. Furthermore, Sox2 plays an essential role in somatic cell reprogram-ming, reversing the epigenetic configuration of differ-entiated cells back to a pluripotent embryonic state. In addition to its role in regulation of pluripotency, Sox2 is also a critical factor for directing the differentiation of PSCs to neural progenitors and for maintaining the properties of neural progenitor stem cells. Here, we review recent findings concerning the involvement of Sox2 in pluripotency, somatic cell reprogramming and neural differentiation as well as the molecular mecha-nisms underlying these roles.

  17. Software Architecture Viewpoint Models: A Short Survey

    Directory of Open Access Journals (Sweden)

    Seyyed Ali Razavi Ebrahimi

    2013-11-01

    Full Text Available A software architecture is a complex entity that cannot be described in a simple one-dimensional fashion. The architecture views used to describe software provide the architect with a means of explaining the architecture to stakeholders. Each view presents different aspects of the system that fulfill functional and non-functional requirements. A view of a system is a representation of the system from the perspective of a viewpoint. Architecture viewpoints in software products provide guidelines to describe uniformly the total system and its subsystems. It defines the stakeholders whose concerns are reflected in the viewpoint and the guidelines, principles, and template models for constructing its views. The results of this study may serve as a roadmap to the software developers and architects in helping them select the appropriate viewpoint model based on the stakeholders and concerns that need to be covered by views.

  18. Reprogramming to pluripotency can conceal somatic cell chromosomal instability.

    Directory of Open Access Journals (Sweden)

    Masakazu Hamada

    Full Text Available The discovery that somatic cells are reprogrammable to pluripotency by ectopic expression of a small subset of transcription factors has created great potential for the development of broadly applicable stem-cell-based therapies. One of the concerns regarding the safe use of induced pluripotent stem cells (iPSCs in therapeutic applications is loss of genomic integrity, a hallmark of various human conditions and diseases, including cancer. Structural chromosome defects such as short telomeres and double-strand breaks are known to limit reprogramming of somatic cells into iPSCs, but whether defects that cause whole-chromosome instability (W-CIN preclude reprogramming is unknown. Here we demonstrate, using aneuploidy-prone mouse embryonic fibroblasts (MEFs in which chromosome missegregation is driven by BubR1 or RanBP2 insufficiency, that W-CIN is not a barrier to reprogramming. Unexpectedly, the two W-CIN defects had contrasting effects on iPSC genomic integrity, with BubR1 hypomorphic MEFs almost exclusively yielding aneuploid iPSC clones and RanBP2 hypomorphic MEFs karyotypically normal iPSC clones. Moreover, BubR1-insufficient iPSC clones were karyotypically unstable, whereas RanBP2-insufficient iPSC clones were rather stable. These findings suggest that aneuploid cells can be selected for or against during reprogramming depending on the W-CIN gene defect and present the novel concept that somatic cell W-CIN can be concealed in the pluripotent state. Thus, karyotypic analysis of somatic cells of origin in addition to iPSC lines is necessary for safe application of reprogramming technology.

  19. A highly efficient method for generation of therapeutic quality human pluripotent stem cells by using naive induced pluripotent stem cells nucleus for nuclear transfer

    OpenAIRE

    Sanal, Madhusudana Girija

    2014-01-01

    Even after several years since the discovery of human embryonic stem cells and induced pluripotent stem cells (iPSC), we are still unable to make any significant therapeutic benefits out of them such as cell therapy or generation of organs for transplantation. Recent success in somatic cell nuclear transfer (SCNT) made it possible to generate diploid embryonic stem cells, which opens up the way to make high-quality pluripotent stem cells. However, the process is highly inefficient and hence e...

  20. Evolution of plant genome architecture.

    Science.gov (United States)

    Wendel, Jonathan F; Jackson, Scott A; Meyers, Blake C; Wing, Rod A

    2016-01-01

    We have witnessed an explosion in our understanding of the evolution and structure of plant genomes in recent years. Here, we highlight three important emergent realizations: (1) that the evolutionary history of all plant genomes contains multiple, cyclical episodes of whole-genome doubling that were followed by myriad fractionation processes; (2) that the vast majority of the variation in genome size reflects the dynamics of proliferation and loss of lineage-specific transposable elements; and (3) that various classes of small RNAs help shape genomic architecture and function. We illustrate ways in which understanding these organism-level and molecular genetic processes can be used for crop plant improvement. PMID:26926526

  1. Reflective optics

    CERN Document Server

    Korsch, Dietrich

    1991-01-01

    This is the first book dedicated exclusively to all-reflective imaging systems. It is a teaching tool as well as a practical design tool for anyone who specializes in optics, particularly for those interested in telescopes, infrared, and grazing-incidence systems. The first part of the book describes a unified geometric optical theory of all-reflective imaging systems (from near-normal to grazing incidence) developed from basic principles. The second part discusses correction methods and a multitude of closed-form solutions of well-corrected systems, supplemented with many conventional and unc

  2. Human pluripotent stem cell models of Fragile X syndrome.

    Science.gov (United States)

    Bhattacharyya, Anita; Zhao, Xinyu

    2016-06-01

    Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism. The causal mutation in FXS is a trinucleotide CGG repeat expansion in the FMR1 gene that leads to human specific epigenetic silencing and loss of Fragile X Mental Retardation Protein (FMRP) expression. Human pluripotent stem cells (PSCs), including human embryonic stem cells (ESCs) and particularly induced PSCs (iPSCs), offer a model system to reveal cellular and molecular events underlying human neuronal development and function in FXS. Human FXS PSCs have been established and have provided insight into the epigenetic silencing of the FMR1 gene as well as aspects of neuronal development. PMID:26640241

  3. Software architecture evolution

    DEFF Research Database (Denmark)

    Barais, Olivier; Le Meur, Anne-Francoise; Duchien, Laurence;

    2008-01-01

    Software architectures must frequently evolve to cope with changing requirements, and this evolution often implies integrating new concerns. Unfortunately, when the new concerns are crosscutting, existing architecture description languages provide little or no support for this kind of evolution....... The software architect must modify multiple elements of the architecture manually, which risks introducing inconsistencies. This chapter provides an overview, comparison and detailed treatment of the various state-of-the-art approaches to describing and evolving software architectures. Furthermore, we...... discuss one particular framework named Tran SAT, which addresses the above problems of software architecture evolution. Tran SAT provides a new element in the software architecture descriptions language, called an architectural aspect, for describing new concerns and their integration into an existing...

  4. Heterozygous and homozygous JAK2(V617F states modeled by induced pluripotent stem cells from myeloproliferative neoplasm patients.

    Directory of Open Access Journals (Sweden)

    Joseph Saliba

    Full Text Available JAK2(V617F is the predominant mutation in myeloproliferative neoplasms (MPN. Modeling MPN in a human context might be helpful for the screening of molecules targeting JAK2 and its intracellular signaling. We describe here the derivation of induced pluripotent stem (iPS cell lines from 2 polycythemia vera patients carrying a heterozygous and a homozygous mutated JAK2(V617F, respectively. In the patient with homozygous JAK2(V617F, additional ASXL1 mutation and chromosome 20 allowed partial delineation of the clonal architecture and assignation of the cellular origin of the derived iPS cell lines. The marked difference in the response to erythropoietin (EPO between homozygous and heterozygous cell lines correlated with the constitutive activation level of signaling pathways. Strikingly, heterozygous iPS cells showed thrombopoietin (TPO-independent formation of megakaryocytic colonies, but not EPO-independent erythroid colony formation. JAK2, PI3K and HSP90 inhibitors were able to block spontaneous and EPO-induced growth of erythroid colonies from GPA(+CD41(+ cells derived from iPS cells. Altogether, this study brings the proof of concept that iPS can be used for studying MPN pathogenesis, clonal architecture, and drug efficacy.

  5. Tackling the epigenome in the pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Zhao; Yijun Ruan; Chia-Lin Wei

    2008-01-01

    Embryonic stem cells are unique in their abilities of self-renewal and to differentiate into many, if not all, cellular lineages. Transcrip- tional regulation, epigenetic modifications and chromatin structures are the key modulators in controlling such pluripotency nature of embryonic stem cell genomes, particularly in the developmental decisions and the maintenance of cell fates. Among them, epigenetic regulation of gene expression is mediated partly by covalent modifications of core histone proteins including methylation, phosphoryla- tion and acetylation. Moreover, the chromatins in stem cell genome appear as a highly organized structure containing distinct functional domains. Recent rapid progress of new technologies enables us to take a global, unbiased and comprehensive view of the epigenetic modifications and chromatin structures that contribute to gene expression regulation and cell identity during diverse developmental stages. Here, we summarized the latest advances made by high throughput approaches in profiling epigenetic modifications and chromatin con- formations, with an emphasis on genome-wide analysis of histone modifications and their implications in pluripotency nature of embry- onic stem cells.

  6. Concise review: programming human pluripotent stem cells into blood.

    Science.gov (United States)

    Easterbrook, Jennifer; Fidanza, Antonella; Forrester, Lesley M

    2016-06-01

    Blood disorders are treated with cell therapies including haematopoietic stem cell (HSC) transplantation as well as platelet and red blood cell transfusions. However the source of cells is entirely dependent on donors, procedures are susceptible to transfusion-transmitted infections and serious complications can arise in recipients due to immunological incompatibility. These problems could be alleviated if it was possible to produce haematopoietic cells in vitro from an autologous and renewable cell source. The production of haematopoietic cells in the laboratory from human induced pluripotent stem cells (iPSCs) may provide a route to realize this goal but it has proven challenging to generate long-term reconstituting HSCs. To date, the optimization of differentiation protocols has mostly relied on the manipulation of extrinsic signals to mimic the in vivo environment. We review studies that have taken an alternative approach to modulate intrinsic signals by enforced expression of transcription factors. Single and combinations of multiple transcription factors have been used in a variety of contexts to enhance the production of haematopoietic cells from human pluripotent stem cells. This programming approach, together with the recent advances in the production and use of synthetic transcription factors, holds great promise for the production of fully functional HSCs in the future. PMID:26996518

  7. hPSCreg--the human pluripotent stem cell registry.

    Science.gov (United States)

    Seltmann, Stefanie; Lekschas, Fritz; Müller, Robert; Stachelscheid, Harald; Bittner, Marie-Sophie; Zhang, Weiping; Kidane, Luam; Seriola, Anna; Veiga, Anna; Stacey, Glyn; Kurtz, Andreas

    2016-01-01

    The human pluripotent stem cell registry (hPSCreg), accessible at http://hpscreg.eu, is a public registry and data portal for human embryonic and induced pluripotent stem cell lines (hESC and hiPSC). Since their first isolation the number of hESC lines has steadily increased to over 3000 and new iPSC lines are generated in a rapidly growing number of laboratories as a result of their potentially broad applicability in biomedicine and drug testing. Many of these lines are deposited in stem cell banks, which are globally established to store tens of thousands of lines from healthy and diseased donors. The Registry provides comprehensive and standardized biological and legal information as well as tools to search and compare information from multiple hPSC sources and hence addresses a translational research need. To facilitate unambiguous identification over different resources, hPSCreg automatically creates a unique standardized name for each cell line registered. In addition to biological information, hPSCreg stores extensive data about ethical standards regarding cell sourcing and conditions for application and privacy protection. hPSCreg is the first global registry that holds both, manually validated scientific and ethical information on hPSC lines, and provides access by means of a user-friendly, mobile-ready web application. PMID:26400179

  8. Microfluidic technology enhances the potential of human pluripotent stem cells.

    Science.gov (United States)

    Gagliano, Onelia; Elvassore, Nicola; Luni, Camilla

    2016-05-01

    Since the discovery of human somatic cell reprogramming, human induced pluripotent stem cells (hiPSC) have been increasingly recognized as the landmark for development of organs-on-chip. hiPSCs show a remarkable plasticity that is related to their ability to promptly respond to the surrounding environment. In vitro, the soluble culture microenvironment, with its critical balance between exogenous and cell-secreted factors, plays a great role in inducing hiPSC response, for both preserving pluripotency and controlling differentiation stages. Exploring the complexity of hiPSC microenvironment requires new experimental tools, as a tight control is limited within conventional culture dishes. Microfluidic technology is particularly attractive in hiPSC research because of its ability to mimic specific environmental cues by accurate control of soluble factors with high spatiotemporal resolution and in a high-throughput fashion. In this review, we highlight recent progress in hiPSC research enabled by microfluidic technology as well as new emerging scenarios. PMID:26772885

  9. Derivation, characterization and retinal differentiation of induced pluripotent stem cells

    Indian Academy of Sciences (India)

    Subba Rao Mekala; Vasundhara Vauhini; Usha Nagarajan; Savitri Maddileti; Subhash Gaddipati; Indumathi Mariappan

    2013-03-01

    Millions of people world over suffer visual disability due to retinal dystrophies which can be age-related or a genetic disorder resulting in gradual degeneration of the retinal pigmented epithelial (RPE) cells and photoreceptors. Therefore, cell replacement therapy offers a great promise in treating such diseases. Since the adult retina does not harbour any stem cells, alternative stem cell sources like the embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) offer a great promise for generating different cell types of the retina. Here, we report the derivation of four iPSC lines from mouse embryonic fibroblasts (MEFs) using a cocktail of recombinant retroviruses carrying the genes for Oct4, Sox2, Klf4 and cMyc. The iPS clone MEF-4F3 was further characterized for stemness marker expression and stable reprogramming by immunocytochemistry, FACS and RT-PCR analysis. Methylation analysis of the nanog promoter confirmed the reprogrammed epigenetic state. Pluripotency was confirmed by embryoid body (EB) formation and lineage-specific marker expression. Also, upon retinal differentiation, patches of pigmented cells with typical cobble-stone phenotype similar to RPE cells are generated within 6 weeks and they expressed ZO-1 (tight junction protein), RPE65 and bestrophin (mature RPE markers) and showed phagocytic activity by the uptake of fluorescent latex beads.

  10. Induced pluripotent stem cell lines derived from equine fibroblasts.

    Science.gov (United States)

    Nagy, Kristina; Sung, Hoon-Ki; Zhang, Puzheng; Laflamme, Simon; Vincent, Patrick; Agha-Mohammadi, Siamak; Woltjen, Knut; Monetti, Claudio; Michael, Iacovos Prodromos; Smith, Lawrence Charles; Nagy, Andras

    2011-09-01

    The domesticated horse represents substantial value for the related sports and recreational fields, and holds enormous potential as a model for a range of medical conditions commonly found in humans. Most notable of these are injuries to muscles, tendons, ligaments and joints. Induced pluripotent stem (iPS) cells have sparked tremendous hopes for future regenerative therapies of conditions that today are not possible to cure. Equine iPS (EiPS) cells, in addition to bringing promises to the veterinary field, open up the opportunity to utilize horses for the validation of stem cell based therapies before moving into the human clinical setting. In this study, we report the generation of iPS cells from equine fibroblasts using a piggyBac (PB) transposon-based method to deliver transgenes containing the reprogramming factors Oct4, Sox2, Klf4 and c-Myc, expressed in a temporally regulated fashion. The established iPS cell lines express hallmark pluripotency markers, display a stable karyotype even during long-term culture, and readily form complex teratomas containing all three embryonic germ layer derived tissues upon in vivo grafting into immunocompromised mice. Our EiPS cell lines hold the promise to enable the development of a whole new range of stem cell-based regenerative therapies in veterinary medicine, as well as aid the development of preclinical models for human applications. EiPS cell could also potentially be used to revive recently extinct or currently threatened equine species. PMID:21347602

  11. Induced pluripotent stem cells: from Nobel Prizes to clinical applications.

    Science.gov (United States)

    Rashid, S Tamir; Alexander, Graeme J M

    2013-03-01

    Advances in basic hepatology have been constrained for many years by the inability to culture primary hepatocytes in vitro, until just over five years ago when the scientific playing field was changed beyond recognition with the demonstration that human skin fibroblasts could be reprogrammed to resemble embryonic cells. The reprogrammed cells, known as induced pluripotent stem cells (iPSCs), were then shown to have the capacity to re-differentiate into almost any human cell type, including hepatocytes. The unlimited number and isogenic nature of the cells that can be generated from tiny fragments of tissue have massive implications for the study of human liver diseases in vitro. Of more immediate clinical importance were recent data demonstrating precision gene therapy on patient specific iPSCs, which opens up the real and exciting possibility of autologous hepatocyte transplantation as a substitute for allogeneic whole liver transplantation, which has been an effective approach to end-stage liver disease, but one that has now been outstripped by demand. In this review, we describe the historical development, current technology and potential clinical applications of induced pluripotency, concluding with a perspective on possible future directions in this dynamic field. PMID:23131523

  12. Use of human pluripotent stem cells to study and treatretinopathies

    Institute of Scientific and Technical Information of China (English)

    Karim Ben M’Barek; Florian Regent; Christelle Monville

    2015-01-01

    Human cell types affected by retinal diseases (such asage-related macular degeneration or retinitis pimentosa)are limited in cell number and of reduced accessibility. As aconsequence, their isolation for in vitro studies of diseasemechanisms or for drug screening efforts is fastidious.Human pluripotent stem cells (hPSCs), either of embryonicorigin or through reprogramming of adult somatic cells,represent a new promising way to generate models ofhuman retinopathies, explore the physiopathologicalmechanisms and develop novel therapeutic strategies.Disease-specific human embryonic stem cells were thefirst source of material to be used to study certain diseasestates. The recent demonstration that human somaticcells, such as fibroblasts or blood cells, can be geneticallyconverted to induce pluripotent stem cells together withthe continuous improvement of methods to differentiatethese cells into disease-affected cellular subtypes opensnew perspectives to model and understand a largenumber of human pathologies, including retinopathies.This review focuses on the added value of hPSCs for thedisease modeling of human retinopathies and the study oftheir molecular pathological mechanisms. We also discussthe recent use of these cells for establishing the validationstudies for therapeutic intervention and for the screeningof large compound libraries to identify candidate drugs.

  13. Induced Pluripotent Stem Cell Technology in Regenerative Medicine and Biology

    Science.gov (United States)

    Pei, Duanqing; Xu, Jianyong; Zhuang, Qiang; Tse, Hung-Fat; Esteban, Miguel A.

    The potential of human embryonic stem cells (ESCs) for regenerative medicine is unquestionable, but practical and ethical considerations have hampered clinical application and research. In an attempt to overcome these issues, the conversion of somatic cells into pluripotent stem cells similar to ESCs, commonly termed nuclear reprogramming, has been a top objective of contemporary biology. More than 40 years ago, King, Briggs, and Gurdon pioneered somatic cell nuclear reprogramming in frogs, and in 1981 Evans successfully isolated mouse ESCs. In 1997 Wilmut and collaborators produced the first cloned mammal using nuclear transfer, and then Thomson obtained human ESCs from in vitro fertilized blastocysts in 1998. Over the last 2 decades we have also seen remarkable findings regarding how ESC behavior is controlled, the importance of which should not be underestimated. This knowledge allowed the laboratory of Shinya Yamanaka to overcome brilliantly conceptual and technical barriers in 2006 and generate induced pluripotent stem cells (iPSCs) from mouse fibroblasts by overexpressing defined combinations of ESC-enriched transcription factors. Here, we discuss some important implications of human iPSCs for biology and medicine and also point to possible future directions.

  14. Induced Pluripotent Stem Cell Generation-Associated Point Mutations Arise during the Initial Stages of the Conversion of These Cells

    Directory of Open Access Journals (Sweden)

    Mayumi Sugiura

    2014-01-01

    Full Text Available A large number of point mutations have been identified in induced pluripotent stem cell (iPSC genomes to date. Whether these mutations are associated with iPSC generation is an important and controversial issue. In this study, we approached this critical issue in different ways, including an assessment of iPSCs versus embryonic stem cells (ESCs, and an investigation of variant allele frequencies and the heterogeneity of point mutations within a single iPSC clone. Through these analyses, we obtained strong evidence that iPSC-generation-associated point mutations occur frequently in a transversion-predominant manner just after the onset of cell lineage conversion. The heterogeneity of the point mutation profiles within an iPSC clone was also revealed and reflects the history of the emergence of each mutation. Further, our results suggest a possible approach for establishing iPSCs with fewer point mutations.

  15. Induced Pluripotent Stem Cell Generation-Associated Point Mutations Arise during the Initial Stages of the Conversion of These Cells

    Science.gov (United States)

    Sugiura, Mayumi; Kasama, Yasuji; Araki, Ryoko; Hoki, Yuko; Sunayama, Misato; Uda, Masahiro; Nakamura, Miki; Ando, Shunsuke; Abe, Masumi

    2014-01-01

    Summary A large number of point mutations have been identified in induced pluripotent stem cell (iPSC) genomes to date. Whether these mutations are associated with iPSC generation is an important and controversial issue. In this study, we approached this critical issue in different ways, including an assessment of iPSCs versus embryonic stem cells (ESCs), and an investigation of variant allele frequencies and the heterogeneity of point mutations within a single iPSC clone. Through these analyses, we obtained strong evidence that iPSC-generation-associated point mutations occur frequently in a transversion-predominant manner just after the onset of cell lineage conversion. The heterogeneity of the point mutation profiles within an iPSC clone was also revealed and reflects the history of the emergence of each mutation. Further, our results suggest a possible approach for establishing iPSCs with fewer point mutations. PMID:24511470

  16. Modular Architecture for the Measurement of Space Radiation

    Science.gov (United States)

    Delaune, Paul; Turner, Kathryn; Holland, S. Douglas; Carson, William R.; Riman, Fadi

    2007-01-01

    A modular architecture has been conceived for the design of radiation-monitoring instruments used aboard spacecraft and in planetary-exploration settings. This architecture reflects lessons learned from experience with prior radiation-monitoring instruments. A prototype instrument that embodies the architecture has been developed as part of the Mars Advanced Radiation Acquisition (MARA) project. The architecture is also applicable on Earth for radiation-monitoring instruments in research of energetic electrically charged particles and instruments monitoring radiation for purposes of safety, military defense, and detection of hidden nuclear devices and materials.

  17. Minimalist Architecture; Discussion of Its Sustainability in Indonesia

    Directory of Open Access Journals (Sweden)

    Silfia Mona Aryani

    2011-01-01

    Full Text Available Architecture develops along with particular society changing. In the period of modern, some traditional architecture with their complex rules become considered old fashioned. It was not implemented in modern buildings. When functionality becomes priority, minimalist architecture, recognized as Neo-Modernism, spreads and offers reflection of modern lifestyle. However, every style is not always suitable for each circumstance. The unconditional application of style can create another problem instead of a solution. This essay will discuss the existence of minimalism in architecture; its historical relationship with modernism, the theoretical reviews which underpin the discussion and the appropriate adaptations need to be made to fit in tropical climate.

  18. Derivation and transcriptional profiling analysis of pluripotent stem cell lines from rat blastocysts

    Institute of Scientific and Technical Information of China (English)

    Chunliang Li; Ying Yang; Junjie Gu; Yu Ma; Ying Jin

    2009-01-01

    Embryonic stem (ES) cells are derived from blastocyst-stage embryos. Their unique properties of self-renewal and pluripotency make them an attractive tool for basic research and a potential cell resource for therapy. ES cells of mouse and human have been successfully generated and applied in a wide range of research. However, no genuine ES cell lines have been obtained from rat to date. In this study, we identified pluripotent cells in early rat embryos using specific antibodies against markers of pluripotent stem cells. Subsequently, by modifying the culture medium for rat blastocysts, we derived pluripotent rat ES-llke cell lines, which expressed pluripotency markers and formed embryoid bodies (EBs) in vitro. Importantly, these rat ES-like cells were able to produce teratomas. Both EBs and teratomas contained tissues from all three embryonic germ layers, in addition, from the rat ES-like cells, we derived a rat primitive endoderm (PrE) cell line. Furthermore, we conducted transcriptional profiling of the rat ES-like cells and identified the unique molecular signature of the rat pluripotent stem cells. Our analysis demonstrates that multiple signaling pathways, including the BMP, Activin and roTOR pathways, may be involved in keeping the rat ES-like cells in an undifferentiated state. The cell lines and information obtained in this study will accelerate our understanding of the molecular regulation underlying pluripotency and guide us in the appropriate manipulation of ES cells from a particular species.

  19. Current protocols in the generation of pluripotent stem cells: theoretical, methodological and clinical considerations

    Directory of Open Access Journals (Sweden)

    Brad B Swelstad

    2009-12-01

    Full Text Available Brad B Swelstad, Candace L KerrInstitute for Cell Engineering, Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, MA, USAAbstract: Pluripotent stem cells have been derived from various embryonic, fetal and adult sources. Embryonic stem cells (ESCs and parthenogenic ESCs (pESCs are derived from the embryo proper while embryonic germ cells (EGCs, embryonal carcinoma cells (ECCs, and germ-line stem cells (GSC are produced from germ cells. ECCs were the first pluripotent stem cell lines established from adult testicular tumors while EGCs are generated in vitro from primordial germ cells (PGCs isolated in late embryonic development. More recently, studies have also demonstrated the ability to produce GSCs from adult germ cells, known as spermatogonial stem cells. Unlike ECCs, the source of GSCs are normal, non-cancerous adult tissue. The study of these unique cell lines has provided information that has led to the ability to reprogram somatic cells into an ESC-like state. These cells, called induced pluripotent stem cells (iPSCs, have been derived from a number of human fetal and adult origins. With the promises pluripotent stem cells bring to cell-based therapies there remain several considerations that need to be carefully studied prior to their clinical use. Many of these issues involve understanding key factors regulating their generation, including those which define pluripotency. In this regard, the following article discusses critical aspects of pluripotent stem cell derivation and current issues about their therapeutic potential.Keywords: pluripotency, stem cells, derivation, human

  20. Human pluripotent stem cell-derived neural constructs for predicting neural toxicity.

    Science.gov (United States)

    Schwartz, Michael P; Hou, Zhonggang; Propson, Nicholas E; Zhang, Jue; Engstrom, Collin J; Santos Costa, Vitor; Jiang, Peng; Nguyen, Bao Kim; Bolin, Jennifer M; Daly, William; Wang, Yu; Stewart, Ron; Page, C David; Murphy, William L; Thomson, James A

    2015-10-01

    Human pluripotent stem cell-based in vitro models that reflect human physiology have the potential to reduce the number of drug failures in clinical trials and offer a cost-effective approach for assessing chemical safety. Here, human embryonic stem (ES) cell-derived neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors were combined on chemically defined polyethylene glycol hydrogels and cultured in serum-free medium to model cellular interactions within the developing brain. The precursors self-assembled into 3D neural constructs with diverse neuronal and glial populations, interconnected vascular networks, and ramified microglia. Replicate constructs were reproducible by RNA sequencing (RNA-Seq) and expressed neurogenesis, vasculature development, and microglia genes. Linear support vector machines were used to construct a predictive model from RNA-Seq data for 240 neural constructs treated with 34 toxic and 26 nontoxic chemicals. The predictive model was evaluated using two standard hold-out testing methods: a nearly unbiased leave-one-out cross-validation for the 60 training compounds and an unbiased blinded trial using a single hold-out set of 10 additional chemicals. The linear support vector produced an estimate for future data of 0.91 in the cross-validation experiment and correctly classified 9 of 10 chemicals in the blinded trial. PMID:26392547

  1. Architecture and Stages

    DEFF Research Database (Denmark)

    Kiib, Hans

    2009-01-01

    future. But this is not enough. The agenda is to develop architectural spaces, where social interaction and learning are enhanced by art and fun. How can we develop new architectural designs in our inner cities and waterfronts where eventscapes, learning labs and temporal use are merged with everyday......Architecture and Art as Fuel New development zones for shopping and entertainment and space for festivals inside the city CAN be coupled with art and architecture and become ‘open minded' public domains based on cultural exchange and mutual learning. This type of space could be labelled as...... "experiencescape" - a space between tourism, culture, learning and economy. Strategies related to these challenges involve new architectural concepts and art as ‘engines' for a change. New expressive architecture and old industrial buildings are often combined into hybrid narratives, linking the past with the...

  2. Research on the Contemporary Japanese Architectural Creation and its Special Aesthetical Taste of Nationality

    Directory of Open Access Journals (Sweden)

    Shan Linlin

    2013-08-01

    Full Text Available Contemporary Japanese architecture has achieved great success and has been widely accepted by the whole architectural field. What is the driving force for the contemporary Japanese architectural creation is worth of thinking carefully about. In this study, some famous Japanese architects, including Toyo Ito, Tadao Ando, Arata Isozaki, Kengo Kuma, Kazuyo Sejima and Ryue Nishizawa and their architectural studiess are analyzed and studied from the angle of nationality. These architects keep up with the step of the world architecture and always pursuit the aesthetical taste of nationality. They proposed some special architectural theories that profoundly reflect the nationality of Japanese and make great influence on the architectural forms, architectural space and architectural aesthetics of Contemporary Japanese architecture. In the architectural form, they pursuit the simplicity, pureness, lightness and finesses; in the architectural space and behavior, they pursuit the shadow of the ma space and nature existence; in the architectural aesthetics, they pursuit the beauty of animism, dreariness and substance sadness. Through conjoint analysis of the architectural examples and the theory of nationality, this study proposed that the contemporary Japanese architectural creation is directly derived from the profound traditional culture and firm nationality and nationality is the cornerstone of the Japanese architecture and always promotes the progress of the Japanese architecture.

  3. Architecture humanitarian emergencies

    DEFF Research Database (Denmark)

    Gomez-Guillamon, Maria; Eskemose Andersen, Jørgen; Contreras, Jorge Lobos;

    2013-01-01

    Introduced by scientific articles conserning architecture and human rights in light of cultures, emergencies, social equality and sustainability, democracy, economy, artistic development and science into architecture. Concluding in definition of needs for new roles, processes and education of...... architecture. Followed by articles focusing on interdisciplinary research and design of emergency shelters as well as educational environments. Finally concretized in 35 studies from international workshops arranged globally on and by different architect schools: Royal Danish Academy of Fine Arts in Denmark...

  4. Discovery Food - Culinary Architecture

    OpenAIRE

    Buettner-Graefenhain, Christine

    2005-01-01

    What keeps places unique in times of globalization? If information, goods, food, architecture are the same everywhere, what`s the difference between places? What are people identifying with? Eating habits are a main factor of cultural identification. How can architecture contribute to these feelings of belonging, self awareness and joy? How can it teach something about the place and the people living there? What if a new kind of culinary architecture can help opening people`s e...

  5. An Architecture for Autonomy

    OpenAIRE

    Alami, Rachid; Chatila, Raja; Fleury, Sara; Ghallab, Malik; Ingrand, Félix

    1998-01-01

    International audience An autonomous robot offers a challenging and ideal field for the study of intelligent architectures. Autonomy within a rational behavior could be evaluated by the robot's effectiveness and robustness in carrying out tasks in different and ill-known environments_ It raises major requirements on the control architecture. Furthermore, a robot as a programmable machine brings up other architectural needs, such as the ease and quality of its speci_cation and programming. ...

  6. Architecture Criticism Blindfolded

    OpenAIRE

    Ann Heylighen; Jasmien Herssens; Hubert Froyen

    2009-01-01

    The paper reports on a recent Belgian initiative targeting architectural practice through the professional press. Architecture critics were invited to revisit an exemplary public building while being blindfolded and guided by persons who are visually impaired. Afterwards, they were asked to report on this visit in an article for an architectural magazine. The initiative aimed at drawing the attention of the critics—and, by extension, the readers of their articles—to the need for accessibil...

  7. Architecture of Network Systems

    CERN Document Server

    Serpanos, Dimitrios

    2011-01-01

    Network systems require technical skills in computer architecture, design methodologies, algorithm design, and networking. Architecture of Network Systems explains the practice and methodologies that will allow you to solve a broad range of problems in system design, including problems related to security, quality of service, performance, manageability, and more. Leading researchers Dimitrios Serpanos and Tilman Wolf develop architectures for all network sub-systems, bridging the gap between operation and VLSI. Discussing the major challenges in the design of networks and the architectures tha

  8. IT Architecture For Dummies

    CERN Document Server

    Hausman, Kalani Kirk

    2010-01-01

    A solid introduction to the practices, plans, and skills required for developing a smart system architecture. Information architecture combines IT skills with business skills in order to align the IT structure of an organization with the mission, goals, and objectives of its business. This friendly introduction to IT architecture walks you through the myriad issues and complex decisions that many organizations face when setting up IT systems to work in sync with business procedures. Veteran IT professional and author Kirk Hausman explains the business value behind IT architecture and provides

  9. Grid Architecture 2

    Energy Technology Data Exchange (ETDEWEB)

    Taft, Jeffrey D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-01-01

    The report describes work done on Grid Architecture under the auspices of the Department of Electricity Office of Electricity Delivery and Reliability in 2015. As described in the first Grid Architecture report, the primary purpose of this work is to provide stakeholder insight about grid issues so as to enable superior decision making on their part. Doing this requires the creation of various work products, including oft-times complex diagrams, analyses, and explanations. This report provides architectural insights into several important grid topics and also describes work done to advance the science of Grid Architecture as well.

  10. Evolution of gene regulation of pluripotency - the case for wiki tracks at genome browsers

    Directory of Open Access Journals (Sweden)

    Struckmann Stephan

    2010-12-01

    Full Text Available Abstract Background Experimentally validated data on gene regulation are hard to obtain. In particular, information about transcription factor binding sites in regulatory regions are scattered around in the literature. This impedes their systematic in-context analysis, e.g. the inference of their conservation in evolutionary history. Results We demonstrate the power of integrative bioinformatics by including curated transcription factor binding site information into the UCSC genome browser, using wiki and custom tracks, which enable easy publication of annotation data. Data integration allows to investigate the evolution of gene regulation of the pluripotency-associated genes Oct4, Sox2 and Nanog. For the first time, experimentally validated transcription factor binding sites in the regulatory regions of all three genes were assembled together based on manual curation of data from 39 publications. Using the UCSC genome browser, these data were then visualized in the context of multi-species conservation based on genomic alignment. We confirm previous hypotheses regarding the evolutionary age of specific regulatory patterns, establishing their "deep homology". We also confirm some other principles of Carroll's "Genetic theory of Morphological Evolution", such as "mosaic pleiotropy", exemplified by the dual role of Sox2 reflected in its regulatory region. Conclusions We were able to elucidate some aspects of the evolution of gene regulation for three genes associated with pluripotency. Based on the expected return on investment for the community, we encourage other scientists to contribute experimental data on gene regulation (original work as well as data collected for reviews to the UCSC system, to enable studies of the evolution of gene regulation on a large scale, and to report their findings. Reviewers This article was reviewed by Dr. Gustavo Glusman and Dr. Juan Caballero, Institute for Systems Biology, Seattle, USA (nominated by Dr. Doron

  11. miR-290/371-Mbd2-Myc circuit regulates glycolytic metabolism to promote pluripotency

    OpenAIRE

    Cao, Yang; Guo, Wen-Ting; Tian, Shengya; He, Xiaoping; Wang, Xi-Wen; Liu, Xiaomeng; Gu, Kai-Li; Ma, Xiaoyu; Huang,, X.T.; Hu, Lan; Cai, Yongping; Zhang, Huafeng; Wang, Yangming; Gao, Ping

    2015-01-01

    Enhanced glycolysis is a main feature of pluripotent stem cells (PSCs) and is proposed to be important for the maintenance and induction of pluripotency. The molecular mechanism underlying enhanced glycolysis in PSCs is not clear. Using Dgcr8−/− mouse embryonic stem cells (ESCs) that lack mature miRNAs, we found that miR-290 cluster of miRNAs stimulates glycolysis by upregulating glycolytic enzymes Pkm2 and Ldha, which are also essential for the induction of pluripotency during reprogramming....

  12. Assessment of porcine-induced pluripotent stem cells by in vivo assays

    DEFF Research Database (Denmark)

    Secher, Jan Ole Bertelsen; Freude, Karla Kristine; Petkov, Stoyan Gueorguiev;

    for mouse and rat iPSC. Acquiring insight into these caveats will greatly benefit the generation of bona fide piPSC lines. Here, we sought to examine these caveats through: 1) comprehensive characterization of the pluripotency state of piPSC-like cells and 2) comparative transcriptome analyses between......, we identify a unique gene expression profile indicating the missing links in regards to pluripotency factors and growth factor receptors. These will be incorporated in our future efforts to derive and maintain bona fide stable naïve pluripotent piPSC....

  13. Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective

    Institute of Scientific and Technical Information of China (English)

    Gaoyang Liang; Yi Zhang

    2013-01-01

    Pluripotent stem cells,like embryonic stem cells (ESCs),have specialized epigenetic landscapes,which are important for pluripotency maintenance.Transcription factor-mediated generation of induced pluripotent stem cells (iPSCs)requires global change of somatic cell epigenetic status into an ESC-like state.Accumulating evidence indicates that epigenetic mechanisms not only play important roles in the iPSC generation process,but also affect the properties of reprogrammed iPSCs.Understanding the roles of various epigenetic factors in iPSC generation contributes to our knowledge of the reprogramming mechanisms.

  14. Mga is essential for the survival of pluripotent cells during peri-implantation development

    OpenAIRE

    Washkowitz, Andrew J.; Schall, Caroline; Zhang, Kun; Wurst, Wolfgang; FLOSS, Thomas; Mager, Jesse; Papaioannou, Virginia E

    2015-01-01

    The maintenance and control of pluripotency is of great interest in stem cell biology. The dual specificity T-box/basic-helix-loop-helix-zipper transcription factor Mga is expressed in the pluripotent cells of the inner cell mass (ICM) and epiblast of the peri-implantation mouse embryo, but its function has not been investigated previously. Here, we use a loss-of-function allele and RNA knockdown to demonstrate that Mga depletion leads to the death of proliferating pluripotent ICM cells in vi...

  15. Pluripotent stem cell-derived neural stem cells: From basic research to applications

    Institute of Scientific and Technical Information of China (English)

    Masahiro; Otsu; Takashi; Nakayama; Nobuo; Inoue

    2014-01-01

    Basic research on pluripotent stem cells is designed to enhance understanding of embryogenesis, whereas applied research is designed to develop novel therapies and prevent diseases. Attainment of these goals has been enhanced by the establishment of embryonic stem cell lines, the technological development of genomic reprogramming to generate induced-pluripotent stem cells, and improvements in in vitro techniques to manipulate stem cells. This review summarizes the techniques required to generate neural cells from pluripotent stem cells. In particular, this review describes current research applications of a simple neural differentiation method, the neural stem sphere method, which we developed.

  16. Derivation and characterization of sleeping beauty transposon-mediated porcine induced pluripotent stem cells

    DEFF Research Database (Denmark)

    Kues, Wilfried A.; Herrmann, Doris; Barg-Kues, Brigitte;

    2013-01-01

    the nonviral Sleeping Beauty transposon system to deliver the reprogramming factors Oct4, Sox2, Klf4, and cMyc. Successful reprogramming to a pluripotent state was indicated by changes in cell morphology and reactivation of the Oct4-EGFP reporter. The transposon-reprogrammed induced pluripotent stem...... (iPS) cells showed long-term proliferation in vitro over >40 passages, expressed transcription factors typical of embryonic stem cells, including OCT4, NANOG, SOX2, REX1, ESRRB, DPPA5, and UTF1 and surface markers of pluripotency, including SSEA-1 and TRA-1-60. In vitro differentiation resulted in...

  17. Digitally-Driven Architecture

    Directory of Open Access Journals (Sweden)

    Henriette Bier

    2010-06-01

    Full Text Available The shift from mechanical to digital forces architects to reposition themselves: Architects generate digital information, which can be used not only in designing and fabricating building components but also in embedding behaviours into buildings. This implies that, similar to the way that industrial design and fabrication with its concepts of standardisation and serial production influenced modernist architecture, digital design and fabrication influences contemporary architecture. While standardisa­tion focused on processes of rationalisation of form, mass-customisation as a new paradigm that replaces mass-production, addresses non-standard, complex, and flexible designs. Furthermore, knowledge about the designed object can be encoded in digital data pertaining not just to the geometry of a design but also to its physical or other behaviours within an environment. Digitally-driven architecture implies, therefore, not only digitally-designed and fabricated architecture, it also implies architecture – built form – that can be controlled, actuated, and animated by digital means. In this context, this sixth Footprint issue examines the influence of digital means as prag­matic and conceptual instruments for actuating architecture. The focus is not so much on computer-based systems for the development of architectural designs, but on architecture incorporating digital control, sens­ing, actuating, or other mechanisms that enable buildings to inter­act with their users and surroundings in real time in the real world through physical or sensory change and variation.

  18. Digitally-Driven Architecture

    Directory of Open Access Journals (Sweden)

    Henriette Bier

    2014-07-01

    Full Text Available The shift from mechanical to digital forces architects to reposition themselves: Architects generate digital information, which can be used not only in designing and fabricating building components but also in embedding behaviours into buildings. This implies that, similar to the way that industrial design and fabrication with its concepts of standardisation and serial production influenced modernist architecture, digital design and fabrication influences contemporary architecture. While standardisation focused on processes of rationalisation of form, mass-customisation as a new paradigm that replaces mass-production, addresses non-standard, complex, and flexible designs. Furthermore, knowledge about the designed object can be encoded in digital data pertaining not just to the geometry of a design but also to its physical or other behaviours within an environment. Digitally-driven architecture implies, therefore, not only digitally-designed and fabricated architecture, it also implies architecture – built form – that can be controlled, actuated, and animated by digital means.In this context, this sixth Footprint issue examines the influence of digital means as pragmatic and conceptual instruments for actuating architecture. The focus is not so much on computer-based systems for the development of architectural designs, but on architecture incorporating digital control, sens­ing, actuating, or other mechanisms that enable buildings to inter­act with their users and surroundings in real time in the real world through physical or sensory change and variation.

  19. Clinical document architecture.

    Science.gov (United States)

    Heitmann, Kai

    2003-01-01

    The Clinical Document Architecture (CDA), a standard developed by the Health Level Seven organisation (HL7), is an ANSI approved document architecture for exchange of clinical information using XML. A CDA document is comprised of a header with associated vocabularies and a body containing the structural clinical information. PMID:15061557

  20. Software Architecture Evolution

    Science.gov (United States)

    Barnes, Jeffrey M.

    2013-01-01

    Many software systems eventually undergo changes to their basic architectural structure. Such changes may be prompted by new feature requests, new quality attribute requirements, changing technology, or other reasons. Whatever the causes, architecture evolution is commonplace in real-world software projects. Today's software architects, however,…

  1. Towards a Media Architecture

    DEFF Research Database (Denmark)

    Ebsen, Tobias

    2010-01-01

    This text explores the concept of media architecture as a phenomenon of visual culture that describes the use of screen-technology in new spatial configurations in practices of architecture and art. I shall argue that this phenomenon is not necessarily a revolutionary new approach, but rather...

  2. Workflow automation architecture standard

    Energy Technology Data Exchange (ETDEWEB)

    Moshofsky, R.P.; Rohen, W.T. [Boeing Computer Services Co., Richland, WA (United States)

    1994-11-14

    This document presents an architectural standard for application of workflow automation technology. The standard includes a functional architecture, process for developing an automated workflow system for a work group, functional and collateral specifications for workflow automation, and results of a proof of concept prototype.

  3. Architecture or Sculpture?

    DEFF Research Database (Denmark)

    Baumeister, Ruth

    Jørn Utzon´s museum design for Asger Jorn´s collection in Silkeborg contextualized in the postwar context of an organic architecture.......Jørn Utzon´s museum design for Asger Jorn´s collection in Silkeborg contextualized in the postwar context of an organic architecture....

  4. Architecture and energy

    DEFF Research Database (Denmark)

    Marsh, Rob; Lauring, Michael

    2011-01-01

    Traditional low-energy architecture has not necessarily led to reduced energy consumption. A paradigm shift is proposed promoting pluralistic energy-saving strategies.......Traditional low-energy architecture has not necessarily led to reduced energy consumption. A paradigm shift is proposed promoting pluralistic energy-saving strategies....

  5. Defined three-dimensional microenvironments boost induction of pluripotency

    Science.gov (United States)

    Caiazzo, Massimiliano; Okawa, Yuya; Ranga, Adrian; Piersigilli, Alessandra; Tabata, Yoji; Lutolf, Matthias P.

    2016-03-01

    Since the discovery of induced pluripotent stem cells (iPSCs), numerous approaches have been explored to improve the original protocol, which is based on a two-dimensional (2D) cell-culture system. Surprisingly, nothing is known about the effect of a more biologically faithful 3D environment on somatic-cell reprogramming. Here, we report a systematic analysis of how reprogramming of somatic cells occurs within engineered 3D extracellular matrices. By modulating microenvironmental stiffness, degradability and biochemical composition, we have identified a previously unknown role for biophysical effectors in the promotion of iPSC generation. We find that the physical cell confinement imposed by the 3D microenvironment boosts reprogramming through an accelerated mesenchymal-to-epithelial transition and increased epigenetic remodelling. We conclude that 3D microenvironmental signals act synergistically with reprogramming transcription factors to increase somatic plasticity.

  6. A Method for Genome Editing in Human Pluripotent Stem Cells.

    Science.gov (United States)

    Smith, Cory; Ye, Zhaohui; Cheng, Linzhao

    2016-01-01

    Human pluripotent stem cells (PSCs) hold great potential for regenerative medicine and currently are being used as a research tool for basic discovery and disease modeling. To evaluate the role of a single genetic variant, a system of genome editing is needed to precisely mutate any desired DNA sequence in isolation and measure its effect on phenotype when compared to the isogenic parental PSC from which it was derived. This protocol describes the general targeting schemes used by researchers to edit PSCs to knock out, knock-in, or precisely alter a single nucleotide, covering conditions for electroporation, clonal isolation, and screening of edited PSCs for the targeted mutation. These recent advances simplify the procedure for genome editing, allowing individual researchers to induce nearly any desired mutation to further study its function or to reverse a disease-causing variant for future applications in regenerative medicine. PMID:27037073

  7. Using human pluripotent stem cells to study Friedreich ataxia cardiomyopathy.

    Science.gov (United States)

    Crombie, Duncan E; Pera, Martin F; Delatycki, Martin B; Pébay, Alice

    2016-06-01

    Friedreich ataxia (FRDA) is the most common of the inherited ataxias. It is an autosomal recessive disease characterised by degeneration of peripheral sensory neurons, regions of the central nervous system and cardiomyopathy. FRDA is usually due to homozygosity for trinucleotide GAA repeat expansions found within first intron of the FRATAXIN (FXN) gene, which results in reduced levels of the mitochondrial protein FXN. Reduced FXN protein results in mitochondrial dysfunction and iron accumulation leading to increased oxidative stress and cell death in the nervous system and heart. Yet the precise functions of FXN and the underlying mechanisms leading to disease pathology remain elusive. This is particularly true of the cardiac aspect of FRDA, which remains largely uncharacterized at the cellular level. Here, we summarise current knowledge on experimental models in which to study FRDA cardiomyopathy, with a particular focus on the use of human pluripotent stem cells as a disease model. PMID:27019046

  8. Autophagic response to cell culture stress in pluripotent stem cells.

    Science.gov (United States)

    Gregory, Siân; Swamy, Sushma; Hewitt, Zoe; Wood, Andrew; Weightman, Richard; Moore, Harry

    2016-05-01

    Autophagy is an important conserved cellular process, both constitutively as a recycling pathway for long lived proteins and as an upregulated stress response. Recent findings suggest a fundamental role for autophagic processes in the maintenance of pluripotent stem cell function. In human embryonic stem cells (hESCS), autophagy was investigated by transfection of LC3-GFP to visualize autophagosomes and with an antibody to LC3B protein. The presence of the primary cilium (PC) in hESCs as the site of recruitment of autophagy-related proteins was also assessed. HESCs (mShef11) in vitro displayed basal autophagy which was upregulated in response to deprivation of culture medium replacement. Significantly higher levels of autophagy were exhibited on spontaneous differentiation of hESCs in vitro. The PC was confirmed to be present in hESCs and therefore may serve to coordinate autophagy function. PMID:26385182

  9. Utilizing FUCCI reporters to understand pluripotent stem cell biology.

    Science.gov (United States)

    Singh, Amar M; Trost, Robert; Boward, Benjamin; Dalton, Stephen

    2016-05-15

    The fluorescence ubiquitination cell cycle indicator (FUCCI) system provides a powerful method to evaluate cell cycle mechanisms associated with stem cell self-renewal and cell fate specification. By integrating the FUCCI system into human pluripotent stem cells (hPSCs) it is possible to isolate homogeneous fractions of viable cells representative of all cell cycle phases. This method avoids problems associated with traditional tools used for cell cycle analysis such as synchronizing drugs, elutriation and temperature sensitive mutants. Importantly, FUCCI reporters allow cell cycle events in dynamic systems, such as differentiation, to be evaluated. Initial reports on the FUCCI system focused on its strengths in reporting spatio-temporal aspects of cell cycle events in living cells and developmental models. In this report, we describe approaches that broaden the application of FUCCI reporters in PSCs through incorporation of FACS. This approach allows molecular analysis of the cell cycle in stem cell systems that were not previously possible. PMID:26404921

  10. KAJIAN INDUCED PLURIPOTENT STEMCELL (iPS (HARAPAN DAN TANTANGAN

    Directory of Open Access Journals (Sweden)

    Masagus Zainuri

    2014-05-01

    Full Text Available AbstractInduced Pluripotent Stemcell (iPS are adult cells which the genetic information in the nucleus of those cells being reprogrammed (reprogram by inserting exogenous pluripotential genes. The exogenous gene transduction is using vectors, such as lentivirus, retrovirus, or adenovirus, which suppressed the gene expression of the original cells, so they will express the transduced exogenous gene. Viral vectors are then used to reprogramming and producing iPS clones that are pluripotent. iPS derived from adult cells of patient with certain diseases will be used as a tool to study the mechanisms of those specific diseases and the effects of selected drugs against the diseases. Several previous studies have shown that iPS clones developed from specific genetic disease have its original genotype and retain the character of the response to the drug that similar as the original adult cells. Opportunities for the utilization of autologous iPS cell therapy in the future is wide open as expected iPS transplant will not be rejected when transplanted back to the patient. Behind all its potential, iPS production is still facing some problems to be applicable clinically. The use of viruses as vectors may cause problems due to virus gene sequences may be integrated into the genome of the DNA donor cell, thereby causing mutations of the iPS clones. Several subsequent studies have succeeded in replacing the use of viruses as vectors, but the level of efficiency obtained is still very low. Another problem that arises is that epigenetic changes may occur in iPS cultures. Many advanced research related to iPS may be developed in Indonesia and is necessary to improve the production efficiency of iPS and solve iPS clones epigenetic changes problems in the future.Keywords: iPS, pluripotency, transduction, transfection.AbstrakInduced Pluripotent Stemcell (iPS adalah sel somatic dewasa yang informasi genetika dalam inti selnyadiprogram ulang (reprogram dengan cara

  11. Pluripotent stem cells in disease modelling and drug discovery.

    Science.gov (United States)

    Avior, Yishai; Sagi, Ido; Benvenisty, Nissim

    2016-03-01

    Experimental modelling of human disorders enables the definition of the cellular and molecular mechanisms underlying diseases and the development of therapies for treating them. The availability of human pluripotent stem cells (PSCs), which are capable of self-renewal and have the potential to differentiate into virtually any cell type, can now help to overcome the limitations of animal models for certain disorders. The ability to model human diseases using cultured PSCs has revolutionized the ways in which we study monogenic, complex and epigenetic disorders, as well as early- and late-onset diseases. Several strategies are used to generate such disease models using either embryonic stem cells (ES cells) or patient-specific induced PSCs (iPSCs), creating new possibilities for the establishment of models and their use in drug screening. PMID:26818440

  12. A catalog of architectural primitives for modeling architectural patterns

    NARCIS (Netherlands)

    Zdun, Uwe; Avgeriou, Paris

    2008-01-01

    Architectural patterns are a fundamental aspect of the architecting process and subsequently the architectural documentation. Unfortunately, there is only poor support for modeling architectural patterns for two reasons. First, patterns describe recurring design solutions and hence do not directly m

  13. Product Architecture Modularity Strategies

    DEFF Research Database (Denmark)

    Mikkola, Juliana Hsuan

    2003-01-01

    The focus of this paper is to integrate various perspectives on product architecture modularity into a general framework, and also to propose a way to measure the degree of modularization embedded in product architectures. Various trade-offs between modular and integral product architectures and...... how components and interfaces influence the degree of modularization are considered. In order to gain a better understanding of product architecture modularity as a strategy, a theoretical framework and propositions are drawn from various academic literature sources. Based on the literature review......, the following key elements of product architecture are identified: components (standard and new-to-the-firm), interfaces (standardization and specification), degree of coupling, and substitutability. A mathematical function, termed modularization function, is introduced to measure the degree of...

  14. Induced pluripotent stem cells: Challenges and opportunities for cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Patty eSachamitr

    2014-04-01

    Full Text Available Despite recent advances in cancer treatment over the past 30 years, therapeutic options remain limited and do not always offer a cure for malignancy. Given that tumour associated antigens (TAA are, by definition, self-proteins, the need to productively engage autoreactive T cells remains at the heart of strategies for cancer immunotherapy. These have traditionally focussed on the administration of autologous monocyte-derived dendritic cells (moDC pulsed with TAA, or the ex vivo expansion and adoptive transfer of tumour infiltrating lymphocytes (TIL as a source of TAA-specific cytotoxic T cells (CTL. Although such approaches have shown some efficacy, success has been limited by the poor capacity of moDC to cross-present exogenous TAA to the CD8+ T cell repertoire and the potential for exhaustion of CTL expanded ex vivo. Recent advances in induced pluripotency offer opportunities to generate patient-specific stem cell lines with the potential to differentiate in vitro into cell types whose properties may help address these issues. Here we review recent success in the differentiation of NK cells from human induced pluripotent stem (iPS cells as well as minor subsets of DC with therapeutic potential, including CD141+XCR1+ DC, capable of cross-presenting TAA to naïve CD8+ T cells. Furthermore, we review recent progress in the use of TIL as the starting material for the derivation of iPSC lines, thereby capturing their antigen specificity in a self-renewing stem cell line, from which potentially unlimited numbers of naïve TAA-specific T cells may be differentiated, free of the risks of exhaustion.

  15. Prion protein expression regulates embryonic stem cell pluripotency and differentiation.

    Directory of Open Access Journals (Sweden)

    Alberto Miranda

    Full Text Available Cellular prion protein (PRNP is a glycoprotein involved in the pathogenesis of transmissible spongiform encephalopathies (TSEs. Although the physiological function of PRNP is largely unknown, its key role in prion infection has been extensively documented. This study examines the functionality of PRNP during the course of embryoid body (EB differentiation in mouse Prnp-null (KO and WT embryonic stem cell (ESC lines. The first feature observed was a new population of EBs that only appeared in the KO line after 5 days of differentiation. These EBs were characterized by their expression of several primordial germ cell (PGC markers until Day 13. In a comparative mRNA expression analysis of genes playing an important developmental role during ESC differentiation to EBs, Prnp was found to participate in the transcription of a key pluripotency marker such as Nanog. A clear switching off of this gene on Day 5 was observed in the KO line as opposed to the WT line, in which maximum Prnp and Nanog mRNA levels appeared at this time. Using a specific antibody against PRNP to block PRNP pathways, reduced Nanog expression was confirmed in the WT line. In addition, antibody-mediated inhibition of ITGB5 (integrin αvβ5 in the KO line rescued the low expression of Nanog on Day 5, suggesting the regulation of Nanog transcription by Prnp via this Itgb5. mRNA expression analysis of the PRNP-related proteins PRND (Doppel and SPRN (Shadoo, whose PRNP function is known to be redundant, revealed their incapacity to compensate for the absence of PRNP during early ESC differentiation. Our findings provide strong evidence for a relationship between Prnp and several key pluripotency genes and attribute Prnp a crucial role in regulating self-renewal/differentiation status of ESC, confirming the participation of PRNP during early embryogenesis.

  16. Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass.

    Science.gov (United States)

    Guo, Ge; von Meyenn, Ferdinand; Santos, Fatima; Chen, Yaoyao; Reik, Wolf; Bertone, Paul; Smith, Austin; Nichols, Jennifer

    2016-04-12

    Conventional generation of stem cells from human blastocysts produces a developmentally advanced, or primed, stage of pluripotency. In vitro resetting to a more naive phenotype has been reported. However, whether the reset culture conditions of selective kinase inhibition can enable capture of naive epiblast cells directly from the embryo has not been determined. Here, we show that in these specific conditions individual inner cell mass cells grow into colonies that may then be expanded over multiple passages while retaining a diploid karyotype and naive properties. The cells express hallmark naive pluripotency factors and additionally display features of mitochondrial respiration, global gene expression, and genome-wide hypomethylation distinct from primed cells. They transition through primed pluripotency into somatic lineage differentiation. Collectively these attributes suggest classification as human naive embryonic stem cells. Human counterparts of canonical mouse embryonic stem cells would argue for conservation in the phased progression of pluripotency in mammals. PMID:26947977

  17. Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass

    Directory of Open Access Journals (Sweden)

    Ge Guo

    2016-04-01

    Full Text Available Conventional generation of stem cells from human blastocysts produces a developmentally advanced, or primed, stage of pluripotency. In vitro resetting to a more naive phenotype has been reported. However, whether the reset culture conditions of selective kinase inhibition can enable capture of naive epiblast cells directly from the embryo has not been determined. Here, we show that in these specific conditions individual inner cell mass cells grow into colonies that may then be expanded over multiple passages while retaining a diploid karyotype and naive properties. The cells express hallmark naive pluripotency factors and additionally display features of mitochondrial respiration, global gene expression, and genome-wide hypomethylation distinct from primed cells. They transition through primed pluripotency into somatic lineage differentiation. Collectively these attributes suggest classification as human naive embryonic stem cells. Human counterparts of canonical mouse embryonic stem cells would argue for conservation in the phased progression of pluripotency in mammals.

  18. Young at Heart: Pioneering Approaches to Model Nonischaemic Cardiomyopathy with Induced Pluripotent Stem Cells

    Science.gov (United States)

    Gowran, Aoife; Rasponi, Marco; Perrucci, Gianluca L.; Righetti, Stefano; Zanobini, Marco; Pompilio, Giulio

    2016-01-01

    A mere 9 years have passed since the revolutionary report describing the derivation of induced pluripotent stem cells from human fibroblasts and the first in-patient translational use of cells obtained from these stem cells has already been achieved. From the perspectives of clinicians and researchers alike, the promise of induced pluripotent stem cells is alluring if somewhat beguiling. It is now evident that this technology is nascent and many areas for refinement have been identified and need to be considered before induced pluripotent stem cells can be routinely used to stratify, treat and cure patients, and to faithfully model diseases for drug screening purposes. This review specifically addresses the pioneering approaches to improve induced pluripotent stem cell based models of nonischaemic cardiomyopathy. PMID:27110250

  19. Inference of Transcriptional Network for Pluripotency in Mouse Embryonic Stem Cells

    International Nuclear Information System (INIS)

    In embryonic stem cells, various transcription factors (TFs) maintain pluripotency. To gain insights into the regulatory system controlling pluripotency, I inferred the regulatory relationships between the TFs expressed in ES cells. In this study, I applied a method based on structural equation modeling (SEM), combined with factor analysis, to 649 expression profiles of 19 TF genes measured in mouse Embryonic Stem Cells (ESCs). The factor analysis identified 19 TF genes that were regulated by several unmeasured factors. Since the known cell reprogramming TF genes (Pou5f1, Sox2 and Nanog) are regulated by different factors, each estimated factor is considered to be an input for signal transduction to control pluripotency in mouse ESCs. In the inferred network model, TF proteins were also arranged as unmeasured factors that control other TFs. The interpretation of the inferred network model revealed the regulatory mechanism for controlling pluripotency in ES cells

  20. Inspiring Reflections

    DEFF Research Database (Denmark)

    Muchie, Mammo

    2011-01-01

    life is not free from fluctuations, cycles, disruptions, crises and destructions both human and ecological. Innovation research ought to position itself to address environmental, financial and economic crises. The third is innovation research for development by addressing not only poverty erdaication......A numberof Chris Freeman's colleagues were asked to reflect on what they thought describes his life and work in a few words. Some of the colleagues replied including former SPRU students that were taught or supervised by Chris Freeman. Their views on what they thought were Chris Freeman's defining...... contributions have been put together. There are a number of ways to continue Chris Freeman's legacy on innovation research. The first is to build in a critical tradition in the economics of innovation research by introducing fearlessly emancipatory epistemology. Second the economic system that dominates social...

  1. ARCHITECTURE IN THE ISLAMIC CIVILIZATION: MUSLIM BUILDING OR ISLAMIC ARCHITECTURE

    OpenAIRE

    Ayat Ali Yassin; Dr. Nangkula Utaberta

    2012-01-01

    The main problem of the theory in the arena of islamic architecture is affected by some of its Westernthoughts, and stereotyping the islamic architecture according to Western thoughts; this leads to the breakdownof the foundations in the islamic architecture. It is a myth that islamic architecture is subjected to theinfluence from foreign architectures. This paper will highlight the dialectical concept of islamic architecture ormuslim buildings and the areas of recognition in islamic architec...

  2. Analysis of Architecture Pattern Usage in Legacy System Architecture Documentation

    OpenAIRE

    Harrison, Neil B.; Avgeriou, Paris

    2008-01-01

    Architecture patterns are an important tool in architectural design. However, while many architecture patterns have been identified, there is little in-depth understanding of their actual use in software architectures. For instance, there is no overview of how many patterns are used per system or which patterns are the most common or most important for particular domains. In addition, little is known of how architecture patterns may interact with each other. We studied architecture documentat...

  3. Lectin binding profiles of SSEA-4 enriched, pluripotent human embryonic stem cell surfaces

    OpenAIRE

    Shin Soojung; Jones Karen; Lyons Ian; Mitalipova Maisam; Venable Alison; Pierce Michael; Stice Steven

    2005-01-01

    Abstract Background Pluripotent human embryonic stem cells (hESCs) have the potential to form every cell type in the body. These cells must be appropriately characterized prior to differentiation studies or when defining characteristics of the pluripotent state. Some developmentally regulated cell surface antigens identified by monoclonal antibodies in a variety of species and stem cell types have proven to be side chains of membrane glycolipids and glycoproteins. Therefore, to examine hESC s...

  4. Transient Acquisition of Pluripotency During Somatic Cell Transdifferentiation with iPSC Reprogramming Factors

    OpenAIRE

    Maza, Itay; Caspi, Inbal; Zviran, Asaf; Chomsky, Elad; Rais, Yoach; Viukov, Sergey; Geula, Shay; Buenrostro, Jason D.; Weinberger, Leehee; Krupalnik, Vladislav; Hanna, Suhair; Zerbib, Mirie; Dutton, James R.; Greenleaf, William J.; Massarwa, Rada

    2015-01-01

    Somatic cells can be transdifferentiated to other cell types without passing through a pluripotent state by ectopic expression of appropriate transcription factors 1,2 . Recent reports have proposed an alternative transdifferentiation method in which fibroblasts are directly converted to various mature somatic cell types by brief expression of the induced pluripotent stem cell (iPSC) reprogramming factors Oct4, Sox2, Klf4 and c-Myc (OSKM) followed by cell expansion in media that promote linea...

  5. Derivation of Insulin-Producing Beta-Cells from Human Pluripotent Stem Cells

    OpenAIRE

    Schiesser, Jacqueline V.; Micallef, Suzanne J.; Hawes, Susan; Elefanty, Andrew G.; Stanley, Edouard G.

    2014-01-01

    Human embryonic stem cells have been advanced as a source of insulin-producing cells that could potentially replace cadaveric-derived islets in the treatment of type 1 diabetes. To this end, protocols have been developed that promote the formation of pancreatic progenitors and endocrine cells from human pluripotent stem cells, encompassing both embryonic stem cells and induced pluripotent stem cells. In this review, we examine these methods and place them in the context of the developmental a...

  6. Differentiate or Die: 3-Bromopyruvate and Pluripotency in Mouse Embryonic Stem Cells

    OpenAIRE

    Ana Sofia Rodrigues; Pereira, Sandro L.; Marcelo Correia; Andreia Gomes; Tânia Perestrelo; João Ramalho-Santos

    2015-01-01

    Background Pluripotent embryonic stem cells grown under standard conditions (ESC) have a markedly glycolytic profile, which is shared with many different types of cancer cells. Thus, some therapeutic strategies suggest that pharmacologically shifting cancer cells towards an oxidative phenotype, using glycolysis inhibitors, may reduce cancer aggressiveness. Given the metabolic parallels between cancer and stemness would chemotherapeutical agents have an effect on pluripotency, and could a stra...

  7. Induced pluripotent stem cells, new tools for drug discovery and new hope for stem cell therapies

    OpenAIRE

    Shi, Yanhong

    2009-01-01

    Somatic cell nuclear transfer or therapeutic cloning has provided great hope for stem cell-based therapies. However therapeutic cloning has been experiencing both ethical and technical difficulties. Recent breakthrough studies using a combination of four factors to reprogram human somatic cells into pluripotent stem cells without using embryos or eggs led to an important revolution in stem cell research. Comparative analysis of human induced pluripotent stem cells and human embryonic stem cel...

  8. Present state and future perspectives of using pluripotent stem cells in toxicology research

    OpenAIRE

    Wobus, Anna M.; Löser, Peter

    2011-01-01

    The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, a...

  9. Induced pluripotent stem cells: the long-expected revolution in medical science and practice?

    OpenAIRE

    Antonio Sorrentino

    2010-01-01

    Within the matter of a few years, development of the somatic reprogramming technology to generate induced pluripotent stem (iPS) cells has contributed enormously to the stem cell research field. We learned that differentiated adult cells possess an unrestricted plasticity that allows them to be driven back to their embryonic or pluripotent state, but owing to the juvenile nature of this novel science chapter, there are many unanswered questions and dilemmas. It is indisputable, however, that ...

  10. Engineering Adolescence: Maturation of Human Pluripotent Stem Cell-derived Cardiomyocytes

    OpenAIRE

    Yang, Xiulan; Pabon, Lil; Murry, Charles E.

    2014-01-01

    The discovery of human pluripotent stem cells (hPSCs), including both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), has opened up novel paths for a wide range of scientific studies. The capability to direct the differentiation of hPSCs into functional cardiomyocytes has provided a platform for regenerative medicine, development, tissue engineering, disease modeling, and drug toxicity testing. Despite exciting progress, achieving the optimal benefits has...

  11. Cardiomyocytes derived from human embryonic and induced pluripotent stem cells: comparative ultrastructure

    OpenAIRE

    Gherghiceanu, Mihaela; Barad, Lili; Novak, Atara; Reiter, Irina; Itskovitz-Eldor, Joseph; Binah, Ofer; Popescu, LM

    2011-01-01

    Abstract Induced pluripotent stem cells (iPSC) are generated from fully differentiated somatic cells that were reprogrammed into a pluripotent state. Human iPSC which can be obtained from various types of somatic cells such as fibroblasts or keratinocytes can differentiate into cardiomyocytes (iPSC-CM), which exhibit cardiac-like transmembrane action potentials, intracellular Ca2+ transients and contractions. While major features of the excitation-contraction coupling of iPSC-CM have been wel...

  12. Generation of induced pluripotent stem cells from human mesenchymal stem cells of parotid gland origin

    OpenAIRE

    Yan, Xing; Xu, Nuo; Meng, Cen; Wang, Bianhong; Yuan, Jinghong; Wang, Caiyun; Li, Yang

    2016-01-01

    The technology to reprogram human somatic cells to pluripotent state allows the generation of patient-specific induced pluripotent stem cells (iPSCs) and holds a great promise for regenerative medicine and autologous transplantation. Here we, for the first time, identified mesenchymal stem cells isolated from parotid gland (hPMSCs) as a suitable candidate for iPSC production. In the present study, hPMSCs were isolated from parotid gland specimens in patients with squamous cell carcinoma of th...

  13. Reprogramming human amniotic fluid stem cells to functional pluripotency by manipulation of culture conditions.

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Dafni Moschidou & Pascale V Guillot ### Abstract Pluripotent stem cells have potential applications in regenerative medicine, disease modelling and drug screening. Induced pluripotent stem (iPS) cells have first been generated from fibroblasts using retroviral insertion of OCT4A, SOX2, c-MYC and KLF4. Since then, a number of methods have been developed to avoid the random integration of ectopic factors in the genome and the low efficiency of the process. Those include alt...

  14. In vivo reprogrammed pluripotent stem cells from teratomas share analogous properties with their in vitro counterparts

    OpenAIRE

    Hyun Woo Choi; Jong Soo Kim; Yean Ju Hong; Hyuk Song; Han Geuk Seo; Jeong Tae Do

    2015-01-01

    Recently, induced pluripotent stem cells (iPSCs) have been generated in vivo from reprogrammable mice. These in vivo iPSCs display features of totipotency, i.e., they differentiate into the trophoblast lineage, as well as all 3 germ layers. Here, we developed a new reprogrammable mouse model carrying an Oct4-GFP reporter gene to facilitate the detection of reprogrammed pluripotent stem cells. Without doxycycline administration, some of the reprogrammable mice developed aggressively growing te...

  15. Successful disease-specific induced pluripotent stem cell generation from patients with kidney transplantation

    OpenAIRE

    Thatava, Tayaramma; Armstrong, Adam S.; De Lamo, Josep Genebriera; Edukulla, Ramakrishna; Khan, Yulia Krotova; Sakuma, Toshie; Ohmine, Seiga; Sundsbak, Jamie L; Harris, Peter C.; Kudva, Yogish C.; Ikeda, Yasuhiro

    2011-01-01

    Introduction End-stage renal disease (ESRD) is a major public health problem. Although kidney transplantation is a viable therapeutic option, this therapy is associated with significant limitations, including a shortage of donor organs. Induced pluripotent stem (iPS) cell technology, which allows derivation of patient-specific pluripotent stem cells, could provide a possible alternative modality for kidney replacement therapy for patients with ESRD. Methods The feasibility of iPS cell generat...

  16. Surface-engineered substrates for improved human pluripotent stem cell culture under fully defined conditions

    OpenAIRE

    Saha, Krishanu; Mei, Ying; Reisterer, Colin M.; Pyzocha, Neena Kenton; Yang, Jing; Muffat, Julien; Davies, Martyn C.; Alexander, Morgan R.; Langer, Robert; Anderson, Daniel G.; Jaenisch, Rudolf

    2011-01-01

    The current gold standard for the culture of human pluripotent stem cells requires the use of a feeder layer of cells. Here, we develop a spatially defined culture system based on UV/ozone radiation modification of typical cell culture plastics to define a favorable surface environment for human pluripotent stem cell culture. Chemical and geometrical optimization of the surfaces enables control of early cell aggregation from fully dissociated cells, as predicted from a numerical model of cell...

  17. Study of Pluripotency Markers in Zebrafish Embryos and Transient Embryonic Stem Cell Cultures

    OpenAIRE

    Robles, Vanesa; Martí, Mercé; Belmonte, Juan Carlos Izpisua

    2011-01-01

    Targeted genomic manipulation using embryonic stem (ES) cells has not yet been achieved in zebrafish, although methods for zebrafish ES cell culture has been described in literature. The knowledge of pluripotency markers in this species is almost nonexistent and this is a very limiting factor in the definition of the ideal culture conditions for ES cells. Here, we studied the expression of several genes associated with pluripotency in zebrafish embryonic cells versus differentiated cells and ...

  18. Architecture in the Experience City

    DEFF Research Database (Denmark)

    Kiib, Hans

    narratives related to historical buildings and architectural heritage; another group tries to embed new performative technologies in expressive architectural representation. The article provides a theoretical framework for the analysis of the political rationales of these projects and for the architectural...

  19. A highly efficient method for generation of therapeutic quality human pluripotent stem cells by using naive induced pluripotent stem cells nucleus for nuclear transfer.

    Science.gov (United States)

    Sanal, Madhusudana Girija

    2014-01-01

    Even after several years since the discovery of human embryonic stem cells and induced pluripotent stem cells (iPSC), we are still unable to make any significant therapeutic benefits out of them such as cell therapy or generation of organs for transplantation. Recent success in somatic cell nuclear transfer (SCNT) made it possible to generate diploid embryonic stem cells, which opens up the way to make high-quality pluripotent stem cells. However, the process is highly inefficient and hence expensive compared to the generation of iPSC. Even with the latest SCNT technology, we are not sure whether one can make therapeutic quality pluripotent stem cell from any patient's somatic cells or by using oocytes from any donor. Combining iPSC technology with SCNT, that is, by using the nucleus of the candidate somatic cell which got reprogrammed to pluripotent state instead that of the unmodified nucleus of the candidate somatic cell, would boost the efficiency of the technique, and we would be able to generate therapeutic quality pluripotent stem cells. Induced pluripotent stem cell nuclear transfer (iPSCNT) combines the efficiency of iPSC generation with the speed and natural reprogramming environment of SCNT. The new technique may be called iPSCNT. This technique could prove to have very revolutionary benefits for humankind. This could be useful in generating organs for transplantation for patients and for reproductive cloning, especially for childless men and women who cannot have children by any other techniques. When combined with advanced gene editing techniques (such as CRISPR-Cas system) this technique might also prove useful to those who want to have healthy children but suffer from inherited diseases. The current code of ethics may be against reproductive cloning. However, this will change with time as it happened with most of the revolutionary scientific breakthroughs. After all, it is the right of every human to have healthy offspring and it is the question of

  20. Mucin-Inspired Thermoresponsive Synthetic Hydrogels Induce Stasis in Human Pluripotent Stem Cells and Human Embryos

    Science.gov (United States)

    2016-01-01

    Human pluripotent stem cells (hPSCs; both embryonic and induced pluripotent) rapidly proliferate in adherent culture to maintain their undifferentiated state. However, for mammals exhibiting delayed gestation (diapause), mucin-coated embryos can remain dormant for days or months in utero, with their constituent PSCs remaining pluripotent under these conditions. Here we report cellular stasis for both hPSC colonies and preimplantation embryos immersed in a wholly synthetic thermoresponsive gel comprising poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) [PGMA55-PHPMA135] diblock copolymer worms. This hydroxyl-rich mucin-mimicking nonadherent 3D gel maintained PSC viability and pluripotency in the quiescent G0 state without passaging for at least 14 days. Similarly, gel-coated human embryos remain in a state of suspended animation (diapause) for up to 8 days. The discovery of a cryptic cell arrest mechanism for both hPSCs and embryos suggests an important connection between the cellular mechanisms that evoke embryonic diapause and pluripotency. Moreover, such synthetic worm gels offer considerable utility for the short-term (weeks) storage of either pluripotent stem cells or human embryos without cryopreservation.

  1. Pluripotency and differentiation of cells from human testicular sperm extraction: An investigation of cell stemness.

    Science.gov (United States)

    Sadeghian-Nodoushan, Fatemeh; Aflatoonian, Reza; Borzouie, Zahra; Akyash, Fatemeh; Fesahat, Farzaneh; Soleimani, Mehrdad; Aghajanpour, Samaneh; Moore, Harry D; Aflatoonian, Behrouz

    2016-04-01

    Human male germ-line stem cells (hmGSCs) and human testis-derived embryonic stem cell-like (htESC-like) cells are claimed to be in vitro pluripotent counterparts of spermatogonial stem cells (SSCs), but the origin and pluripotency of human testis-derived cell cultures are still under debate. The aim of this study was to generate putative pluripotent stem cells in vitro from human testicular sperm-extracted (TESE) samples of infertile men, and to assess their pluripotency and capacity to differentiate. TESE samples were minced, enzymatically disaggregated and dispersed into single-cell or cluster suspensions, and then cultured. Initially, cell clusters resembled those described for hmGSCs and htESC-like cells, and were positive for markers such as OCT4/POU5F1, NANOG, and TRA-2-54. Prolonged propagation of cell clusters expressing pluripotency markers did not thrive; instead, the cells that emerged possessed characteristics of mesenchymal stromal cells (MSCs) such as STRO-1, CD105/EGLN1, CD13/ANPEP, SOX9, vimentin, and fibronectin. KIT, SOX2, and CD44 were not expressed by these MSCs. The multipotential differentiation capacity of these cells was confirmed using Oil Red-O and Alizarin Red staining after induction with specific culture conditions. It is therefore concluded that pluripotent stem cells could not be derived using the conditions previously reported to be successful for TESE samples. PMID:27077675

  2. Mucin-Inspired Thermoresponsive Synthetic Hydrogels Induce Stasis in Human Pluripotent Stem Cells and Human Embryos.

    Science.gov (United States)

    Canton, Irene; Warren, Nicholas J; Chahal, Aman; Amps, Katherine; Wood, Andrew; Weightman, Richard; Wang, Eugenia; Moore, Harry; Armes, Steven P

    2016-02-24

    Human pluripotent stem cells (hPSCs; both embryonic and induced pluripotent) rapidly proliferate in adherent culture to maintain their undifferentiated state. However, for mammals exhibiting delayed gestation (diapause), mucin-coated embryos can remain dormant for days or months in utero, with their constituent PSCs remaining pluripotent under these conditions. Here we report cellular stasis for both hPSC colonies and preimplantation embryos immersed in a wholly synthetic thermoresponsive gel comprising poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) [PGMA55-PHPMA135] diblock copolymer worms. This hydroxyl-rich mucin-mimicking nonadherent 3D gel maintained PSC viability and pluripotency in the quiescent G0 state without passaging for at least 14 days. Similarly, gel-coated human embryos remain in a state of suspended animation (diapause) for up to 8 days. The discovery of a cryptic cell arrest mechanism for both hPSCs and embryos suggests an important connection between the cellular mechanisms that evoke embryonic diapause and pluripotency. Moreover, such synthetic worm gels offer considerable utility for the short-term (weeks) storage of either pluripotent stem cells or human embryos without cryopreservation. PMID:27163030

  3. Mga is essential for the survival of pluripotent cells during peri-implantation development.

    Science.gov (United States)

    Washkowitz, Andrew J; Schall, Caroline; Zhang, Kun; Wurst, Wolfgang; Floss, Thomas; Mager, Jesse; Papaioannou, Virginia E

    2015-01-01

    The maintenance and control of pluripotency is of great interest in stem cell biology. The dual specificity T-box/basic-helix-loop-helix-zipper transcription factor Mga is expressed in the pluripotent cells of the inner cell mass (ICM) and epiblast of the peri-implantation mouse embryo, but its function has not been investigated previously. Here, we use a loss-of-function allele and RNA knockdown to demonstrate that Mga depletion leads to the death of proliferating pluripotent ICM cells in vivo and in vitro, and the death of embryonic stem cells (ESCs) in vitro. Additionally, quiescent pluripotent cells lacking Mga are lost during embryonic diapause. Expression of Odc1, the rate-limiting enzyme in the conversion of ornithine into putrescine in the synthesis of polyamines, is reduced in Mga mutant cells, and the survival of mutant ICM cells as well as ESCs is rescued in culture by the addition of exogenous putrescine. These results suggest a mechanism whereby Mga influences pluripotent cell survival through regulation of the polyamine pool in pluripotent cells of the embryo, whether they are in a proliferative or quiescent state. PMID:25516968

  4. Embryonic hybrid cells: a powerful tool for studying pluripotency and reprogramming of the differentiated cell chromosomes

    Directory of Open Access Journals (Sweden)

    SEROV OLEG

    2001-01-01

    Full Text Available The properties of embryonic hybrid cells obtained by fusion of embryonic stem (ES or teratocarcinoma (TC cells with differentiated cells are reviewed. Usually, ES-somatic or TC-somatic hybrids retain pluripotent capacity at high levels quite comparable or nearly identical with those of the pluripotent partner. When cultured in vitro, ES-somatic- and TC-somatic hybrid cell clones, as a rule, lose the chromosomes derived from the somatic partner; however, in some clones the autosomes from the ES cell partner were also eliminated, i.e. the parental chromosomes segregated bilaterally in the ES-somatic cell hybrids. This opens up ways for searching correlation between the pluripotent status of the hybrid cells and chromosome segregation patterns and therefore for identifying the particular chromosomes involved in the maintenance of pluripotency. Use of selective medium allows to isolate in vitro the clones of ES-somatic hybrid cells in which "the pluripotent" chromosome can be replaced by "the somatic" counterpart carrying the selectable gene. Unlike the TC-somatic cell hybrids, the ES-somatic hybrids with a near-diploid complement of chromosomes are able to contribute to various tissues of chimeric animals after injection into the blastocoel cavity. Analysis of the chimeric animals showed that the "somatic" chromosome undergoes reprogramming during development. The prospects for the identification of the chromosomes that are involved in the maintenance of pluripotency and its cis- and trans-regulation in the hybrid cell genome are discussed.

  5. Association of telomere length with authentic pluripotency of ES/iPS cells

    Institute of Scientific and Technical Information of China (English)

    Junjiu Huang; William W Ge; John CM Tsibris; David L Keefe; Lin Liu; Fang Wang; Maja Okuka; Na Liu; Guangzhen Ji; Xiaoying Ye; Bingfeng Zuo; Minshu Li; Ping Liang

    2011-01-01

    Telomerase and telomeres are important for indefinite replication of stem cells. Recently, telomeres of somatic cells were found to be reprogrammed to elongate in induced pluripotent stem cells(iPSCs). The role of telomeres in developmental pluripotency in vivo of embryonic stem cells(ESCs)or iPSCs, however, has not been directly addressed.We show that ESCs with long telomeres exhibit authentic developmental pluripotency, as evidenced by generation of complete ESC pups as well as germline-competent chimeras, the most stringent tests available in rodents. ESCs with short telomeres show reduced teratoma formation and chimera production, and fail to generate complete ESC pups. Telomere lengths are highly correlated(r>0.8)with the developmental pluripotency of ESCs. Short telomeres decrease the proliferative rate or capacity of ESCs, alter the expression of genes related to telomere epigenetics,down-regulate genes important for embryogenesis and disrupt germ cell differentiation. Moreover, iPSCs with longer telomeres generate chimeras with higher efficiency than those with short telomeres. Our data show that functional telomeres are essential for the developmental pluripotency of ESCs/iPSCs and suggest that telomere length may provide a valuable marker to evaluate stem cell pluripotency, particularly when the stringent tests are not feasible.

  6. Developmental complexity of early mammalian pluripotent cell populations in vivo and in vitro.

    Science.gov (United States)

    Pelton, T A; Bettess, M D; Lake, J; Rathjen, J; Rathjen, P D

    1998-01-01

    Early mammalian embryogenesis is characterised by the coordinated proliferation, differentiation, migration and apoptosis of a pluripotent cell pool that is able to give rise to extraembryonic lineages and all the cell types of the embryo proper. These cells retain pluripotent differentiation capability, defined in this paper as the ability to form all cell types of the embryo and adult, until differentiation into the three embryonic germ layers at gastrulation. Our understanding of pluripotent cell biology and molecular regulation has been hampered by the difficulties associated with experimental manipulation of these cells in vivo. However, a more detailed understanding of pluripotent cell behaviour is emerging from the application of molecular technologies to early mouse embryogenesis. The construction of mouse mutants by gene targeting, mapping of gene expression in vivo, and modelling of cell decisions in vitro are providing insight into the cellular origin, identity and action of key developmental regulators, and the nature of pluripotent cells themselves. In this review we discuss the properties of early embryonic pluripotent cells in vitro and in vivo, focusing on progression from inner cell mass (ICM) cells in the blastocyst to the onset of gastrulation. PMID:10612459

  7. Genome-wide chromatin interactions of the Nanog locus in pluripotency, differentiation, and reprogramming.

    Science.gov (United States)

    Apostolou, Effie; Ferrari, Francesco; Walsh, Ryan M; Bar-Nur, Ori; Stadtfeld, Matthias; Cheloufi, Sihem; Stuart, Hannah T; Polo, Jose M; Ohsumi, Toshiro K; Borowsky, Mark L; Kharchenko, Peter V; Park, Peter J; Hochedlinger, Konrad

    2013-06-01

    The chromatin state of pluripotency genes has been studied extensively in embryonic stem cells (ESCs) and differentiated cells, but their potential interactions with other parts of the genome remain largely unexplored. Here, we identified a genome-wide, pluripotency-specific interaction network around the Nanog promoter by adapting circular chromosome conformation capture sequencing. This network was rearranged during differentiation and restored in induced pluripotent stem cells. A large fraction of Nanog-interacting loci were bound by Mediator or cohesin in pluripotent cells. Depletion of these proteins from ESCs resulted in a disruption of contacts and the acquisition of a differentiation-specific interaction pattern prior to obvious transcriptional and phenotypic changes. Similarly, the establishment of Nanog interactions during reprogramming often preceded transcriptional upregulation of associated genes, suggesting a causative link. Our results document a complex, pluripotency-specific chromatin "interactome" for Nanog and suggest a functional role for long-range genomic interactions in the maintenance and induction of pluripotency. PMID:23665121

  8. Evolution of contemporary museum architecture

    OpenAIRE

    Bilous, Yulia

    2013-01-01

    This article deals with the development of museum architecture from the formation of the classic building architecture to the establishment of the contemporary museum architecture. Changes in the museum building architecture and displaying principles have been analysed. The 19th century was defined by the emergence of a vast number of museums serving through present as examples of the contemporary museum architecture. New styles are tried in the museum architecture alo...

  9. Hybrid architecture: object, landscape, infrastructure

    OpenAIRE

    Pinto de Freitas, Rita

    2011-01-01

    The concept of "hybrid architecture" developed in this study considers hybrid all architecture that is at once object, landscape and infrastructure. Hybrid architecture, pushed by the fact that it concentrates in a single architectural intervention a triple object-, landscape- and infrastructure-related nature, generates architectural answers with very specific features, and its study achieves following goals: 1: Clarify the term hybrid related to architectural intervention; 2: Tran...

  10. Business Capabilities Centric Enterprise Architecture

    OpenAIRE

    Barroero, Thiago; Motta, Gianmario; Pignatelli, Giovanni

    2010-01-01

    In the field of Enterprise Architecture, The Open Group Architecture Framework (TOGAF) is a well known framework, that links Business Architecture, Data Architecture, Application Architecture, Technology. A key concept within Business Architecture domain is Business Capabilities, that are delivered by Business Component (BC). A BC is a business unit that encompasses a coherent set of activities, supported by assets including people, processes and technology. Current TOGAF version recognizes t...

  11. Data-Centric Enterprise Architecture

    OpenAIRE

    Zeinab Rajabi; Maryam Nooraei Abade

    2012-01-01

    Enterprises choose Enterprise Architecture (EA) solution, in order to overcome dynamic business challenges and in coordinate various enterprise elements. In this article, a solution is suggested for the Enterprise Architecture development. The solution focuses on architecture data in the Enterprise Architecture development process. Data-centric architecture approach is preferred product-centric architecture approach. We suggest using Enterprise Ontology (EO) as context for collecting architec...

  12. On Detailing in Contemporary Architecture

    DEFF Research Database (Denmark)

    Kristensen, Claus; Kirkegaard, Poul Henning

    Details in architecture have a significant influence on how architecture is experienced. One can touch the materials and analyse the detailing - thus details give valuable information about the architectural scheme as a whole. The absence of perceptual stimulation like details and materiality...... / tactility can blur the meaning of the architecture and turn it into an empty statement. The present paper will outline detailing in contemporary architecture and discuss the issue with respect to architectural quality. Architectural cases considered as sublime piece of architecture will be presented and...... discussed with respect to the meaning of detailing....

  13. Integrated Data Assimilation Architecture Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Integrated Data Assimilation Architecture (IDAA) is a middleware architecture that facilitates the incorporation of heterogeneous sensing and control devices...

  14. Avionics Architecture for Exploration Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Avionics Architectures for Exploration Project team will develop a system level environment and architecture that will accommodate equipment from multiple...

  15. Computer architecture technology trends

    CERN Document Server

    1991-01-01

    Please note this is a Short Discount publication. This year's edition of Computer Architecture Technology Trends analyses the trends which are taking place in the architecture of computing systems today. Due to the sheer number of different applications to which computers are being applied, there seems no end to the different adoptions which proliferate. There are, however, some underlying trends which appear. Decision makers should be aware of these trends when specifying architectures, particularly for future applications. This report is fully revised and updated and provides insight in

  16. Architecture, energy and climate

    DEFF Research Database (Denmark)

    Lauring, Michael

    2010-01-01

    Architecture has always had to relate to climatic conditions while providing shelter from the sun, the rain, the winds or the cold. This is a main purpose of buildings: To establish an indoor climate different from the outdoor. In the Nordic countries fuels for heating buildings has been a vital...... cases been to search for traditional and pre-industrialized ways of building and settlement. The idea of this theme number is not to flee from modern life and approaches, but instead to face modern conditions relevant in achieving sustainable urban development and sustainable architecture, the only...... truly modern architecture that exists....

  17. Architecture for Verifiable Software

    Science.gov (United States)

    Reinholtz, William; Dvorak, Daniel

    2005-01-01

    Verifiable MDS Architecture (VMA) is a software architecture that facilitates the construction of highly verifiable flight software for NASA s Mission Data System (MDS), especially for smaller missions subject to cost constraints. More specifically, the purpose served by VMA is to facilitate aggressive verification and validation of flight software while imposing a minimum of constraints on overall functionality. VMA exploits the state-based architecture of the MDS and partitions verification issues into elements susceptible to independent verification and validation, in such a manner that scaling issues are minimized, so that relatively large software systems can be aggressively verified in a cost-effective manner.

  18. RECONSTRUCTING DECONSTRUCTION IN ARCHITECTURE

    Directory of Open Access Journals (Sweden)

    IDHAM Noor Cholis

    2013-01-01

    Full Text Available This paper examines deconstruction in architecture and forms used, which triggered by dispute of form and its scientification claimed by deconstructivists. Deconstruction terminologyis studied in the first part related to architecture field as a base knowledge. Some sample works of known deconstructionist architects are assessed in order to understand how their building is deconstructed and what forms they used. Discussion about form and its relation to other fields is then pursued by discussing the involvement of terminology of science, aesthetic pattern, and human life. The results of this discussion give clear understanding how form related to deconstruction in architecture are used.

  19. Statistics of genome architecture

    International Nuclear Information System (INIS)

    The main statistical distributions applicable to the analysis of genome architecture and genome tracks are briefly discussed and critically assessed. Although the observed features in distributions of element lengths can be equally well fitted by the different statistical approximations, the interpretation of observed regularities may strongly depend on the chosen scheme. We discuss the possible evolution scenarios and describe the main characteristics obtained with different distributions. The expression for the assessment of levels in hierarchical chromatin folding is derived and the quantitative measure of genome architecture inhomogeneity is suggested. This theory provides the ground for the regular statistical study of genome architecture and genome tracks.

  20. Mixed Reality Architecture: a dynamic architectural topology

    OpenAIRE

    Schnädelbach, H.; A Penn; Steadman, P.

    2007-01-01

    Architecture can be shown to structure patterns of co-presence and in turn to be structured itself by the rules and norms of the society present within it. This two-way relationship exists in a surprisingly stable framework, as fundamental changes to buildings are slow and costly. At the same time, change within organisations is increasingly rapid and buildings are used to accommodate some of that change. This adaptation can be supported by the use of telecommunication technolo...

  1. Robot Electronics Architecture

    Science.gov (United States)

    Garrett, Michael; Magnone, Lee; Aghazarian, Hrand; Baumgartner, Eric; Kennedy, Brett

    2008-01-01

    An electronics architecture has been developed to enable the rapid construction and testing of prototypes of robotic systems. This architecture is designed to be a research vehicle of great stability, reliability, and versatility. A system according to this architecture can easily be reconfigured (including expanded or contracted) to satisfy a variety of needs with respect to input, output, processing of data, sensing, actuation, and power. The architecture affords a variety of expandable input/output options that enable ready integration of instruments, actuators, sensors, and other devices as independent modular units. The separation of different electrical functions onto independent circuit boards facilitates the development of corresponding simple and modular software interfaces. As a result, both hardware and software can be made to expand or contract in modular fashion while expending a minimum of time and effort.

  2. DSP Architecture Design Essentials

    CERN Document Server

    Marković, Dejan

    2012-01-01

    In DSP Architecture Design Essentials, authors Dejan Marković and Robert W. Brodersen cover a key subject for the successful realization of DSP algorithms for communications, multimedia, and healthcare applications. The book addresses the need for DSP architecture design that maps advanced DSP algorithms to hardware in the most power- and area-efficient way. The key feature of this text is a design methodology based on a high-level design model that leads to hardware implementation with minimum power and area. The methodology includes algorithm-level considerations such as automated word-length reduction and intrinsic data properties that can be leveraged to reduce hardware complexity. From a high-level data-flow graph model, an architecture exploration methodology based on linear programming is used to create an array of architectural solutions tailored to the underlying hardware technology. The book is supplemented with online material: bibliography, design examples, CAD tutorials and custom software.

  3. Greek architecture now

    DEFF Research Database (Denmark)

    Skousbøll, Karin Merete

    2006-01-01

    With the author's Scandinavian viewpoint the aim of this book has been an investigation into contemporary Greek architecture and at the same time providing an understanding for its essential characteristics based on the historic, cultural heritage of Hellas....

  4. Analyzing architecture articles

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In the present study, we express the quality, function, and characteristics of architecture to help people comprehensively understand what architecture is. We also reveal the problems and conflict found in population, land, water resources, pollution, energy, and the organization systems in construction. China’s economy is transforming. We should focus on the cities, architectural environment, energy conservation, emission-reduction, and low-carbon output that will result in successful green development. We should macroscopically and microscopically analyze the development, from the natural environment to the artificial environment; from the relationship between human beings and nature to the combination of social ecology in cities, and farmlands. We must learn to develop and control them harmoniously and scientifically to provide a foundation for the methods used in architecture research.

  5. Adaptive Architectural Envelope

    DEFF Research Database (Denmark)

    Foged, Isak Worre; Kirkegaard, Poul Henning

    2010-01-01

    Recent years have seen an increasing variety of applications of adaptive architectural structures for improvement of structural performance by recognizing changes in their environments and loads, adapting to meet goals, and using past events to improve future performance or maintain serviceability....... The general scopes of this paper are to develop a new adaptive kinetic architectural structure, particularly a reconfigurable architectural structure which can transform body shape from planar geometries to hyper-surfaces using different control strategies, i.e. a transformation into more than one or...... two different shape alternatives. The adaptive structure is a proposal for a responsive building envelope which is an idea of a first level operational framework for present and future investigations towards performance based responsive architectures through a set of responsive typologies. A mock- up...

  6. Architectural Competition and BIM

    DEFF Research Database (Denmark)

    Sørensen, Nils Lykke; Frandsen, Anne Kathrine; Øien, Turid Borgestrand

    2015-01-01

    on architecturalcompetitions, a series of interviews was conducted with building clients as well as architects, focusing on the impact of the above-mentioned changes within the building sector on architectural competitions as an institution. In the interviews, ICT and notleast BIM was a recurring...... clients, architects and client consultants) and the applied technologies (competition forms, ICT tools, directives) in architectural competitions in a theoretical actor-network perspective. The diverging understandings of the role of BIM are demonstrating one of many negotiations in progress in the...... network of architectural competitions. BIM is transformed from an inscription device visually representing the competition proposals to form an actant that challenges the very concept of architectural competition. The objective of the paper is to contribute to theunderstanding of BIM used in the kind of...

  7. Isolation of adult human pluripotent stem cells from mesenchymal cell populations and their application to liver damages.

    Science.gov (United States)

    Wakao, Shohei; Kitada, Masaaki; Kuroda, Yasumasa; Dezawa, Mari

    2012-01-01

    We have found a novel type of pluripotent stem cells, Multilineage-differentiating stress enduring (Muse) cells that can be isolated from mesenchymal cell populations. Muse cells are characterized by stress tolerance, expression of pluripotency markers, self-renewal, and the ability to differentiate into endodermal-, mesodermal-, and ectodermal-lineage cells from a single cell, demonstrating that they are pluripotent stem cells. They can be isolated as cells positive for stage-specific embryonic antigen-3, a human pluripotent stem cell marker. Here, we introduce the isolation method for Muse cells and the effect of transplantation of these cells on chronic liver diseases. PMID:22167642

  8. Analysis of Architecture Pattern Usage in Legacy System Architecture Documentation

    NARCIS (Netherlands)

    Harrison, Neil B.; Avgeriou, Paris

    2008-01-01

    Architecture patterns are an important tool in architectural design. However, while many architecture patterns have been identified, there is little in-depth understanding of their actual use in software architectures. For instance, there is no overview of how many patterns are used per system or wh

  9. Redesigning architecture through photography

    OpenAIRE

    Germen, Murat

    2008-01-01

    Abstract – This paper focuses on the possibility of (re)designing architecture virtually with the help of one of the most important representation tools: Photography. Various digital processes like stitching multiple photos together and mirroring images in image editing software like Photoshop, allow this virtual architecture to take place in virtual environments. Photography can be utilized in the process of ‘constructing’ a new space --that we can call ‘narrative space’-- from an existing s...

  10. Essential software architecture

    CERN Document Server

    Gorton, Ian

    2011-01-01

    Job titles like ""Technical Architect"" and ""Chief Architect"" nowadays abound in software industry, yet many people suspect that ""architecture"" is one of the most overused and least understood terms in professional software development. Gorton's book tries to resolve this dilemma. It concisely describes the essential elements of knowledge and key skills required to be a software architect. The explanations encompass the essentials of architecture thinking, practices, and supporting technologies. They range from a general understanding of structure and quality attributes through technical i

  11. Generic Distributed Simulation Architecture

    Energy Technology Data Exchange (ETDEWEB)

    Booker, C.P.

    1999-05-14

    A Generic Distributed Simulation Architecture is described that allows a simulation to be automatically distributed over a heterogeneous network of computers and executed with very little human direction. A prototype Framework is presented that implements the elements of the Architecture and demonstrates the feasibility of the concepts. It provides a basis for a future, improved Framework that will support legacy models. Because the Framework is implemented in Java, it may be installed on almost any modern computer system.

  12. Pushing architectural quality further

    OpenAIRE

    Laverge, Jelle; Van Den Bossche, Nathan; Janssens, Arnold

    2008-01-01

    In this paper, the intentions thriving the implementation of computational modeling of building physics as it is approached in the Architectural engineering courses at Ghent University are discussed. During the bachelor degree, courses focus mainly on integration of basic building physics feasibility in the architectural conceptualization. During the final bachelor year, students program their own simplified 2D models for internal condensation and thermal bridges in a spreadsheet, based on...

  13. Climate and architecture

    DEFF Research Database (Denmark)

    Tind Kristensen, Eva; Friis Møller, Winnie; Rotne, Georg;

    2010-01-01

    Climate and Architecture analyserer klimaets rolle i arkitekturen. Intentionen med bogen er at pege på nogle af de mange muligheder for bygningers klimaregulering, som et mere detaljeret studie af de lokale klimatiske forhold og den stedlige byggeskik tilbyder.......Climate and Architecture analyserer klimaets rolle i arkitekturen. Intentionen med bogen er at pege på nogle af de mange muligheder for bygningers klimaregulering, som et mere detaljeret studie af de lokale klimatiske forhold og den stedlige byggeskik tilbyder....

  14. Digitally-Driven Architecture

    OpenAIRE

    Henriette Bier; Terry Knight

    2014-01-01

    The shift from mechanical to digital forces architects to reposition themselves: Architects generate digital information, which can be used not only in designing and fabricating building components but also in embedding behaviours into buildings. This implies that, similar to the way that industrial design and fabrication with its concepts of standardisation and serial production influenced modernist architecture, digital design and fabrication influences contemporary architecture. While stan...

  15. Models of Architecture

    OpenAIRE

    Pelcat, Maxime; Desnos, Karol; Maggiani, Luca; Liu, Yanzhou; Heulot, Julien; Nezan, Jean-François; Bhattacharyya, Shuvra S.

    2015-01-01

    The current trend in high performance and embedded computing consists of designing increasingly complex heterogeneous hardware architectures with non-uniform communication resources. In order to take hardware and software design decisions, early evaluations of the system non-functional properties are needed. These evaluations of system efficiency require high-level information on both the algorithms and the architecture. In state of the art Model Driven Engineering (MDE) methods, different co...

  16. Aesthetics of sustainable architecture

    OpenAIRE

    Lee, S.

    2011-01-01

    The purpose of this book is to reveal, explore and further the debate on the aesthetic potentials of sustainable architecture and its practice. This book opens a new area of scholarship and discourse in the design and production of sustainable architecture, one that is based in aesthetics. The chapters in this book have been compiled from architects and scholars working in diverse research and practice areas in North America, Europe, the Middle East and Asia. While they approach the subject m...

  17. Artificial cognition architectures

    CERN Document Server

    Crowder, James A; Friess, Shelli A

    2013-01-01

    The goal of this book is to establish the foundation, principles, theory, and concepts that are the backbone of real, autonomous Artificial Intelligence. Presented here are some basic human intelligence concepts framed for Artificial Intelligence systems. These include concepts like Metacognition and Metamemory, along with architectural constructs for Artificial Intelligence versions of human brain functions like the prefrontal cortex. Also presented are possible hardware and software architectures that lend themselves to learning, reasoning, and self-evolution

  18. ARCHITECTURE IN THE ISLAMIC CIVILIZATION: MUSLIM BUILDING OR ISLAMIC ARCHITECTURE

    Directory of Open Access Journals (Sweden)

    Ayat Ali Yassin

    2012-12-01

    Full Text Available The main problem of the theory in the arena of islamic architecture is affected by some of its Westernthoughts, and stereotyping the islamic architecture according to Western thoughts; this leads to the breakdownof the foundations in the islamic architecture. It is a myth that islamic architecture is subjected to theinfluence from foreign architectures. This paper will highlight the dialectical concept of islamic architecture ormuslim buildings and the areas of recognition in islamic architecture. It will also widen the knowledge in thecharacteristics of each point in time according to the stages of islamic architecture from the prophetic agemoving through the architecture outside the city of Medina, the Caliphs, the Umayyad, Abbasid, andarchitectural models by spatial and time periods, taking Iraq as the example to explain how the Islam influentson architecture and vice versa.

  19. Reverse engineering human neurodegenerative disease using pluripotent stem cell technology.

    Science.gov (United States)

    Liu, Ying; Deng, Wenbin

    2016-05-01

    With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new "windows of opportunity" for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what׳s wrong in the neurodegenerative disease process in the "disease-in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to

  20. Reprogramming T cell Lymphocytes to Induced Pluripotent Stem Cells

    Science.gov (United States)

    Bared, Kalia

    The discovery of induced pluripotent stem cells (iPSC) provided a novel technology for the study of development and pharmacology and complement embryonic stem cells (ES) for cell therapy applications. Though iPSC are derived from adult tissue they are comparable to ES cells in their behavior; multi-lineage differentiation and self-renewal. This makes iPSC research appealing because they can be studied in great detail and expanded in culture broadly. Fibroblasts were the first cell type reprogrammed to an iPSC using a retrovirus vector, since then alternative cell types including lymphocytes have been used to generate iPSC. Different types of vectors have also been developed to enhance iPSC formation and quality. However, specific T lymphocyte subsets have not been shown to reprogram to a pluripotent state to date. Here, we proposed to derive iPSC from peripheral blood effector and central memory T cells, reasoning that the resultant iPSC will maintain the epigenetic memory of a T lymphocyte, including the T cell receptor (TCR) gene rearrangement. This epigenetic memory will enable the differentiation and expansion of T cell iPSC into professional T cells containing a specific TCR. These could then be used for cell therapy to target specific antigens, as well as to improve culture techniques to expand T cells in vitro. We studied different gene delivery methods to derive iPSC from different types of T lymphocytes. We assessed the viability of viral transduction using flow cytometry to detect green fluorescent marker contained in the viral construct and quantitative real time polymerase chain reaction (qRT-PCR) to detect Oct4, Klf4, Sox2, and c-Myc gene expression. Our results demonstrate that the Sendai virus construct is the most feasible platform to reprogram T lymphocytes. We anticipate that this platform will provide an efficient and safe approach to derive iPSC from different T cell subsets, including memory T cells.

  1. Utilizing the Central Courtyard of Traditional Architecture in Modern Architecture

    OpenAIRE

    Javad Samadi

    2014-01-01

    The purpose of this study is utilizing the central courtyard of traditional architecture in modern architecture. Since the nineteenth century, the traditional architecture has been more taken into account. From this time period, the sixties century is significantly important. The studies on the traditional architecture were conducted and followed in this period with the new objective and attitude. Until the early sixties century, most of the studies on the traditional architecture were briefl...

  2. Pluripotent State Induction in Mouse Embryonic Fibroblast Using mRNAs of Reprogramming Factors

    Directory of Open Access Journals (Sweden)

    Ahmed Kamel El-Sayed

    2014-11-01

    Full Text Available Reprogramming of somatic cells has great potential to provide therapeutic treatments for a number of diseases as well as provide insight into mechanisms underlying early embryonic development. Improvement of induced Pluripotent Stem Cells (iPSCs generation through mRNA-based methods is currently an area of intense research. This approach provides a number of advantages over previously used methods such as DNA integration and insertional mutagenesis. Using transfection of specifically synthesized mRNAs of various pluripotency factors, we generated iPSCs from mouse embryonic fibroblast (MEF cells. The genetic, epigenetic and functional properties of the iPSCs were evaluated at different times during the reprogramming process. We successfully introduced synthesized mRNAs, which localized correctly inside the cells and exhibited efficient and stable translation into proteins. Our work demonstrated a robust up-regulation and a gradual promoter de-methylation of the pluripotency markers, including non-transfected factors such as Nanog, SSEA-1 (stage-specific embryonic antigen 1 and Rex-1 (ZFP-42, zinc finger protein 42. Using embryonic stem cells (ESCs conditions to culture the iPS cells resulted in formation of ES-like colonies after approximately 12 days with only five daily repeated transfections. The colonies were positive for alkaline phosphatase and pluripotency-specific markers associated with ESCs. This study revealed the ability of pluripotency induction and generation of mouse mRNA induced pluripotent stem cells (mRNA iPSCs using transfection of specifically synthesized mRNAs of various pluripotency factors into mouse embryonic fibroblast (MEF cells. These generated iPSCs exhibited molecular and functional properties similar to ESCs, which indicate that this method is an efficient and viable alternative to ESCs and can be used for further biological, developmental and therapeutic investigations.

  3. A continuum of cell states spans pluripotency and lineage commitment in human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Shelley R Hough

    Full Text Available BACKGROUND: Commitment in embryonic stem cells is often depicted as a binary choice between alternate cell states, pluripotency and specification to a particular germ layer or extraembryonic lineage. However, close examination of human ES cell cultures has revealed significant heterogeneity in the stem cell compartment. METHODOLOGY/PRINCIPAL FINDINGS: We isolated subpopulations of embryonic stem cells using surface markers, then examined their expression of pluripotency genes and lineage specific transcription factors at the single cell level, and tested their ability to regenerate colonies of stem cells. Transcript analysis of single embryonic stem cells showed that there is a gradient and a hierarchy of expression of pluripotency genes in the population. Even cells at the top of the hierarchy generally express only a subset of the stem cell genes studied. Many cells co-express pluripotency and lineage specific genes. Cells along the continuum show a progressively decreasing likelihood of self renewal as their expression of stem cell surface markers and pluripotency genes wanes. Most cells that are positive for stem cell surface markers express Oct-4, but only those towards the top of the hierarchy express the nodal receptor TDGF-1 and the growth factor GDF3. SIGNIFICANCE: These findings on gene expression in single embryonic stem cells are in concert with recent studies of early mammalian development, which reveal molecular heterogeneity and a stochasticity of gene expression in blastomeres. Our work indicates that only a small fraction of the population resides at the top of the hierarchy, that lineage priming (co-expression of stem cell and lineage specific genes characterizes pluripotent stem cell populations, and that extrinsic signaling pathways are upstream of transcription factor networks that control pluripotency.

  4. Discussing performance management architecture in public service broadcasting

    DEFF Research Database (Denmark)

    Tambo, Torben; Gabel, Ole Dahl

    2014-01-01

    Purpose: To demonstrate design of Performance Management (PM) processes in highly complex, non-profit, culture-producing organisations specifically the shift from Performance Management Systems (PMS) to Performance Management Architectures (PMA) specifically using Danish Broadcasting Corporation...... metrics, reflected in an architecture, raises the certainty and level of organisational consensus. Research limitations/implications: DR is unique as the largest cultural institution in the Danish language area backed by a political consensus, strong popular support, high level of funding and a...

  5. Second International Workshop on Variability in Software Architecture

    OpenAIRE

    Galster, Matthias; Avgeriou, Paris; Weyns, Danny; Becker, Martin

    2012-01-01

    Variability is the ability of a software system or artifact to be adapted for specific contexts, in a preplanned manner. Many of today's software systems are built with variability in mind, e.g., product lines and families, self-adaptive systems, open platforms, or service-based systems that support dynamic runtime composition of web services. Variability is reflected in and facilitated through the software architecture. Also, as the software architecture is a reference point for many develop...

  6. Reprogramming human B cells into induced pluripotent stem cells and its enhancement by C/EBPα.

    Science.gov (United States)

    Bueno, C; Sardina, J L; Di Stefano, B; Romero-Moya, D; Muñoz-López, A; Ariza, L; Chillón, M C; Balanzategui, A; Castaño, J; Herreros, A; Fraga, M F; Fernández, A; Granada, I; Quintana-Bustamante, O; Segovia, J C; Nishimura, K; Ohtaka, M; Nakanishi, M; Graf, T; Menendez, P

    2016-03-01

    B cells have been shown to be refractory to reprogramming and B-cell-derived induced pluripotent stem cells (iPSC) have only been generated from murine B cells engineered to carry doxycycline-inducible Oct4, Sox2, Klf4 and Myc (OSKM) cassette in every tissue and from EBV/SV40LT-immortalized lymphoblastoid cell lines. Here, we show for the first time that freshly isolated non-cultured human cord blood (CB)- and peripheral blood (PB)-derived CD19+CD20+ B cells can be reprogrammed to iPSCs carrying complete VDJH immunoglobulin (Ig) gene monoclonal rearrangements using non-integrative tetracistronic, but not monocistronic, OSKM-expressing Sendai Virus. Co-expression of C/EBPα with OSKM facilitates iPSC generation from both CB- and PB-derived B cells. We also demonstrate that myeloid cells are much easier to reprogram than B and T lymphocytes. Differentiation potential back into the cell type of their origin of B-cell-, T-cell-, myeloid- and fibroblast-iPSCs is not skewed, suggesting that their differentiation does not seem influenced by 'epigenetic memory'. Our data reflect the actual cell-autonomous reprogramming capacity of human primary B cells because biased reprogramming was avoided by using freshly isolated primary cells, not exposed to cytokine cocktails favoring proliferation, differentiation or survival. The ability to reprogram CB/PB-derived primary human B cells offers an unprecedented opportunity for studying developmental B lymphopoiesis and modeling B-cell malignancies. PMID:26500142

  7. Modeling chemotherapeutic neurotoxicity with human induced pluripotent stem cell-derived neuronal cells.

    Directory of Open Access Journals (Sweden)

    Heather E Wheeler

    Full Text Available There are no effective agents to prevent or treat chemotherapy-induced peripheral neuropathy (CIPN, the most common non-hematologic toxicity of chemotherapy. Therefore, we sought to evaluate the utility of human neuron-like cells derived from induced pluripotent stem cells (iPSCs as a means to study CIPN. We used high content imaging measurements of neurite outgrowth phenotypes to compare the changes that occur to iPSC-derived neuronal cells among drugs and among individuals in response to several classes of chemotherapeutics. Upon treatment of these neuronal cells with the neurotoxic drug paclitaxel, vincristine or cisplatin, we identified significant differences in five morphological phenotypes among drugs, including total outgrowth, mean/median/maximum process length, and mean outgrowth intensity (P < 0.05. The differences in damage among drugs reflect differences in their mechanisms of action and clinical CIPN manifestations. We show the potential of the model for gene perturbation studies by demonstrating decreased expression of TUBB2A results in significantly increased sensitivity of neurons to paclitaxel (0.23 ± 0.06 decrease in total neurite outgrowth, P = 0.011. The variance in several neurite outgrowth and apoptotic phenotypes upon treatment with one of the neurotoxic drugs is significantly greater between than within neurons derived from four different individuals (P < 0.05, demonstrating the potential of iPSC-derived neurons as a genetically diverse model for CIPN. The human neuron model will allow both for mechanistic studies of specific genes and genetic variants discovered in clinical studies and for screening of new drugs to prevent or treat CIPN.

  8. New Energy Architecture. Myanmar

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-06-15

    A global transition towards a new energy architecture is under way, driven by countries' need to respond to the changing dynamics of economic growth, environmental sustainability and energy security. The World Economic Forum, in collaboration with Accenture, has created the New Energy Architecture Initiative to address and accelerate this transition. The Initiative supports the development of national strategies and policy frameworks as countries seek to achieve the combined goals of energy security and access, sustainability, and economic growth and development. The World Economic Forum has formed a partnership with the Ministry of Energy of Myanmar to help apply the Initiative's approach to this developing and resource-rich nation. The Asian Development Bank and the World Economic Forum's Project Adviser, Accenture, have collaborated with the Forum on this consultation process, and have been supported by relevant government, industry and civil society stakeholders. The consultation process aims to understand the nation's current energy architecture challenges and provide an overview of a path to a New Energy Architecture through a series of insights. These insights could form the basis for a long-term multistakeholder roadmap to build Myanmar's energy sector in a way that is secure and sustainable, and promotes economic growth as the country makes its democratic transition. While not all recommendations can be implemented in the near term, they do provide options for creating a prioritized roadmap for Myanmar's energy transition. This report is the culmination of a nine-month multistakeholder process investigating Myanmar's energy architecture. Over the course of many visits to the country, the team has conducted numerous interviews, multistakeholder workshops, and learning and data-gathering exercises to ensure a comprehensive range of information and views. The team has also engaged with a variety of stakeholders to better

  9. Time · Space · Architecture

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In the 20th century a Swiss writer wrote a book titled Time, Space and Architecture, in which he discussed the relationship between architecture and the times. Fifty years after that, this paper adopts the same title, hoping to deepen the understanding of the space-time structure in architecture and contribute to the new exploration of architectural forms.

  10. A Reflective Look at Reflecting Teams

    Science.gov (United States)

    Pender, Rebecca L.; Stinchfield, Tracy

    2012-01-01

    This article reviewed existing literature and research on the reflecting team process. There is a dearth of empirical research that explores the reflecting team process and the outcome of counseling that uses reflecting teams. Implications of using reflecting teams for counselors, counselor educators, and clients will be discussed. A call for…

  11. Data-Centric Enterprise Architecture

    Directory of Open Access Journals (Sweden)

    Zeinab Rajabi

    2012-08-01

    Full Text Available Enterprises choose Enterprise Architecture (EA solution, in order to overcome dynamic business challenges and in coordinate various enterprise elements. In this article, a solution is suggested for the Enterprise Architecture development. The solution focuses on architecture data in the Enterprise Architecture development process. Data-centric architecture approach is preferred product-centric architecture approach. We suggest using Enterprise Ontology (EO as context for collecting architecture data; Enterprise Ontology enhances quality of architecture data and lead to effective architecture results for decision-making. First, Enterprise is modeled using the ontology. Then how collecting Enterprise Architecture data based on the Enterprise Ontology is explained. Finally, the results and advantages of the solution are demonstrated.

  12. The business of exploiting induced pluripotent stem cells.

    Science.gov (United States)

    Prescott, Catherine

    2011-08-12

    Induced pluripotent stem cells (iPS cells) can be exploited for both research and clinical applications. The first part of this review seeks to provide an understanding of the financial drivers and key elements of a successful business strategy that underpin a company focused on developing iPS-related products and services targeted at the research market. The latter part of the review highlights some of the reasons as to why the reprogramming of somatic cells is currently being used to develop cell-based models to screen for small molecules with drug-like properties rather than to develop cell-based regenerative medicines per se. The latter may be used to repair or replace a patient's damaged cells and thereby have the potential to 'cure' a disease and, in doing so, prevent or delay the onset of associated medical conditions. However, the cost of an expensive regenerative medicine and time to accrue any benefit linked to a decrease in co-morbidity expenditure may not outweigh the benefit for a healthcare community that has finite resources. The implications of this are discussed together with evidence that the UK National Institute for Health and Clinical Excellence (NICE) and the National Health Service (NHS) have established a precedent for a cost-sharing strategy with the pharmaceutical industry. PMID:21727138

  13. Pluripotent Stem Cells Models for Huntington's Disease: Prospects and Challenges

    Institute of Scientific and Technical Information of China (English)

    Richard L. Carter; Anthony W.S. Chan

    2012-01-01

    Pluripotent cellular models have shown great promise in the study of a number of neurological disorders.Several advantages of using a stem cell model include the potential for cells to derive disease relevant neuronal cell types,providing a system for researchers to monitor disease progression during neurogenesis,along with serving as a platform for drug discovery.A number of stem cell derived models have been employed to establish in vitro research models of Huntington's disease that can be used to investigate cellular pathology and screen for drug and cell-based therapies.Although some progress has been made,there are a number of challenges and limitations that must be overcome before the true potential of this research strategy is achieved,In this article we review current stem cell models that have been reported,as well as discuss the issues that impair these studies.We also highlight the prospective application of Huntington's disease stem cell models in the development of novel therapeutic strategies and advancement of personalized medicine.

  14. Using induced pluripotent stem cells as a tool for modellingcarcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Emma L Curry; Mohammad Moad; Craig N Robson; Rakesh Heer

    2015-01-01

    Cancer is a highly heterogeneous group of diseases thatdespite improved treatments remain prevalent accountingfor over 14 million new cases and 8.2 million deaths peryear. Studies into the process of carcinogenesis are limitedby lack of appropriate models for the development andpathogenesis of the disease based on human tissues.Primary culture of patient samples can help but is difficultto grow for a number of tissues. A potential opportunity toovercome these barriers is based on the landmark study byYamanaka which demonstrated the ability of four factors;Oct4, Sox2, Klf4, and c-Myc to reprogram human somaticcells in to pluripotency. These cells were termed inducedpluripotent stem cells (iPSCs) and display characteristicproperties of embryonic stem cells. This technique has awide range of potential uses including disease modelling,drug testing and transplantation studies. InterestinglyiPSCs also share a number of characteristics with cancercells including self-renewal and proliferation, expression ofstem cell markers and altered metabolism. Recently, iPSCshave been generated from a number of human cancercell lines and primary tumour samples from a range ofcancers in an attempt to recapitulate the developmentof cancer and interrogate the underlying mechanismsinvolved. This review will outline the similarities betweenthe reprogramming process and carcinogenesis, and howthese similarities have been exploited to generate iPSCmodels for a number of cancers.

  15. Modeling Rett Syndrome Using Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Andoh-Noda, Tomoko; Inouye, Michiko O; Miyake, Kunio; Kubota, Takeo; Okano, Hideyuki; Akamatsu, Wado

    2016-01-01

    Rett syndrome (RTT) is one of a group of neurodevelopmental disorders typically characterized by deficits in the X-linked gene MECP2 (methyl-CpG binding protein 2). The MECP2 gene encodes a multifunctional protein involved in transcriptional repression, transcriptional activation, chromatin remodeling, and RNA splicing. Genetic deletion of Mecp2 in mice revealed neuronal disabilities including RTT-like phenotypes and provided an excellent platform for understanding the pathogenesis of RTT. So far, there are no effective pharmacological treatments for RTT because the role of MECP2 in RTT is incompletely understood. Recently, human induced pluripotent stem cell (hiPSC) technologies have improved our knowledge of neurological and neurodevelopmental diseases including RTT because neurons derived from RTT-hiPSCs can be used for disease modeling to understand RTT phenotypes and to perform high throughput pharmaceutical drug screening. In this review, we provide an overview of RTT, including MeCP2 function and mouse models of RTT. In addition, we introduce recent advances in disease modeling of RTT using hiPSC-derived neural cells. PMID:27071793

  16. Induced Pluripotent Stem Cell Therapies for Cervical Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Vanessa M. Doulames

    2016-04-01

    Full Text Available Cervical-level injuries account for the majority of presented spinal cord injuries (SCIs to date. Despite the increase in survival rates due to emergency medicine improvements, overall quality of life remains poor, with patients facing variable deficits in respiratory and motor function. Therapies aiming to ameliorate symptoms and restore function, even partially, are urgently needed. Current therapeutic avenues in SCI seek to increase regenerative capacities through trophic and immunomodulatory factors, provide scaffolding to bridge the lesion site and promote regeneration of native axons, and to replace SCI-lost neurons and glia via intraspinal transplantation. Induced pluripotent stem cells (iPSCs are a clinically viable means to accomplish this; they have no major ethical barriers, sources can be patient-matched and collected using non-invasive methods. In addition, the patient’s own cells can be used to establish a starter population capable of producing multiple cell types. To date, there is only a limited pool of research examining iPSC-derived transplants in SCI—even less research that is specific to cervical injury. The purpose of the review herein is to explore both preclinical and clinical recent advances in iPSC therapies with a detailed focus on cervical spinal cord injury.

  17. Induced Pluripotent Stem Cell Therapies for Cervical Spinal Cord Injury.

    Science.gov (United States)

    Doulames, Vanessa M; Plant, Giles W

    2016-01-01

    Cervical-level injuries account for the majority of presented spinal cord injuries (SCIs) to date. Despite the increase in survival rates due to emergency medicine improvements, overall quality of life remains poor, with patients facing variable deficits in respiratory and motor function. Therapies aiming to ameliorate symptoms and restore function, even partially, are urgently needed. Current therapeutic avenues in SCI seek to increase regenerative capacities through trophic and immunomodulatory factors, provide scaffolding to bridge the lesion site and promote regeneration of native axons, and to replace SCI-lost neurons and glia via intraspinal transplantation. Induced pluripotent stem cells (iPSCs) are a clinically viable means to accomplish this; they have no major ethical barriers, sources can be patient-matched and collected using non-invasive methods. In addition, the patient's own cells can be used to establish a starter population capable of producing multiple cell types. To date, there is only a limited pool of research examining iPSC-derived transplants in SCI-even less research that is specific to cervical injury. The purpose of the review herein is to explore both preclinical and clinical recent advances in iPSC therapies with a detailed focus on cervical spinal cord injury. PMID:27070598

  18. Origination of the Protein Fold Repertoire from Oily Pluripotent Peptides

    Directory of Open Access Journals (Sweden)

    Ranjan V. Mannige

    2014-03-01

    Full Text Available While the repertoire of protein folds that exists today underlies most of life’s capabilities, our mechanistic picture of protein fold origination is incomplete. This paper discusses a hypothetical mechanism for the emergence of the protein fold repertoire from highly dynamic and collapsed peptides, exemplified by peptides with high oil content or hydrophobicity. These peptides are called pluripotent to emphasize their capacity to evolve into numerous folds transiently available to them. As evidence, the paper will discuss previous simulation work on the superior fold evolvability of oily peptides, trace (“fossil” evidence within proteomes seen today, and a general relationship between protein dynamism and evolvability. Aside from implications on the origination of protein folds, the hypothesis implies that the vanishing utility of a random peptide in protein origination may be relatively exaggerated, as some random peptides with a certain composition (e.g., oily may fare better than others. In later sections, the hypothesis is discussed in the context of existing discussions regarding the spontaneous origination of biomolecules.

  19. Induced pluripotent stem cells:origins, applications, and future perspectives

    Institute of Scientific and Technical Information of China (English)

    Jing ZHAO; Wen-jie JIANG; Chen SUN; Cong-zhe HOU; Xiao-mei YANG; Jian-gang GAO

    2013-01-01

    Embryonic stem (ES) cells are widely used for different purposes, including gene targeting, celltherapy, tissue repair, organ regeneration, and so on. However, studies and applications of ES cells are hindered by ethical issues regarding cellsources. To circumvent ethical disputes, great efforts have been taken to generate ES cel-like cells, which are not derived from the inner cellmass of blastocyst-stage embryos. In 2006, Yamanaka et al. first re-programmed mouse embryonic fibroblasts into ES cell-like cells cal ed induced pluripotent stem (iPS) cells. About one year later, Yamanaka et al. and Thomson et al. independently reprogrammed human somatic cells into iPS cells. Since the first generation of iPS cells, they have now been derived from quite a few different kinds of celltypes. In particular, the use of peripheral blood facilitates research on iPS cells because of safety, easy availability, and plenty of cellsources. Now iPS cells have been used for celltherapy, disease modeling, and drug discovery. In this review, we describe the generations, applications, potential issues, and future perspectives of iPS cells.

  20. Current progress and prospects of induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    CHEN LingYi; Liu Lin

    2009-01-01

    Induced pluripotent stem (iPS) cells are derived from somatic cells by ectopic expression of few transcription factors. Like embryonic stem (ES) cells, iPS cells are able to self-renew indefinitely and to differentiate into all types of cells in the body. iPS cells hold great promise for regenerative medicine,because iPS ceils circumvent not only immunological rejection but also ethical issues. Since the first report on the derivation of iPS cells in 2006, many laboratories all over the world started research on iPS cells and have made significant progress. This paper reviews recent progress in iPS cell research,Including the methods to generate iPS cells, the molecular mechanism of reprogramming in the formation of iPS ceils, and the potential applications of iPS cells in cell replacement therapy. Current problems that need to be addressed and the prospects for iPS research are also discussed.

  1. A new class of pluripotent stem cell cytotoxic small molecules.

    Directory of Open Access Journals (Sweden)

    Mark Richards

    Full Text Available A major concern in Pluripotent Stem Cell (PSC-derived cell replacement therapy is the risk of teratoma formation from contaminating undifferentiated cells. Removal of undifferentiated cells from differentiated cultures is an essential step before PSC-based cell therapies can be safely deployed in a clinical setting. We report a group of novel small molecules that are cytotoxic to PSCs. Our data indicates that these molecules are specific and potent in their activity allowing rapid eradication of undifferentiated cells. Experiments utilizing mixed PSC and primary human neuronal and cardiomyocyte cultures demonstrate that up to a 6-fold enrichment for specialized cells can be obtained without adversely affecting cell viability and function. Several structural variants were synthesized to identify key functional groups and to improve specificity and efficacy. Comparative microarray analysis and ensuing RNA knockdown studies revealed involvement of the PERK/ATF4/DDIT3 ER stress pathway. Surprisingly, cell death following ER stress induction was associated with a concomitant decrease in endogenous ROS levels in PSCs. Undifferentiated cells treated with these molecules preceding transplantation fail to form teratomas in SCID mice. Furthermore, these molecules remain non-toxic and non-teratogenic to zebrafish embryos suggesting that they may be safely used in vivo.

  2. Therapeutic opportunities: Telomere maintenance in inducible pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Gourronc, Francoise A. [Department of Microbiology, University of Iowa (United States); Klingelhutz, Aloysius J., E-mail: al-klingelhutz@uiowa.edu [Department of Microbiology, University of Iowa (United States)

    2012-02-01

    It has been demonstrated that exogenous expression of a combination of transcription factors can reprogram differentiated cells such as fibroblasts and keratinocytes into what have been termed induced pluripotent stem (iPS) cells. These iPS cells are capable of differentiating into all the tissue lineages when placed in the right environment and, in the case of mouse cells, can generate chimeric mice and be transmitted through the germline. Safer and more efficient methods of reprogramming are rapidly being developed. Clearly, iPS cells present a number of exciting possibilities, including disease modeling and therapy. A major question is whether the nuclei of iPS cells are truly rejuvenated or whether they might retain some of the marks of aging from the cells from which they were derived. One measure of cellular aging is the telomere. In this regard, recent studies have demonstrated that telomeres in iPS cells may be rejuvenated. They are not only elongated by reactivated telomerase but they are also epigenetically modified to be similar but not identical to embryonic stem cells. Upon differentiation, the derivative cells turn down telomerase, the telomeres begin to shorten again, and the telomeres and the genome are returned to an epigenetic state that is similar to normal differentiated somatic cells. While these preliminary telomere findings are promising, the overall genomic integrity of reprogrammed cells may still be problematic and further studies are needed to examine the safety and feasibility of using iPS cells in regenerative medicine applications.

  3. Proteomics and glycoproteomics of pluripotent stem-cell surface proteins.

    Science.gov (United States)

    Sun, Bingyun

    2015-03-01

    Pluripotent stem cells are a unique cell type with promising potential in regenerative and personalized medicine. Yet the difficulty to understand and coax their seemingly stochastic differentiation and spontaneous self-renewal have largely limited their clinical applications. A call has been made by numerous researchers for a better characterization of surface proteins on these cells, in search of biomarkers that can dictate developmental stages and lineage specifications, and can help formulate mechanistic insight of stem-cell fate choices. In the past two decades, proteomics has gained significant recognition in profiling surface proteins at high throughput. This review will summarize the impact of these studies on stem-cell biology, and discuss the used proteomic techniques. A systematic comparison of all the techniques and their results is also attempted here to help reveal pros, cons, and the complementarity of the existing methods. This awareness should assist in selecting suitable strategies for stem-cell related research, and shed light on technical improvements that can be explored in the future. PMID:25211708

  4. Current progress and prospects of induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Induced pluripotent stem(iPS) cells are derived from somatic cells by ectopic expression of few transcription factors.Like embryonic stem(ES) cells,iPS cells are able to self-renew indefinitely and to differentiate into all types of cells in the body.iPS cells hold great promise for regenerative medicine,because iPS cells circumvent not only immunological rejection but also ethical issues.Since the first report on the derivation of iPS cells in 2006,many laboratories all over the world started research on iPS cells and have made significant progress.This paper reviews recent progress in iPS cell research,including the methods to generate iPS cells,the molecular mechanism of reprogramming in the formation of iPS cells,and the potential applications of iPS cells in cell replacement therapy.Current problems that need to be addressed and the prospects for iPS research are also discussed.

  5. Modeling Neurological Disorders by Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Tanut Kunkanjanawan

    2011-01-01

    Full Text Available Studies of human brain development are critical as research on neurological disorders have been progressively advanced. However, understanding the process of neurogenesis through analysis of the early embryo is complicated and limited by a number of factors, including the complexity of the embryos, availability, and ethical constrains. The emerging of human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs has shed light of a new approach to study both early development and disease pathology. The cells behave as precursors of all embryonic lineages; thus, they allow tracing the history from the root to individual branches of the cell lineage tree. Systems for neural differentiation of hESCs and iPSCs have provided an experimental model that can be used to augment in vitro studies of in vivo brain development. Interestingly, iPSCs derived from patients, containing donor genetic background, have offered a breakthrough approach to study human genetics of neurodegenerative diseases. This paper summarizes the recent reports of the development of iPSCs from patients who suffer from neurological diseases and evaluates the feasibility of iPSCs as a disease model. The benefits and obstacles of iPSC technology are highlighted in order to raising the cautions of misinterpretation prior to further clinical translations.

  6. CTCF-Mediated Functional Chromatin Interactome in Pluripotent Cells

    Science.gov (United States)

    Handoko, Lusy; Xu, Han; Li, Guoliang; Ngan, Chew Yee; Chew, Elaine; Schnapp, Marie; Lee, Charlie Wah Heng; Ye, Chaopeng; Ping, Joanne Lim Hui; Mulawadi, Fabianus; Wong, Eleanor; Sheng, Jianpeng; Zhang, Yubo; Poh, Thompson; Chan, Chee Seng; Kunarso, Galih; Shahab, Atif; Bourque, Guillaume; Cacheux-Rataboul, Valere; Sung, Wing-Kin; Ruan, Yijun; Wei, Chia-Lin

    2011-01-01

    Mammalian genomes are viewed as functional organizations that orchestrate spatial and temporal gene regulation. CTCF, the most characterized insulator-binding protein, has been implicated as a key genome organizer. Yet, little is known about CTCF-associated higher order chromatin structures at a global scale. Here, we applied Chromatin Interaction Analysis by Paired-End-Tag sequencing to elucidate the CTCF-chromatin interactome in pluripotent cells. From this analysis, 1,480 cis and 336 trans interacting loci were identified with high reproducibility and precision. Associating these chromatin interaction loci with their underlying epigenetic states, promoter activities, enhancer binding and nuclear lamina occupancy, we uncovered five distinct chromatin domains that suggest potential new models of CTCF function in chromatin organization and transcriptional control. Specifically, CTCF interactions demarcate chromatin-nuclear membrane attachments and influence proper gene expression through extensive crosstalk between promoters and regulatory elements. This highly complex nuclear organization offers insights towards the unifying principles governing genome plasticity and function. PMID:21685913

  7. Therapeutic opportunities: Telomere maintenance in inducible pluripotent stem cells

    International Nuclear Information System (INIS)

    It has been demonstrated that exogenous expression of a combination of transcription factors can reprogram differentiated cells such as fibroblasts and keratinocytes into what have been termed induced pluripotent stem (iPS) cells. These iPS cells are capable of differentiating into all the tissue lineages when placed in the right environment and, in the case of mouse cells, can generate chimeric mice and be transmitted through the germline. Safer and more efficient methods of reprogramming are rapidly being developed. Clearly, iPS cells present a number of exciting possibilities, including disease modeling and therapy. A major question is whether the nuclei of iPS cells are truly rejuvenated or whether they might retain some of the marks of aging from the cells from which they were derived. One measure of cellular aging is the telomere. In this regard, recent studies have demonstrated that telomeres in iPS cells may be rejuvenated. They are not only elongated by reactivated telomerase but they are also epigenetically modified to be similar but not identical to embryonic stem cells. Upon differentiation, the derivative cells turn down telomerase, the telomeres begin to shorten again, and the telomeres and the genome are returned to an epigenetic state that is similar to normal differentiated somatic cells. While these preliminary telomere findings are promising, the overall genomic integrity of reprogrammed cells may still be problematic and further studies are needed to examine the safety and feasibility of using iPS cells in regenerative medicine applications.

  8. Retinal Organoids from Pluripotent Stem Cells Efficiently Recapitulate Retinogenesis.

    Science.gov (United States)

    Völkner, Manuela; Zschätzsch, Marlen; Rostovskaya, Maria; Overall, Rupert W; Busskamp, Volker; Anastassiadis, Konstantinos; Karl, Mike O

    2016-04-12

    The plasticity of pluripotent stem cells provides new possibilities for studying development, degeneration, and regeneration. Protocols for the differentiation of retinal organoids from embryonic stem cells have been developed, which either recapitulate complete eyecup morphogenesis or maximize photoreceptor genesis. Here, we have developed a protocol for the efficient generation of large, 3D-stratified retinal organoids that does not require evagination of optic-vesicle-like structures, which so far limited the organoid yield. Analysis of gene expression in individual organoids, cell birthdating, and interorganoid variation indicate efficient, reproducible, and temporally regulated retinogenesis. Comparative analysis of a transgenic reporter for PAX6, a master regulator of retinogenesis, shows expression in similar cell types in mouse in vivo, and in mouse and human retinal organoids. Early or late Notch signaling inhibition forces cell differentiation, generating organoids enriched with cone or rod photoreceptors, respectively, demonstrating the power of our improved organoid system for future research in stem cell biology and regenerative medicine. PMID:27050948

  9. Pluripotent stem cells: An in vitro model for nanotoxicity assessments.

    Science.gov (United States)

    Handral, Harish K; Tong, Huei Jinn; Islam, Intekhab; Sriram, Gopu; Rosa, Vinicus; Cao, Tong

    2016-10-01

    The advent of technology has led to an established range of engineered nanoparticles that are used in diverse applications, such as cell-cell interactions, cell-material interactions, medical therapies and the target modulation of cellular processes. The exponential increase in the utilization of nanomaterials and the growing number of associated criticisms has highlighted the potential risks of nanomaterials to human health and the ecosystem. The existing in vivo and in vitro platforms show limitations, with fluctuations being observed in the results of toxicity assessments. Pluripotent stem cells (PSCs) are viable source of cells that are capable of developing into specialized cells of the human body. PSCs can be efficiently used to screen new biomaterials/drugs and are potential candidates for studying impairments of biophysical morphology at both the cellular and tissue levels during interactions with nanomaterials and for diagnosing toxicity. Three-dimensional in vitro models obtained using PSC-derived cells would provide a realistic, patient-specific platform for toxicity assessments and in drug screening applications. The current review focuses on PSCs as an alternative in vitro platform for assessing the hazardous effects of nanomaterials on health systems and highlights the importance of PSC-derived in vitro platforms. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27241574

  10. Mimicking Retinal Development and Disease With Human Pluripotent Stem Cells.

    Science.gov (United States)

    Sinha, Divya; Phillips, Jenny; Joseph Phillips, M; Gamm, David M

    2016-04-01

    As applications of human pluripotent stem cells (hPSCs) continue to be refined and pursued, it is important to keep in mind that the strengths and weaknesses of this technology lie with its developmental origins. The remarkable capacity of differentiating hPSCs to recapitulate cell and tissue genesis has provided a model system to study stages of human development that were not previously amenable to investigation and experimentation. Furthermore, demonstration of developmentally appropriate, stepwise differentiation of hPSCs to specific cell types offers support for their authenticity and their suitability for use in disease modeling and cell replacement therapies. However, limitations to farming cells and tissues in an artificial culture environment, as well as the length of time required for most cells to mature, are some of the many issues to consider before using hPSCs to study or treat a particular disease. Given the overarching need to understand and modulate the dynamics of lineage-specific differentiation in stem cell cultures, this review will first examine the capacity of hPSCs to serve as models of retinal development. Thereafter, we will discuss efforts to model retinal disorders with hPSCs and present challenges that face investigators who aspire to use such systems to study disease pathophysiology and/or screen for therapeutics. We also refer readers to recent publications that provide additional insight and details on these rapidly evolving topics. PMID:27116663

  11. Germline Competent Pluripotent Mouse Stem Cells Generated by Plasmid Vectors.

    Science.gov (United States)

    Chen, Chien-Hong; Su, Yu-Hsiu; Lee, Kun-Hsiung; Chuang, Chin-Kai

    2016-07-01

    We developed nonintegrated methods to reprogram mouse embryonic fibroblast (MEF) cells into induced pluripotent stem cells (iPSCs) using pig pOct4, pSox2, and pc-Myc as well as human hKLF4, hAID, and hTDG that were carried by plasmid vectors. The 4F method employed pOct4, pSox2, pc-Myc, and hKLF4 to derive iPSC clones with naive embryonic stem cell (ESC)-like morphology. These 4F clones expressed endogenous mouse Nanog protein and could generate chimeras. In addition to the four conventional reprogramming factors used in the 4F method, hAID and hTDG were utilized in a 6F method to increase the conversion efficiency of reprogramming by approximately five-fold. One of the 6F plasmid derived iPSC (piPSC) clones was shown to be germline transmission competent. PMID:26980563

  12. Educating ecological architecture – ecological educational architecture

    OpenAIRE

    Costa Santos, Sandra; Klein, Gerald; Despang, Martin

    2010-01-01

    “Sustainability,” being the buzzword of the 21st century, is particularly challenging to the current generation, now in their early teens, which grew up with a childhood of lackadaisical use of fossil energy. This generation, which will soon be leading the world, has been inappropriately labeled the “generation me” and is expected to prove its successful transitioning into “generation p[ostfossil].” If the young emerging architectural professionals choose, they can be the mission group in hel...

  13. Virtual architecture: reconstructing architecture through photography

    OpenAIRE

    Germen, Murat

    2007-01-01

    The concept of construction in architectural design process is a temporary action that exists for a while and transforms itself into another product; i.e. the final building to be inhabited. Construction site can be taken as a podium where a play-to-remain-incomplete is being staged. The incompleteness causes us to dream, due to the fact that a complete building loses its narrative potential as it informs us about all the necessary pieces that constitute the whole: There is no puzzle to solve...

  14. Context-free pragmatism in Danish campus architecture

    DEFF Research Database (Denmark)

    Knudsen, Lars Emmerik Damgaard

    The idea of new pragmatism has inspired a new Danish wave in architecture that since 2012 has had enormous influence on the design of campus buildings in the professional education sector in Denmark. In arguing for a no-nonsense approach to architecture representatives of new pragmatism refers to...... reflects an educational ideal that also seem to lack a sense of context, and hence both the architecture and the educational structuring in Campus Roskilde can be understood as a context free pragmatism. I analyze this tendency with references to Dewey’s own work on the meaning of the educational...

  15. Perceived benefits from enterprise architecture

    OpenAIRE

    Plessius, Henk; Steenbergen, Marlies van; Slot, Raymond

    2014-01-01

    Enterprise Architecture has been developed in order to optimize the alignment between business needs and the (rapidly changing) possibilities of information technology. But do organizations indeed benefit from the application of Enterprise Architecture according to those who are in any way involved in architecture? To answer this question, a model has been developed (the Enterprise Architecture Value Framework) to organize the benefits of Enterprise Architecture. Based on this model, a survey...

  16. FASHION AND ARCHITECTURE

    Directory of Open Access Journals (Sweden)

    Hatice Harmankaya

    2014-04-01

    Full Text Available Fashion and architecture fields as non-verbal expression languages are affected by social, cultural, economic and historical factors and shaped around creativity. In both disciplines, based on human scales, employed material is brought dimension in the scope of math. Hue, texture, material, rate-ratio, line, form and shape are common design components of both fashion and architecture. Especially it is possible to see the accrued interactions in terms of pattern, form and decoration throughout the history. The aim of this survey is determining the common grounds, similarities, and interactions of clothing and architectural design that cover to protect the human body based on housing instinct. Descriptive method is used in the survey that examines the subject in depth. In the survey, that structural constitutions constructed on human body are studied in both fields in extent of art, status of fashion designers are affected from architecture is examined. New approaches are exhibited by giving examples of clothing designs in accordance with architectural principles.

  17. The Simulation Intranet Architecture

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, V.P.; Linebarger, J.M.; Miller, D.J.; Vandewart, R.L.

    1998-12-02

    The Simdarion Infranet (S1) is a term which is being used to dcscribc one element of a multidisciplinary distributed and distance computing initiative known as DisCom2 at Sandia National Laboratory (http ct al. 1998). The Simulation Intranet is an architecture for satisfying Sandia's long term goal of providing an end- to-end set of scrviccs for high fidelity full physics simu- lations in a high performance, distributed, and distance computing environment. The Intranet Architecture group was formed to apply current distributed object technologies to this problcm. For the hardware architec- tures and software models involved with the current simulation process, a CORBA-based architecture is best suited to meet Sandia's needs. This paper presents the initial desi-a and implementation of this Intranct based on a three-tier Network Computing Architecture(NCA). The major parts of the architecture include: the Web Cli- ent, the Business Objects, and Data Persistence.

  18. ZFPIP/Zfp462 is involved in P19 cell pluripotency and in their neuronal fate

    Energy Technology Data Exchange (ETDEWEB)

    Masse, Julie [CNRS UMR 6061, Institut de Genetique et Developpement de Rennes (IGDR), Rennes (France); Universite de Rennes 1, 35043 Rennes cedex (France); Piquet-Pellorce, Claire [Universite de Rennes 1, 35043 Rennes cedex, EA 4427 SeRAIC (France); Viet, Justine; Guerrier, Daniel; Pellerin, Isabelle [CNRS UMR 6061, Institut de Genetique et Developpement de Rennes (IGDR), Rennes (France); Universite de Rennes 1, 35043 Rennes cedex (France); Deschamps, Stephane, E-mail: stephane.deschamps@univ-rennes1.fr [CNRS UMR 6061, Institut de Genetique et Developpement de Rennes (IGDR), Rennes (France); Universite de Rennes 1, 35043 Rennes cedex (France)

    2011-08-01

    The nuclear zinc finger protein ZFPIP/Zfp462 is an important factor involved in cell division during the early embryonic development of vertebrates. In pluripotent P19 cells, ZFPIP/Zfp462 takes part in cell proliferation, likely via its role in maintaining chromatin structure. To further define the function of ZFPIP/Zfp462 in the mechanisms of pluripotency and cell differentiation, we constructed a stable P19 cell line in which ZFPIP/Zfp462 knockdown is inducible. We report that ZFPIP/Zfp462 was vital for mitosis and self-renewal in pluripotent P19 cells. Its depletion induced substantial decreases in the expression of the pluripotency genes Nanog, Oct4 and Sox2 and was associated with the transient expression of specific neuronal differentiation markers. We also demonstrated that ZFPIP/Zfp462 expression appears to be unnecessary after neuronal differentiation is induced in P19 cells. Taken together, our results strongly suggest that ZFPIP/Zfp462 is a key chromatin factor involved in maintaining P19 pluripotency and in the early mechanisms of neural differentiation but that it is dispensable in differentiated P19 cells.

  19. MicroRNAs and Induced Pluripotent Stem Cells for Human Disease Mouse Modeling

    Directory of Open Access Journals (Sweden)

    Chingiz Underbayev

    2012-01-01

    Full Text Available Human disease animal models are absolutely invaluable tools for our understanding of mechanisms involved in both physiological and pathological processes. By studying various genetic abnormalities in these organisms we can get a better insight into potential candidate genes responsible for human disease development. To this point a mouse represents one of the most used and convenient species for human disease modeling. Hundreds if not thousands of inbred, congenic, and transgenic mouse models have been created and are now extensively utilized in the research labs worldwide. Importantly, pluripotent stem cells play a significant role in developing new genetically engineered mice with the desired human disease-like phenotype. Induced pluripotent stem (iPS cells which represent reprogramming of somatic cells into pluripotent stem cells represent a significant advancement in research armament. The novel application of microRNA manipulation both in the generation of iPS cells and subsequent lineage-directed differentiation is discussed. Potential applications of induced pluripotent stem cell—a relatively new type of pluripotent stem cells—for human disease modeling by employing human iPS cells derived from normal and diseased somatic cells and iPS cells derived from mouse models of human disease may lead to uncovering of disease mechanisms and novel therapies.

  20. The role of telomeres and telomerase reverse transcriptase isoforms in pluripotency induction and maintenance.

    Science.gov (United States)

    Teichroeb, Jonathan H; Kim, Joohwan; Betts, Dean H

    2016-08-01

    Telomeres are linear guanine-rich DNA structures at the ends of chromosomes. The length of telomeric DNA is actively regulated by a number of mechanisms in highly proliferative cells such as germ cells, cancer cells, and pluripotent stem cells. Telomeric DNA is synthesized by way of the ribonucleoprotein called telomerase containing a reverse transcriptase (TERT) subunit and RNA component (TERC). TERT is highly conserved across species and ubiquitously present in their respective pluripotent cells. Recent studies have uncovered intricate associations between telomeres and the self-renewal and differentiation properties of pluripotent stem cells. Interestingly, the past decade's work indicates that the TERT subunit also has the capacity to modulate mitochondrial function, to remodel chromatin structure, and to participate in key signaling pathways such as the Wnt/β-catenin pathway. Many of these non-canonical functions do not require TERT's catalytic activity, which hints at possible functions for the extensive number of alternatively spliced TERT isoforms that are highly expressed in pluripotent stem cells. In this review, some of the established and potential routes of pluripotency induction and maintenance are highlighted from the perspectives of telomere maintenance, known TERT isoform functions and their complex regulation. PMID:26786236

  1. ZFPIP/Zfp462 is involved in P19 cell pluripotency and in their neuronal fate

    International Nuclear Information System (INIS)

    The nuclear zinc finger protein ZFPIP/Zfp462 is an important factor involved in cell division during the early embryonic development of vertebrates. In pluripotent P19 cells, ZFPIP/Zfp462 takes part in cell proliferation, likely via its role in maintaining chromatin structure. To further define the function of ZFPIP/Zfp462 in the mechanisms of pluripotency and cell differentiation, we constructed a stable P19 cell line in which ZFPIP/Zfp462 knockdown is inducible. We report that ZFPIP/Zfp462 was vital for mitosis and self-renewal in pluripotent P19 cells. Its depletion induced substantial decreases in the expression of the pluripotency genes Nanog, Oct4 and Sox2 and was associated with the transient expression of specific neuronal differentiation markers. We also demonstrated that ZFPIP/Zfp462 expression appears to be unnecessary after neuronal differentiation is induced in P19 cells. Taken together, our results strongly suggest that ZFPIP/Zfp462 is a key chromatin factor involved in maintaining P19 pluripotency and in the early mechanisms of neural differentiation but that it is dispensable in differentiated P19 cells.

  2. Nanog RNA-binding proteins YBX1 and ILF3 affect pluripotency of embryonic stem cells.

    Science.gov (United States)

    Guo, Chuanliang; Xue, Yan; Yang, Guanheng; Yin, Shang; Shi, Wansheng; Cheng, Yan; Yan, Xiaoshuang; Fan, Shuyue; Zhang, Huijun; Zeng, Fanyi

    2016-08-01

    Nanog is a well-known transcription factor that plays a fundamental role in stem cell self-renewal and the maintenance of their pluripotent cell identity. There remains a large data gap with respect to the spectrum of the key pluripotency transcription factors' interaction partners. Limited information is available concerning Nanog-associated RNA-binding proteins (RBPs), and the intrinsic protein-RNA interactions characteristic of the regulatory activities of Nanog. Herein, we used an improved affinity protocol to purify Nanog-interacting RBPs from mouse embryonic stem cells (ESCs), and 49 RBPs of Nanog were identified. Among them, the interaction of YBX1 and ILF3 with Nanog mRNA was further confirmed by in vitro assays, such as Western blot, RNA immunoprecipitation (RIP), and ex vivo methods, such as immunofluorescence staining and fluorescent in situ hybridization (FISH), MS2 in vivo biotin-tagged RNA affinity purification (MS2-BioTRAP). Interestingly, RNAi studies revealed that YBX1 and ILF3 positively affected the expression of Nanog and other pluripotency-related genes. Particularly, downregulation of YBX1 or ILF3 resulted in high expression of mesoderm markers. Thus, a reduction in the expression of YBX1 and ILF3 controls the expression of pluripotency-related genes in ESCs, suggesting their roles in further regulation of the pluripotent state of ESCs. PMID:26289635

  3. Theory of Traditional Chinese Aesthetic Thoughts Influence on Ancient Chinese Architectural Style

    Institute of Scientific and Technical Information of China (English)

    吴静

    2014-01-01

    the Chinese tradition of Confucianism, Taoism and Buddhism thought influence the design style of the building. Confu-cian, Taoist thought of"the doctrine of the mean"of"nature and humanity"ideology, traditional Confucian thought on the forma-tion of the traditional architectural style vital role. Of ancient Chinese architecture is harmonious and peaceful feelings, Confucian, Taoist, buddhist thought deeply, meanwhile, reflect the hand, reasonable aspiration is dependent of the aesthetic, the emotion affects the ancient Chinese architecture planning, layout and construction, formed the ancient Chinese architecture unique architectural style and artistic style and features.

  4. Software Architecture Design Reasoning

    Science.gov (United States)

    Tang, Antony; van Vliet, Hans

    Despite recent advancements in software architecture knowledge management and design rationale modeling, industrial practice is behind in adopting these methods. The lack of empirical proofs and the lack of a practical process that can be easily incorporated by practitioners are some of the hindrance for adoptions. In particular, the process to support systematic design reasoning is not available. To rectify this issue, we propose a design reasoning process to help architects cope with an architectural design environment where design concerns are cross-cutting and diversified.We use an industrial case study to validate that the design reasoning process can help improve the quality of software architecture design. The results have indicated that associating design concerns and identifying design options are important steps in design reasoning.

  5. Avionics System Architecture Tool

    Science.gov (United States)

    Chau, Savio; Hall, Ronald; Traylor, marcus; Whitfield, Adrian

    2005-01-01

    Avionics System Architecture Tool (ASAT) is a computer program intended for use during the avionics-system-architecture- design phase of the process of designing a spacecraft for a specific mission. ASAT enables simulation of the dynamics of the command-and-data-handling functions of the spacecraft avionics in the scenarios in which the spacecraft is expected to operate. ASAT is built upon I-Logix Statemate MAGNUM, providing a complement of dynamic system modeling tools, including a graphical user interface (GUI), modeling checking capabilities, and a simulation engine. ASAT augments this with a library of predefined avionics components and additional software to support building and analyzing avionics hardware architectures using these components.

  6. Persian architecture and mathematics

    CERN Document Server

    2012-01-01

    This volulme features eight original papers dedicated to the theme “Persian Architecture and Mathematics,” guest edited by Reza Sarhangi. All papers were approved through a rigorous process of blind peer review and edited by an interdisciplinary scientific editorial committee. Topics range from symmetry in ancient Persian architecture to the elaborate geometric patterns and complex three-dimensional structures of standing monuments of historical periods, from the expression of mathematical ideas to architectonic structures, and from decorative ornament to the representation of modern group theory and quasi-crystalline patterns. The articles discuss unique monuments Persia, including domed structures and two-dimensional patterns, which have received significant scholarly attention in recent years. This book is a unique contribution to studies of Persian architecture in relation to mathematics.

  7. Architecture of Environmental Engineering

    DEFF Research Database (Denmark)

    Wenzel, Henrik; Alting, Leo

    2006-01-01

    An architecture of Environmental Engineering has been developed comprising the various disciplines and tools involved. It identifies industry as the major actor and target group, and it builds on the concept of Eco-efficiency. To improve Eco-efficiency, there is a limited number of intervention......-efficiency is the aim of Environmental Engineering, the discipline of synthesis – design and creation of solutions – will form a core pillar of the architecture. Other disciplines of Environmental Engineering exist forming the necessary background and frame for the synthesis. Environmental Engineering, thus, in...... essence comprise the disciplines of: management, system description & inventory, analysis & assessment, prioritisation, synthesis, and communication, each existing at all levels of intervention. The developed architecture of Environmental Engineering, thus, consists of thirty individual disciplines...

  8. Architecture of Environmental Engineering

    DEFF Research Database (Denmark)

    Wenzel, Henrik; Alting, Leo

    2004-01-01

    An architecture of Environmental Engineering has been developed comprising the various disciplines and tools involved. It identifies industry as the major actor and target group, and it builds on the concept of Eco-efficiency. To improve Eco-efficiency, there is a limited number of intervention...... of Eco-efficiency is the aim of Environmental Engineering, the discipline of synthesis – design and creation of solutions – will form a core pillar of the architecture. Other disciplines of Environmental Engineering exist forming the necessary background and frame for the synthesis. Environmental...... Engineering, thus, in essence comprise the disciplines of: management, system description & inventory, analysis & assessment, prioritisation, synthesis, and communication, each existing at all levels of intervention. The developed architecture of Environmental Engineering, thus, consists of thirty individual...

  9. Expression of the pluripotency marker UTF1 is restricted to a subpopulation of early A spermatogonia in rat testis

    NARCIS (Netherlands)

    van Bragt, Maaike P. A.; Roepers-Gajadien, Hermien L.; Korver, Cindy M.; Bogerd, Jan; Okuda, Akihiko; Eggen, Bart J. L.; de Rooij, Dirk G.; van Pelt, Ans M. M.

    2008-01-01

    The population of early A spermatogonia includes stem cells that possess spermatogonial stern cell properties. Recent reports suggest that these cells have the ability to regain pluripotent properties. Here, we show that expression of the pluripotency marker undifferentiated embryonic cell transcrip

  10. Human testis-derived embryonic stem cell-like cells are not pluripotent, but possess potential of mesenchymal progenitors

    NARCIS (Netherlands)

    J.V. Chikhovskaya; M.J. Jonker; A. Meissner; T.M. Breit; S. Repping; A.M.M. van Pelt

    2012-01-01

    BACKGROUND Spontaneous in vitro transition of undifferentiated spermatogonia into the pluripotent cell state has been achieved using neonatal and adult mouse testis tissue. In an effort to establish an analogous source of human patient-specific pluripotent stem cells, several research groups have de

  11. Fluorescent Reporters in Human Pluripotent Stem Cells: Contributions to Cardiac Differentiation and Their Applications in Cardiac Disease and Toxicity

    NARCIS (Netherlands)

    Hartogh, den Sabine C.; Passier, Robert

    2016-01-01

    In the last decade, since the first report of induced pluripotent stem cells, the stem cell field has made remarkable progress in the differentiation to specialized cell-types of various tissues and organs, including the heart. Cardiac lineage- and tissue-specific human pluripotent stem cell (hPSC)

  12. Towards an Architectural Anthropology

    DEFF Research Database (Denmark)

    Stender, Marie

    2016-01-01

    Architecture and anthropology have always had overlapping interests regarding issues such as spatial organisation, forms of human dwellings and the interplay between social life and physical surroundings. Recent developments in both disciplines make it even more relevant to explore and evolve their...... overlaps and collaboration. However, there are also challenging differences to take into account regarding disciplinary traditions of e.g. communication, temporality and normativity. This article explores the potentials and challenges of architectural anthropology as a distinct sub-discipline, and outlines...

  13. Synergetics and architecture

    Science.gov (United States)

    Maslov, V. P.; Maslova, T. V.

    2008-03-01

    A series of phenomena pertaining to economics, quantum physics, language, literary criticism, and especially architecture is studied from the standpoint of synergetics (the study of self-organizing complex systems). It turns out that a whole series of concrete formulas describing these phenomena is identical in these different situations. This is the case of formulas relating to the Bose-Einstein distribution of particles and the distribution of words from a frequency dictionary. This also allows to apply a "quantized" from of the Zipf law to the problem of the authorship of Quiet Flows the Don and to the "blending in" of new architectural structures in an existing environment.

  14. Reframing information architecture

    CERN Document Server

    Resmini, Andrea

    2014-01-01

    Information architecture has changed dramatically since the mid-1990s and earlier conceptions of the world and the internet being different and separate have given way to a much more complex scenario in the present day. In the post-digital world that we now inhabit the digital and the physical blend easily and our activities and usage of information takes place through multiple contexts and via multiple devices and unstable, emergent choreographies. Information architecture now is steadily growing into a channel- or medium-specific multi-disciplinary framework, with contributions coming from a

  15. Interactive Architecture #1

    OpenAIRE

    Oosterhuis, K.; X. Xia

    2007-01-01

    The iA bookzine series will consist of twelve issues, bi-annually published over a period of six years under the supervision of Prof. ir. Kas Oosterhuis, director of the Hperbody at the Delft University of Technology. Interactive Architecture - from here on abbreviated as iA - is NOT simply architecture that is responsive or adaptive to changing circumstances. On the contrary, iA is based on the concept of bi-directional communication, which requires two active parties. Naturally, communicati...

  16. Radio-Communications Architectures

    OpenAIRE

    Diet, Antoine; Villegas, Martine; Baudoin, Genevieve; Robert, Fabien

    2010-01-01

    The goal of this chapter is to demonstrate the absolute need of matching the architecture design and the signal carrying the information. In section 1 and 2, considerations about current users' needs helped to identify three types of carrier signals in the context of radio-communications: NB-CW, WB-CW and IR. A separation between CW and IR signals is unavoidable because it drives us to a different technological design. Basic blocks of transmitter architecture are optimized in function with th...

  17. Information architecture. Volume 3: Guidance

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-04-01

    The purpose of this document, as presented in Volume 1, The Foundations, is to assist the Department of Energy (DOE) in developing and promulgating information architecture guidance. This guidance is aimed at increasing the development of information architecture as a Departmentwide management best practice. This document describes departmental information architecture principles and minimum design characteristics for systems and infrastructures within the DOE Information Architecture Conceptual Model, and establishes a Departmentwide standards-based architecture program. The publication of this document fulfills the commitment to address guiding principles, promote standard architectural practices, and provide technical guidance. This document guides the transition from the baseline or defacto Departmental architecture through approved information management program plans and budgets to the future vision architecture. This document also represents another major step toward establishing a well-organized, logical foundation for the DOE information architecture.

  18. Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells.

    Science.gov (United States)

    Patsch, Christoph; Challet-Meylan, Ludivine; Thoma, Eva C; Urich, Eduard; Heckel, Tobias; O'Sullivan, John F; Grainger, Stephanie J; Kapp, Friedrich G; Sun, Lin; Christensen, Klaus; Xia, Yulei; Florido, Mary H C; He, Wei; Pan, Wei; Prummer, Michael; Warren, Curtis R; Jakob-Roetne, Roland; Certa, Ulrich; Jagasia, Ravi; Freskgård, Per-Ola; Adatto, Isaac; Kling, Dorothee; Huang, Paul; Zon, Leonard I; Chaikof, Elliot L; Gerszten, Robert E; Graf, Martin; Iacone, Roberto; Cowan, Chad A

    2015-08-01

    The use of human pluripotent stem cells for in vitro disease modelling and clinical applications requires protocols that convert these cells into relevant adult cell types. Here, we report the rapid and efficient differentiation of human pluripotent stem cells into vascular endothelial and smooth muscle cells. We found that GSK3 inhibition and BMP4 treatment rapidly committed pluripotent cells to a mesodermal fate and subsequent exposure to VEGF-A or PDGF-BB resulted in the differentiation of either endothelial or vascular smooth muscle cells, respectively. Both protocols produced mature cells with efficiencies exceeding 80% within six days. On purification to 99% via surface markers, endothelial cells maintained their identity, as assessed by marker gene expression, and showed relevant in vitro and in vivo functionality. Global transcriptional and metabolomic analyses confirmed that the cells closely resembled their in vivo counterparts. Our results suggest that these cells could be used to faithfully model human disease. PMID:26214132

  19. Comprehensive characterization of genomic instability in pluripotent stem cells and their derived neuroprogenitor cell lines

    Directory of Open Access Journals (Sweden)

    Nestor Luis Lopez Corrales

    2012-12-01

    Full Text Available The genomic integrity of two human pluripotent stem cells and their derived neuroprogenitor cell lines was studied, applying a combination of high-resolution genetic methodologies. The usefulness of combining array-comparative genomic hybridization (aCGH and multiplex fluorescence in situ hybridization (M-FISH techniques should be delineated to exclude/detect a maximum of possible genomic structural aberrations. Interestingly, in parts different genomic imbalances at chromosomal and subchromosomal levels were detected in pluripotent stem cells and their derivatives. Some of the copy number variations were inherited from the original cell line, whereas other modifications were presumably acquired during the differentiation and manipulation procedures. These results underline the necessity to study both pluripotent stem cells and their differentiated progeny by as many approaches as possible in order to assess their genomic stability before using them in clinical therapies.

  20. Co-expression network analysis to identify pluripotency biomarkers in bovine and porcine embryos

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Freude, Karla Kristine; Hall, Vanessa Jane;

    stable culture of pluripotent cells in pig and cattle. Methods After quality control reads were pre-processed and mapped with STAR aligner. Post-mapping quality was checked with Qualimap. Finally the expression levels were estimated using HTSeq. Gene co-expression will be analyzed using a weighted...... network based method to identify highly co-expressed genes (module) and hub genes. Modules with a potential role in pluripotency will be identified with enrichment procedure and regulator genes identified with LemonTree algorithm. Differential wiring of modules among species will be evaluated. Expected...... results We expect to find out candidate pluripotency factors in porcine and bovine embryo. Acknowledgements We thank for the financial support from the EU project PluriSys, HEALTH-2007-B-223485....

  1. Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency.

    Science.gov (United States)

    Fiorenzano, Alessandro; Pascale, Emilia; D'Aniello, Cristina; Acampora, Dario; Bassalert, Cecilia; Russo, Francesco; Andolfi, Gennaro; Biffoni, Mauro; Francescangeli, Federica; Zeuner, Ann; Angelini, Claudia; Chazaud, Claire; Patriarca, Eduardo J; Fico, Annalisa; Minchiotti, Gabriella

    2016-01-01

    Known molecular determinants of developmental plasticity are mainly transcription factors, while the extrinsic regulation of this process has been largely unexplored. Here we identify Cripto as one of the earliest epiblast markers and a key extracellular determinant of the naive and primed pluripotent states. We demonstrate that Cripto sustains mouse embryonic stem cell (ESC) self-renewal by modulating Wnt/β-catenin, whereas it maintains mouse epiblast stem cell (EpiSC) and human ESC pluripotency through Nodal/Smad2. Moreover, we provide unprecedented evidence that Cripto controls the metabolic reprogramming in ESCs to EpiSC transition. Remarkably, Cripto deficiency attenuates ESC lineage restriction in vitro and in vivo, and permits ESC transdifferentiation into trophectoderm lineage, suggesting that Cripto has earlier functions than previously recognized. All together, our studies provide novel insights into the current model of mammalian pluripotency and contribute to the understanding of the extrinsic regulation of the first cell lineage decision in the embryo. PMID:27586544

  2. Multipotent (adult) and pluripotent stem cells for heart regeneration: what are the pros and cons?

    Science.gov (United States)

    Liao, Song-Yan; Tse, Hung-Fat

    2013-01-01

    Heart failure after myocardial infarction is the leading cause of mortality and morbidity worldwide. Existing medical and interventional therapies can only reduce the loss of cardiomyocytes during myocardial infarction but are unable to replenish the permanent loss of cardiomyocytes after the insult, which contributes to progressive pathological left ventricular remodeling and progressive heart failure. As a result, cell-based therapies using multipotent (adult) stem cells and pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells) have been explored as potential therapeutic approaches to restore cardiac function in heart failure. Nevertheless, the optimal cell type with the best therapeutic efficacy and safety for heart regeneration is still unknown. In this review, the potential pros and cons of different types of multipotent (adult) stem cells and pluripotent stem cells that have been investigated in preclinical and clinical studies are reviewed, and the future perspective of stem cell-based therapy for heart regeneration is discussed. PMID:24476362

  3. Induced pluripotent stem cells for retinal degenerative diseases: a new perspective on the challenges

    Indian Academy of Sciences (India)

    Zi-Bing Jin; Satoshi Okamoto; Michiko Mandai; Masayo Takahashi

    2009-12-01

    Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, are the prodominant causes of human blindness in the world; however, these diseases are difficult to treat. Currently, knowledge on the mechanisms of these diseases is still very limited and no radical drugs are available. Induced pluripotent stem (iPS) cells are an innovative technology that turns somatic cells into embryonic stem (ES)-like cells with pluripotent potential via the exogenous expression of several key genes. It can be used as an unlimited source for cell differentiation or tissue engineering, either of which is a promising therapy for human degenerative diseases. Induced pluripotent cells are both an unlimited source for retinal regeneration and an expectant tool for pharmaprojects and developmental or disease modelling. In this review, we try to summarize the advancement of iPS-based technologies and the potential utility for retinal degenerative diseases. We also discuss the challenges of using this technology in the retinology field.

  4. An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells.

    Science.gov (United States)

    Filareto, Antonio; Parker, Sarah; Darabi, Radbod; Borges, Luciene; Iacovino, Michelina; Schaaf, Tory; Mayerhofer, Timothy; Chamberlain, Jeffrey S; Ervasti, James M; McIvor, R Scott; Kyba, Michael; Perlingeiro, Rita C R

    2013-01-01

    Duchenne muscular dystrophy is a progressive and incurable neuromuscular disease caused by genetic and biochemical defects of the dystrophin-glycoprotein complex. Here we show the regenerative potential of myogenic progenitors derived from corrected dystrophic induced pluripotent stem cells generated from fibroblasts of mice lacking both dystrophin and utrophin. We correct the phenotype of dystrophic induced pluripotent stem cells using a Sleeping Beauty transposon system carrying the micro-utrophin gene, differentiate these cells into skeletal muscle progenitors and transplant them back into dystrophic mice. Engrafted muscles displayed large numbers of micro-utrophin-positive myofibers, with biochemically restored dystrophin-glycoprotein complex and improved contractile strength. The transplanted cells seed the satellite cell compartment, responded properly to injury and exhibit neuromuscular synapses. We also detect muscle engraftment after systemic delivery of these corrected progenitors. These results represent an important advance towards the future treatment of muscular dystrophies using genetically corrected autologous induced pluripotent stem cells. PMID:23462992

  5. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

    Directory of Open Access Journals (Sweden)

    Daniel R. Bayzigitov

    2016-01-01

    Full Text Available Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes.

  6. Genome editing of human pluripotent stem cells to generate human cellular disease models

    Directory of Open Access Journals (Sweden)

    Kiran Musunuru

    2013-07-01

    Full Text Available Disease modeling with human pluripotent stem cells has come into the public spotlight with the awarding of the Nobel Prize in Physiology or Medicine for 2012 to Drs John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. This discovery has opened the door for the generation of pluripotent stem cells from individuals with disease and the differentiation of these cells into somatic cell types for the study of disease pathophysiology. The emergence of genome-editing technology over the past few years has made it feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Here, recent technological advances in genome editing, and its utility in human biology and disease studies, are reviewed.

  7. Pluripotency factor binding and Tsix expression act synergistically to repress Xist in undifferentiated embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Nesterova Tatyana B

    2011-10-01

    Full Text Available Abstract Background Expression of Xist, the master regulator of X chromosome inactivation, is extinguished in pluripotent cells, a process that has been linked to programmed X chromosome reactivation. The key pluripotency transcription factors Nanog, Oct4 and Sox2 are implicated in Xist gene extinction, at least in part through binding to an element located in Xist intron 1. Other pathways, notably repression by the antisense RNA Tsix, may also be involved. Results Here we employ a transgene strategy to test the role of the intron 1 element and Tsix in repressing Xist in ES cells. We find that deletion of the intron 1 element causes a small increase in Xist expression and that simultaneous deletion of the antisense regulator Tsix enhances this effect. Conclusion We conclude that Tsix and pluripotency factors act synergistically to repress Xist in undifferentiated embryonic stem cells. Double mutants do not exhibit maximal levels of Xist expression, indicating that other pathways also play a role.

  8. Derivation of Neural Progenitors and Retinal Pigment Epithelium from Common Marmoset and Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Laughing Bear Torrez

    2012-01-01

    Full Text Available Embryonic and induced pluripotent stem cells (IPSCs derived from mammalian species are valuable tools for modeling human disease, including retinal degenerative eye diseases that result in visual loss. Restoration of vision has focused on transplantation of neural progenitor cells (NPCs and retinal pigmented epithelium (RPE to the retina. Here we used transgenic common marmoset (Callithrix jacchus and human pluripotent stem cells carrying the enhanced green fluorescent protein (eGFP reporter as a model system for retinal differentiation. Using suspension and subsequent adherent differentiation cultures, we observed spontaneous in vitro differentiation that included NPCs and cells with pigment granules characteristic of differentiated RPE. Retinal cells derived from human and common marmoset pluripotent stem cells provide potentially unlimited cell sources for testing safety and immune compatibility following autologous or allogeneic transplantation using nonhuman primates in early translational applications.

  9. Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells.

    Science.gov (United States)

    Siller, Richard; Greenhough, Sebastian; Naumovska, Elena; Sullivan, Gareth J

    2015-05-12

    The differentiation of pluripotent stem cells to hepatocytes is well established, yet current methods suffer from several drawbacks. These include a lack of definition and reproducibility, which in part stems from continued reliance on recombinant growth factors. This has remained a stumbling block for the translation of the technology into industry and the clinic for reasons associated with cost and quality. We have devised a growth-factor-free protocol that relies on small molecules to differentiate human pluripotent stem cells toward a hepatic phenotype. The procedure can efficiently direct both human embryonic stem cells and induced pluripotent stem cells to hepatocyte-like cells. The final population of cells demonstrates marker expression at the transcriptional and protein levels, as well as key hepatic functions such as serum protein production, glycogen storage, and cytochrome P450 activity. PMID:25937370

  10. A qPCR ScoreCard quantifies the differentiation potential of human pluripotent stem cells.

    Science.gov (United States)

    Tsankov, Alexander M; Akopian, Veronika; Pop, Ramona; Chetty, Sundari; Gifford, Casey A; Daheron, Laurence; Tsankova, Nadejda M; Meissner, Alexander

    2015-11-01

    Research on human pluripotent stem cells has been hampered by the lack of a standardized, quantitative, scalable assay of pluripotency. We previously described an assay called ScoreCard that used gene expression signatures to quantify differentiation efficiency. Here we report an improved version of the assay based on qPCR that enables faster, more quantitative assessment of functional pluripotency. We provide an in-depth characterization of the revised signature panel (commercially available as the TaqMan hPSC Scorecard Assay) through embryoid body and directed differentiation experiments as well as a detailed comparison to the teratoma assay. We further show that the improved ScoreCard enables a wider range of applications, such as screening of small molecules, genetic perturbations and assessment of culture conditions. Our approach can be extended beyond stem cell applications to characterize and assess the utility of other cell types and lineages. PMID:26501952

  11. An improved ScoreCard to assess the differentiation potential of human pluripotent stem cells

    Science.gov (United States)

    Tsankov, Alexander M.; Akopian, Veronika; Pop, Ramona; Chetty, Sundari; Gifford, Casey A.; Daheron, Laurence; Melton, Douglas A.; Tsankova, Nadejda M.; Meissner, Alexander

    2015-01-01

    Research on human pluripotent stem cells has been hampered by the lack of a standardized, quantitative, scalable assay of pluripotency. We have previously described an assay called ScoreCard that used gene expression signatures to quantify differentiation efficiency. Here we report an improved version of the assay based on qPCR that enables faster, more quantitative assessment of functional pluripotency. We provide an in-depth characterization of the revised signature panel through embryoid body and directed differentiation experiments as well as a detailed comparison to the teratoma assay. We also show that the improved ScoreCard enables applications such as screening of small molecules, genetic perturbations and assessment of culture conditions. Beyond stem cell applications, this approach can in principle be extended to other cell types and lineages. PMID:26501952

  12. The L1TD1 Protein Interactome Reveals the Importance of Post-transcriptional Regulation in Human Pluripotency

    Directory of Open Access Journals (Sweden)

    Maheswara Reddy Emani

    2015-03-01

    Full Text Available The RNA-binding protein L1TD1 is one of the most specific and abundant proteins in pluripotent stem cells and is essential for the maintenance of pluripotency in human cells. Here, we identify the protein interaction network of L1TD1 in human embryonic stem cells (hESCs and provide insights into the interactome network constructed in human pluripotent cells. Our data reveal that L1TD1 has an important role in RNA splicing, translation, protein traffic, and degradation. L1TD1 interacts with multiple stem-cell-specific proteins, many of which are still uncharacterized in the context of development. Further, we show that L1TD1 is a part of the pluripotency interactome network of OCT4, SOX2, and NANOG, bridging nuclear and cytoplasmic regulation and highlighting the importance of RNA biology in pluripotency.

  13. Biomedical laboratories: architecture and radioprotection principles

    International Nuclear Information System (INIS)

    In institutions where biological research are made and some technologies make use of radioisotope, the radiation protection is an issue of biosecurity for conceptual reasons. In the process of architectural design of Biomedical Laboratories, engineering and architecture reveal interfaces with other areas of knowledge and specific concepts. Exploring the role of architectural design in favor of personal and environmental protection in biological containment laboratories that handle non-sealed sources in research, the work discusses the triad that compose the principle of containment in health environments: best practices, protective equipment, physical facilities, with greater emphasis on the latter component. The shortcomings of the design process are reflected in construction and in use-operation and maintenance of these buildings, with direct consequences on the occupational health and safety, environmental and credibility of work processes. In this context, the importance of adoption of alternatives to improve the design process is confirmed, taking into account the early consideration of several variables involved and providing subsidies to the related laboratories . The research, conducted at FIOCRUZ - a Brazilian health institution, developed from the analysis of the participants in the architectural project, aiming at the formulation of design guidelines which could contribute to the rationalisation of this kind of building construction

  14. Discrete optimization in architecture architectural & urban layout

    CERN Document Server

    Zawidzki, Machi

    2016-01-01

    This book presents three projects that demonstrate the fundamental problems of architectural design and urban composition – the layout design, evaluation and optimization. Part I describes the functional layout design of a residential building, and an evaluation of the quality of a town square (plaza). The algorithm for the functional layout design is based on backtracking using a constraint satisfaction approach combined with coarse grid discretization. The algorithm for the town square evaluation is based on geometrical properties derived directly from its plan. Part II introduces a crowd-simulation application for the analysis of escape routes on floor plans, and optimization of a floor plan for smooth crowd flow. The algorithms presented employ agent-based modeling and cellular automata.

  15. Hadl: HUMS Architectural Description Language

    Science.gov (United States)

    Mukkamala, R.; Adavi, V.; Agarwal, N.; Gullapalli, S.; Kumar, P.; Sundaram, P.

    2004-01-01

    Specification of architectures is an important prerequisite for evaluation of architectures. With the increase m the growth of health usage and monitoring systems (HUMS) in commercial and military domains, the need far the design and evaluation of HUMS architectures has also been on the increase. In this paper, we describe HADL, HUMS Architectural Description Language, that we have designed for this purpose. In particular, we describe the features of the language, illustrate them with examples, and show how we use it in designing domain-specific HUMS architectures. A companion paper contains details on our design methodology of HUMS architectures.

  16. Energy metabolism in human pluripotent stem cells and their differentiated counterparts.

    Directory of Open Access Journals (Sweden)

    Sandra Varum

    Full Text Available Human pluripotent stem cells have the ability to generate all cell types present in the adult organism, therefore harboring great potential for the in vitro study of differentiation and for the development of cell-based therapies. Nonetheless their use may prove challenging as incomplete differentiation of these cells might lead to tumoregenicity. Interestingly, many cancer types have been reported to display metabolic modifications with features that might be similar to stem cells. Understanding the metabolic properties of human pluripotent stem cells when compared to their differentiated counterparts can thus be of crucial importance. Furthermore recent data has stressed distinct features of different human pluripotent cells lines, namely when comparing embryo-derived human embryonic stem cells (hESCs and induced pluripotent stem cells (IPSCs reprogrammed from somatic cells.We compared the energy metabolism of hESCs, IPSCs, and their somatic counterparts. Focusing on mitochondria, we tracked organelle localization and morphology. Furthermore we performed gene expression analysis of several pathways related to the glucose metabolism, including glycolysis, the pentose phosphate pathway and the tricarboxylic acid (TCA cycle. In addition we determined oxygen consumption rates (OCR using a metabolic extracellular flux analyzer, as well as total intracellular ATP levels by high performance liquid chromatography (HPLC. Finally we explored the expression of key proteins involved in the regulation of glucose metabolism.Our results demonstrate that, although the metabolic signature of IPSCs is not identical to that of hESCs, nonetheless they cluster with hESCs rather than with their somatic counterparts. ATP levels, lactate production and OCR revealed that human pluripotent cells rely mostly on glycolysis to meet their energy demands. Furthermore, our work points to some of the strategies which human pluripotent stem cells may use to maintain high

  17. Generation of induced pluripotent stem cells from domestic goats.

    Science.gov (United States)

    Sandmaier, Shelley E S; Nandal, Anjali; Powell, Anne; Garrett, Wesley; Blomberg, Leann; Donovan, David M; Talbot, Neil; Telugu, Bhanu P

    2015-09-01

    The creation of genetically modified goats provides a powerful approach for improving animal health, enhancing production traits, animal pharming, and for ensuring food safety all of which are high-priority goals for animal agriculture. The availability of goat embryonic stem cells (ESCs) that are characteristically immortal in culture would be of enormous benefit for developing genetically modified animals. As an alternative to long-sought goat ESCs, we generated induced pluripotent stem cells (iPSC) by forced expression of bovine POU5F1, SOX2, MYC, KLF4, LIN-28, and NANOG reprogramming factors in combination with a MIR302/367 cluster, delivered by lentiviral vectors. In order to minimize integrations, the reprogramming factor coding sequences were assembled with porcine teschovirus-1 2A (P2A) self-cleaving peptides that allowed for tri-cistronic expression from each vector. The lentiviral-transduced cells were cultured on irradiated mouse feeder cells in a semi-defined, serum-free medium containing fibroblast growth factor (FGF) and/or leukemia inhibitory factor (LIF). The resulting goat iPSC exhibit cell and colony morphology typical of human and mouse ESCs-that is, well-defined borders, a high nuclear-to-cytoplasmic ratio, a short cell-cycle interval, alkaline phosphatase expression, and the ability to generate teratomas in vivo. Additionally, these goat iPSC demonstrated the ability to differentiate into directed lineages in vitro. These results constitute the first steps in establishing integration and footprint-free iPSC from ruminants. Mol. Reprod. Dev. 82: 709-721, 2015. © 2015 Wiley Periodicals, Inc. PMID:26118622

  18. Trophoblast lineage cells derived from human induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying, E-mail: ying.chen@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Wang, Kai; Chandramouli, Gadisetti V.R. [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Knott, Jason G. [Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University (United States); Leach, Richard, E-mail: Richard.leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group (United States)

    2013-07-12

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.

  19. Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells.

    Science.gov (United States)

    Grow, Edward J; Flynn, Ryan A; Chavez, Shawn L; Bayless, Nicholas L; Wossidlo, Mark; Wesche, Daniel J; Martin, Lance; Ware, Carol B; Blish, Catherine A; Chang, Howard Y; Pera, Renee A Reijo; Wysocka, Joanna

    2015-06-11

    Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections, and comprise nearly 8% of the human genome. The most recently acquired human ERV is HERVK(HML-2), which repeatedly infected the primate lineage both before and after the divergence of the human and chimpanzee common ancestor. Unlike most other human ERVs, HERVK retained multiple copies of intact open reading frames encoding retroviral proteins. However, HERVK is transcriptionally silenced by the host, with the exception of in certain pathological contexts such as germ-cell tumours, melanoma or human immunodeficiency virus (HIV) infection. Here we demonstrate that DNA hypomethylation at long terminal repeat elements representing the most recent genomic integrations, together with transactivation by OCT4 (also known as POU5F1), synergistically facilitate HERVK expression. Consequently, HERVK is transcribed during normal human embryogenesis, beginning with embryonic genome activation at the eight-cell stage, continuing through the emergence of epiblast cells in preimplantation blastocysts, and ceasing during human embryonic stem cell derivation from blastocyst outgrowths. Remarkably, we detected HERVK viral-like particles and Gag proteins in human blastocysts, indicating that early human development proceeds in the presence of retroviral products. We further show that overexpression of one such product, the HERVK accessory protein Rec, in a pluripotent cell line is sufficient to increase IFITM1 levels on the cell surface and inhibit viral infection, suggesting at least one mechanism through which HERVK can induce viral restriction pathways in early embryonic cells. Moreover, Rec directly binds a subset of cellular RNAs and modulates their ribosome occupancy, indicating that complex interactions between retroviral proteins and host factors can fine-tune pathways of early human development. PMID:25896322

  20. Trophoblast lineage cells derived from human induced pluripotent stem cells

    International Nuclear Information System (INIS)

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro

  1. Architecture Descriptions. A Contribution to Modeling of Production System Architecture

    DEFF Research Database (Denmark)

    Jepsen, Allan Dam; Hvam, Lars

    operational design and handling of production system architecture, research is conducted into the description of production system architecture, including what an architecture description contains in general and what it should describe for production systems specifically. The contribution in this area of...... research consists of three parts. First, a conceptual model of architecture descriptions is established based on the ISO/IEC/IEEE 42010 standard. Secondly, the stakeholders and architecture related concerns of relevance for descriptions of production system architectures are investigated, and requirements......The subject of this PhD dissertation is architecture-centric design and the description of production system architecture. Companies are facing demands for the development and production of new products at an ever increasing rate, as the market life of products decreases and the rate at which...

  2. American School & University Architectural Portfolio 2000 Awards: Landscape Architecture.

    Science.gov (United States)

    American School & University, 2000

    2000-01-01

    Presents photographs and basic information on architectural design, costs, square footage, and principle designers of the award winning school landscaping projects that competed in the American School & University Architectural Portfolio 2000. (GR)

  3. Graduate transfer exam (DGS and architecture program: Example of Selcuk University, department of architecture

    Directory of Open Access Journals (Sweden)

    Mehmet Uysal

    2011-02-01

    offered. Another program that is not compatible with undergraduate architecture education is vocational program of Restoration and Conservation. Vocational program in “Construction Draft” provides the best match for and is mostly compatible with architecture education. This program offers courses pertaining to four different fields of architecture. Due to the distribution pattern of the vocational programs, both quantitative and qualitative problems are observed in view of teaching staff and curriculum. The adaptation period which is precisely deliberated under law needs to be extended for architecture and similar academic fields. It has been observed that those students transferred to Selcuk University, Department of Architecture through DGS face many problems of academic achievement in design related courses due to the lack of design courses in their previous academic disciplines, the short duration of adaptation period, and the inability to compensate for the lack of design education in such short periods. Although these students manage to complete their undergraduate education, they suffer the lack of design education especially during the earlier semesters and generally become insufficient in reflecting the understanding of architectural design. ConclusionIt is an undisputed fact that vocational and technical education and training is important for Turkey. The present and planned regulations point at an increasing number of students to be admitted to two-year degree programs and even more students admitted to undergraduate programs in different fields. Hence, the education of transfer students through DGS becomes more and more important. Evaluating the present situation and programs of vocational training, it is recommended that further Construction Draft Departments shall be opened and transfers from these departments should be encouraged. Restoration departments might be converted to architectural restoration departments considering the quantity and quality of

  4. Robustness via Diffractal Architectures

    CERN Document Server

    Moocarme, Matthew

    2015-01-01

    When plane waves diffract through fractal-patterned apertures, the resulting far-field profiles or diffractals also exhibit iterated, self-similar features. Here we show that this specific architecture enables robust signal processing and spatial multiplexing: arbitrary parts of a diffractal contain sufficient information to recreate the entire original sparse signal.

  5. Embedded instrumentation systems architecture

    Science.gov (United States)

    Visnevski, Nikita A.

    2007-04-01

    This paper describes the operational concept of the Embedded Instrumentation Systems Architecture (EISA) that is being developed for Test and Evaluation (T&E) applications. The architecture addresses such future T&E requirements as interoperability, flexibility, and non-intrusiveness. These are the ultimate requirements that support continuous T&E objectives. In this paper, we demonstrate that these objectives can be met by decoupling the Embedded Instrumentation (EI) system into an on-board and an off-board component. An on-board component is responsible for sampling, pre-processing, buffering, and transmitting data to the off-board component. The latter is responsible for aggregating, post-processing, and storing test data as well as providing access to the data via a clearly defined interface including such aspects as security, user authentication and access control. The power of the EISA architecture approach is in its inherent ability to support virtual instrumentation as well as enabling interoperability with such important T&E systems as Integrated Network-Enhanced Telemetry (iNET), Test and Training Enabling Architecture (TENA) and other relevant Department of Defense initiatives.

  6. Sun, space and architecture

    Energy Technology Data Exchange (ETDEWEB)

    Iyama, Takeshi

    1987-01-01

    Several projects being performed in Japan on the relationship between architectural space and solar energy are briefly described. The experimental buildings under investigation include the Matsumoto house, the Maruyama house, a tropical dome, the Teraoka Windhouse restaurant, a cross-cultural building blueprint, the Hirata town hall blueprint, the Kijo Alumni hall plan and the 'Ever-Spring' house.

  7. Architectural workshop Tyre3

    OpenAIRE

    Vasa J. Perović; Aljoša Dekleva; Anja Vidic

    2012-01-01

    The workshop deals with and researches three topics: space, user and material. The topics are developed in a parallel and mutually interrelated way, with the final intention being to undertake an architectural intervention on 1:1 scale within a specific public space for a specific user.

  8. Robotically Driven Architectural Production

    OpenAIRE

    Bier, H.H.

    2014-01-01

    Robotically driven architectural production advances seamless, computer-numerically controlled (CNC) and robotically supported design to production and operation processes enabling im-plementation of robotically driven buildings from conceptualisation to use. It enables production of free-formed, heterogeneous, optimized structures in order to address specific requirements in terms of properties (density, consistency, rigidity, etc.) and behaviours (re-configurability, responsiveness, etc.) i...

  9. Architecture Sauvage

    DEFF Research Database (Denmark)

    Baumeister, Ruth

    Danish artist Asger Jorn (1914-1973) is internationally renowed as a proponent of Nordic art and for his activities as a member of Cobra and the Situationist International. Quite apart from his art, Jorn produced a remarkable quantity of writing on art, architecture and urbanism and engaged in...

  10. Enterprise Architecture Evaluation

    DEFF Research Database (Denmark)

    Andersen, Peter; Carugati, Andrea

    2014-01-01

    By being holistically preoccupied with coherency among organizational elements such as organizational strategy, business needs and the IT functions role in supporting the business, enterprise architecture (EA) has grown to become a core competitive advantage. Though EA is a maturing research area...

  11. Future Network Architectures

    DEFF Research Database (Denmark)

    Wessing, Henrik; Bozorgebrahimi, Kurosh; Belter, Bartosz;

    2015-01-01

    This study identifies key requirements for NRENs towards future network architectures that become apparent as users become more mobile and have increased expectations in terms of availability of data. In addition, cost saving requirements call for federated use of, in particular, the optical...

  12. Drawing Music, Playing Architecture

    OpenAIRE

    Makrinos, George Adam

    2005-01-01

    ARCHITECTURE AND MUSIC SHARE INTRINSIC MEANINGS GENERATED BY A CONSTANT STREAM OF METAPHORS WHICH ARE FORMS OF POETIC TRANSFORMATIONS. This thesis sought to challange the present way an architect-musician makes drawings through the exploration of multimedia possibilities at hand. The drawings are composed using Macromedia Flash MX. OPEN HOMEPAGE.EXE To download flash player, click here: Download flash Player

  13. Architecture, constraints, and behavior

    OpenAIRE

    Doyle, John C.; Csete, Marie

    2011-01-01

    This paper aims to bridge progress in neuroscience involving sophisticated quantitative analysis of behavior, including the use of robust control, with other relevant conceptual and theoretical frameworks from systems engineering, systems biology, and mathematics. Familiar and accessible case studies are used to illustrate concepts of robustness, organization, and architecture (modularity and protocols) that are central to understanding complex networks. These essential organizational feature...

  14. Architecture and Energy

    DEFF Research Database (Denmark)

    Lauring, Michael; Marsh, Rob

    2009-01-01

    , and where the transition from an industrial to an information- or knowledge-based society is well-developed. The last three decades of the 20th century show many conscientious - both governmental and architectural - Danish attempts at creating buildings with lower heat consumption. The lower U...

  15. Architectural Creation of Light

    DEFF Research Database (Denmark)

    Bülow, Katja

    2015-01-01

    Bidraget "Architectural Creation of Light" indgår sammen med 108 andre bidrag i bogen "You Say Light, I Think Shadow". Bogens indhold undersøger: "Hvad er lys". I dette bidrag besvares spørgsmålet gennem iagttagelser af arkitektstuderendes undersøgelser af lyset i deres arbejdsmodeller i...

  16. Smart Grid Architectures

    DEFF Research Database (Denmark)

    Dondossola, Giovanna; Terruggia, Roberta; Bessler, Sandford;

    2014-01-01

    The scope of this paper is to address the evolution of distribution grid architectures following the widespread introduction of renewable energy sources. The increasing connection of distributed resources has a strong impact on the topology and the control functionality of the current distribution...

  17. Enterprise Architecture (EA) Roadmap

    Data.gov (United States)

    Office of Personnel Management — The Enterprise Roadmap reflects the information technology (IT) investment priorities established in agency PortfolioStat reviews, as well as IT program decisions...

  18. Programming and Reprogramming Cellular Age in the Era of Induced Pluripotency.

    Science.gov (United States)

    Studer, Lorenz; Vera, Elsa; Cornacchia, Daniela

    2015-06-01

    The ability to reprogram adult somatic cells back to pluripotency presents a powerful tool for studying cell-fate identity and modeling human disease. However, the reversal of cellular age during reprogramming results in an embryonic-like state of induced pluripotent stem cells (iPSCs) and their derivatives, which presents specific challenges for modeling late onset disease. This age reset requires novel methods to mimic age-related changes but also offers opportunities for studying cellular rejuvenation in real time. Here, we discuss how iPSC research may transform studies of aging and enable the precise programming of cellular age in parallel to cell-fate specification. PMID:26046759

  19. Differentiate or Die: 3-Bromopyruvate and Pluripotency in Mouse Embryonic Stem Cells.

    Directory of Open Access Journals (Sweden)

    Ana Sofia Rodrigues

    Full Text Available Pluripotent embryonic stem cells grown under standard conditions (ESC have a markedly glycolytic profile, which is shared with many different types of cancer cells. Thus, some therapeutic strategies suggest that pharmacologically shifting cancer cells towards an oxidative phenotype, using glycolysis inhibitors, may reduce cancer aggressiveness. Given the metabolic parallels between cancer and stemness would chemotherapeutical agents have an effect on pluripotency, and could a strategy involving these agents be envisioned to modulate stem cell fate in an accessible manner? In this manuscript we attempted to determine the effects of 3-bromopyruvate (3BrP in pluripotency. Although it has other intracellular targets, this compound is a potent inhibitor of glycolysis enzymes thought to be important to maintain a glycolytic profile. The goal was also to determine if we could contribute towards a pharmacologically accessible metabolic strategy to influence cell differentiation.Mouse embryonic stem cells (mESC grown under standard pluripotency conditions (in the presence of Leukemia Inducing Factor- LIF were treated with 3BrP. As a positive control for differentiation other mESCs were grown without LIF. Overall our results demonstrate that 3BrP negatively affects pluripotency, forcing cells to become less glycolytic and with more active mitochondria. These changes in metabolism are correlated with increased differentiation, even under pluripotency conditions (i.e. in the presence of LIF. However, 3BrP also significantly impaired cell function, and may have other roles besides affecting the metabolic profile of mESCs.Treatment of mESCs with 3BrP triggered a metabolic switch and loss of pluripotency, even in the presence of LIF. Interestingly, the positive control for differentiation allowed for a distinction between 3BrP effects and changes associated with spontaneous differentiation/loss of pluripotency in the absence of LIF. Additionally, there was a

  20. Brf1 posttranscriptionally regulates pluripotency and differentiation responses downstream of Erk MAP kinase

    OpenAIRE

    Tan, Frederick E.; Elowitz, Michael B.

    2014-01-01

    AU-rich element mRNA-binding proteins (AUBPs) are key regulators of development, but how they are controlled and what functional roles they play depends on cellular context. Here, we show that Brf1 (zfp36l1), an AUBP from the Zfp36 protein family, operates downstream of FGF/Erk MAP kinase signaling to regulate pluripotency and cell fate decision making in mouse embryonic stem cells (mESCs). FGF/Erk MAP kinase signaling up-regulates Brf1, which disrupts the expression of core pluripotency-asso...

  1. Architecture of Institution & Home. Architecture as Cultural Medium

    OpenAIRE

    Robinson, J W

    2004-01-01

    This dissertation addresses how architecture functions as a cultural medium. It does so by by investigating how the architecture of institution and home each construct and support different cultural practices. By studying the design of ordinary settings in terms of how qualitative differences in architectural environments affect those who use them, this study exemplifies architectural research directed toward constructive cultural change. In the United States, ordinary people often describe h...

  2. Geometric Rationalization for Freeform Architecture

    KAUST Repository

    jiang, caigui

    2016-06-20

    The emergence of freeform architecture provides interesting geometric challenges with regards to the design and manufacturing of large-scale structures. To design these architectural structures, we have to consider two types of constraints. First, aesthetic constraints are important because the buildings have to be visually impressive. Sec- ond, functional constraints are important for the performance of a building and its e cient construction. This thesis contributes to the area of architectural geometry. Specifically, we are interested in the geometric rationalization of freeform architec- ture with the goal of combining aesthetic and functional constraints and construction requirements. Aesthetic requirements typically come from designers and architects. To obtain visually pleasing structures, they favor smoothness of the building shape, but also smoothness of the visible patterns on the surface. Functional requirements typically come from the engineers involved in the construction process. For exam- ple, covering freeform structures using planar panels is much cheaper than using non-planar ones. Further, constructed buildings have to be stable and should not collapse. In this thesis, we explore the geometric rationalization of freeform archi- tecture using four specific example problems inspired by real life applications. We achieve our results by developing optimization algorithms and a theoretical study of the underlying geometrical structure of the problems. The four example problems are the following: (1) The design of shading and lighting systems which are torsion-free structures with planar beams based on quad meshes. They satisfy the functionality requirements of preventing light from going inside a building as shad- ing systems or reflecting light into a building as lighting systems. (2) The Design of freeform honeycomb structures that are constructed based on hex-dominant meshes with a planar beam mounted along each edge. The beams intersect without

  3. Urban planning, architecture, landscape architecture projects underway for Roanoke

    OpenAIRE

    Chadwick, Heather Riley

    2009-01-01

    Faculty and students in the College of Architecture and Urban Studies at Virginia Tech bring expertise and solutions to communities all around the world. Currently, the college is working on six different urban planning, architecture, and landscape architecture projects in Roanoke, Va.

  4. ACOUSTICS IN ARCHITECTURAL DESIGN, AN ANNOTATED BIBLIOGRAPHY ON ARCHITECTURAL ACOUSTICS.

    Science.gov (United States)

    DOELLE, LESLIE L.

    THE PURPOSE OF THIS ANNOTATED BIBLIOGRAPHY ON ARCHITECTURAL ACOUSTICS WAS--(1) TO COMPILE A CLASSIFIED BIBLIOGRAPHY, INCLUDING MOST OF THOSE PUBLICATIONS ON ARCHITECTURAL ACOUSTICS, PUBLISHED IN ENGLISH, FRENCH, AND GERMAN WHICH CAN SUPPLY A USEFUL AND UP-TO-DATE SOURCE OF INFORMATION FOR THOSE ENCOUNTERING ANY ARCHITECTURAL-ACOUSTIC DESIGN…

  5. Enterprise architecture evaluation using architecture framework and UML stereotypes

    OpenAIRE

    Narges Shahi; Ali Haroun Abadi; Hadi abooei mehrizi

    2014-01-01

    There is an increasing need for enterprise architecture in numerous organizations with complicated systems with various processes. Support for information technology, organizational units whose elements maintain complex relationships increases. Enterprise architecture is so effective that its non-use in organizations is regarded as their institutional inability in efficient information technology management. The enterprise architecture process generally consists of three phases including stra...

  6. A Communication Architecture For IVHS

    OpenAIRE

    Streisand, Susan L.; Walrand, Jean

    1992-01-01

    This paper documents the development of a communications architecture for Intelligent Vehicle Highway Systems (IVHS) being studied by the California PATH Program. The authors use a layered architecture based on the OSI 7- layer reference model.

  7. An Experiment in Architectural Instruction.

    Science.gov (United States)

    Dvorak, Robert W.

    1978-01-01

    Discusses the application of the PLATO IV computer-based educational system to a one-semester basic drawing course for freshman architecture, landscape architecture, and interior design students and relates student reactions to the experience. (RAO)

  8. Makers of Architecture

    DEFF Research Database (Denmark)

    Ayres, Phil

    One of five critical essays discussing and reflecting upon the design, fabrication and construction of a folded steel structure for Kielder forest, Northumberland, UK......One of five critical essays discussing and reflecting upon the design, fabrication and construction of a folded steel structure for Kielder forest, Northumberland, UK...

  9. Economics-driven software architecture

    CERN Document Server

    Mistrik, Ivan; Kazman, Rick; Zhang, Yuanyuan

    2014-01-01

    Economics-driven Software Architecture presents a guide for engineers and architects who need to understand the economic impact of architecture design decisions: the long term and strategic viability, cost-effectiveness, and sustainability of applications and systems. Economics-driven software development can increase quality, productivity, and profitability, but comprehensive knowledge is needed to understand the architectural challenges involved in dealing with the development of large, architecturally challenging systems in an economic way. This book covers how to apply economic consider

  10. Controlling Material Reactivity Using Architecture.

    Science.gov (United States)

    Sullivan, Kyle T; Zhu, Cheng; Duoss, Eric B; Gash, Alexander E; Kolesky, David B; Kuntz, Joshua D; Lewis, Jennifer A; Spadaccini, Christopher M

    2016-03-01

    3D-printing methods are used to generate reactive material architectures. Several geometric parameters are observed to influence the resultant flame propagation velocity, indicating that the architecture can be utilized to control reactivity. Two different architectures, channels and hurdles, are generated, and thin films of thermite are deposited onto the surface. The architecture offers an additional route to control, at will, the energy release rate in reactive composite materials. PMID:26669517

  11. Compositional Specification of Software Architecture

    Science.gov (United States)

    Penix, John; Lau, Sonie (Technical Monitor)

    1998-01-01

    This paper describes our experience using parameterized algebraic specifications to model properties of software architectures. The goal is to model the decomposition of requirements independent of the style used to implement the architecture. We begin by providing an overview of the role of architecture specification in software development. We then describe how architecture specifications are build up from component and connector specifications and give an overview of insights gained from a case study used to validate the method.

  12. Enterprise architecture for business success

    CERN Document Server

    Wijegunaratne, Inji; Evans-Greenwood, Peter

    2014-01-01

    Enterprise Architecture (EA) has evolved to become a prominent presence in today's information systems and technology landscape. The EA discipline is rich in frameworks, methodologies, and the like. However, the question of 'value' for business ;professionals remains largely unanswered - that is, how best can Enterprise Architecture and Enterprise Architects deliver value to the enterprise? Enterprise Architecture for Business Success answers this question. Enterprise Architecture for Business Success is primarily intended for IT professionals working in the area of Enterprise Architectu

  13. Architectural Design Activities for JAS

    CERN Document Server

    Khaled, Lena

    2009-01-01

    The critical part for building any software system is its architecture. Architectural design is a design at a higher level of abstraction. A good architecture ensures that software will satisfy its requirement. This paper defines the most important activities of architectural design that used through building any software; also it applies these activities on one type of Electronic Commerce (EC) applications that is Job Agency System(JAS) to show how these activities can work through these types of applications.

  14. Software, architecture, and participatory design

    OpenAIRE

    Rank, Stephen; O'Coill, Carl; Boldyreff, Cornelia; Doughty, Mark

    2004-01-01

    Much work in software architecture has been inspired by work in physical architecture, in particular Alexander's work on `design patterns'. By contrast, Alexander's work is little-used in town planning and architecture. In this paper, we examine some of the reasons that this is so, describe some parallels and differences between the fields of physical and software architecture, and identify areas in which future collaboration may be fruitful. The notion of `participatory design' is important ...

  15. Architecture for autonomy

    Science.gov (United States)

    Broten, Gregory S.; Monckton, Simon P.; Collier, Jack; Giesbrecht, Jared

    2006-05-01

    In 2002 Defence R&D Canada changed research direction from pure tele-operated land vehicles to general autonomy for land, air, and sea craft. The unique constraints of the military environment coupled with the complexity of autonomous systems drove DRDC to carefully plan a research and development infrastructure that would provide state of the art tools without restricting research scope. DRDC's long term objectives for its autonomy program address disparate unmanned ground vehicle (UGV), unattended ground sensor (UGS), air (UAV), and subsea and surface (UUV and USV) vehicles operating together with minimal human oversight. Individually, these systems will range in complexity from simple reconnaissance mini-UAVs streaming video to sophisticated autonomous combat UGVs exploiting embedded and remote sensing. Together, these systems can provide low risk, long endurance, battlefield services assuming they can communicate and cooperate with manned and unmanned systems. A key enabling technology for this new research is a software architecture capable of meeting both DRDC's current and future requirements. DRDC built upon recent advances in the computing science field while developing its software architecture know as the Architecture for Autonomy (AFA). Although a well established practice in computing science, frameworks have only recently entered common use by unmanned vehicles. For industry and government, the complexity, cost, and time to re-implement stable systems often exceeds the perceived benefits of adopting a modern software infrastructure. Thus, most persevere with legacy software, adapting and modifying software when and wherever possible or necessary -- adopting strategic software frameworks only when no justifiable legacy exists. Conversely, academic programs with short one or two year projects frequently exploit strategic software frameworks but with little enduring impact. The open-source movement radically changes this picture. Academic frameworks

  16. Architectural engineering of FRP bridges

    OpenAIRE

    Smits, J.E.P.

    2014-01-01

    This paper deals with the use of Fibre Reinforced Polymers (FRP's) in architectural and structural bridge design. The challenges and opportunities that come with this relatively new material are discussed. An inventory is made of recent engineers' solutions in FRP, followed by a discussion on architectural application of FRP's derived from the authors architectural practice.

  17. Communication of IT-Architecture

    NARCIS (Netherlands)

    Koning, H.

    2008-01-01

    This PhD thesis contains the results of various research activities that fall under the topic ‘communication of IT-architecture’. The term IT-architecture defines the various types of architecture that can be found in the domain of Information Technology (software architecture, enterprise architectu

  18. Meet French Architecture in China

    Institute of Scientific and Technical Information of China (English)

    Susan

    2005-01-01

    On April 5, a French architectural exhibition entitled ""French Visions: City, Architecture and Sustainable Development"" was unveiled in Beijing Urban Planning Center. As a key exhibition within the framework of French Year in China, the exhibition will also be displayed in Shanghai and Chongqing. The largest exhibition of its kind ever held in China, French Visions extensively showed accomplishments of contemporary French architectural design.

  19. Orientations to Reflective Practice.

    Science.gov (United States)

    Wellington, Bud; Austin, Patricia

    1996-01-01

    Delineates five orientations to reflective practice: immediate, technical, deliberative, dialectic, and transpersonal, each reflecting different social science bases and beliefs and values about education. Views them as interactive, interdependent, noncompeting, aspects of reflective practice. (SK)

  20. Collagen-graft mixed cellulose esters membrane maintains undifferentiated morphology and markers of potential pluripotency in feeder-free culture of induced pluripotent stem cells.

    Science.gov (United States)

    Lotfalah Moradi, Sadegh; Hajishafieeha, Zahra; Nojedehi, Shahrzad; Dinarvand, Vida; Hesami Tackallou, Saeed; Roy, Ram V; Ardeshirylajimi, Abdolreza; Soleimani, Masoud

    2016-09-01

    Induced pluripotent stem cells (iPSCs) are unique and unlimited clinical sources of stem cell therapy for the regenerative medicine. Feeder layer preparation is an important step for iPSCs production, which is expensive, time-consuming and requires conversance. In the present study, we investigated the maintenance of pluripotency, and stemness of the iPSCs through feeder-free culture on a collagen-grafted Mixed Cellulose Esters membrane (MCE-COL) after three passages during twelve days. Results have demonstrated that the iPSCs cultured on MCE-COL membrane had a fine, typical undifferentiated morphology, increased proliferation rate and significant multi-lineage differentiation potential. Alkaline phosphatase (ALP) staining and pluripotency associated gene markers expression further confirmed that iPSCs cultured on the surface of MCE-COL had more ALP positive colonies and enhanced expression of Oct-4, Nanog, Sox-2 and ALP in comparison with MCE and control groups. Since MCE-COL membrane has three dimensional structure and bioactivity, it has the potential for usage in the feeder-free culture of iPSCs, and could be a suitable candidate to use as a feeder layer in stem cells preparation. PMID:27449919

  1. Architecture in metamorphosis

    Directory of Open Access Journals (Sweden)

    Tomas Ghisellini

    2015-11-01

    Full Text Available In this “dromocractic” era, dominated by the absolute values of speed and short duration of each phenomenon, architecture is called to the paradoxical challenge of precariousness, which is actually transient and fleeting. In a delicate combinational process between freedom and construction, lightness and gravity, the tool for contemporary urban design, can only be that which governs the near future of our cities. The process of exchange between architecture and design has to deal primarily with the multidisciplinary character that has been influencing creative professions which have increasingly more in common with one another. The figure of the designer has taken on characters, skills and roles that were unthinkable until recently times. Failing to understand this transformation will condemn the designer as irrelevant.

  2. Generic robot architecture

    Science.gov (United States)

    Bruemmer, David J [Idaho Falls, ID; Few, Douglas A [Idaho Falls, ID

    2010-09-21

    The present invention provides methods, computer readable media, and apparatuses for a generic robot architecture providing a framework that is easily portable to a variety of robot platforms and is configured to provide hardware abstractions, abstractions for generic robot attributes, environment abstractions, and robot behaviors. The generic robot architecture includes a hardware abstraction level and a robot abstraction level. The hardware abstraction level is configured for developing hardware abstractions that define, monitor, and control hardware modules available on a robot platform. The robot abstraction level is configured for defining robot attributes and provides a software framework for building robot behaviors from the robot attributes. Each of the robot attributes includes hardware information from at least one hardware abstraction. In addition, each robot attribute is configured to substantially isolate the robot behaviors from the at least one hardware abstraction.

  3. Heterogeneous network architectures

    DEFF Research Database (Denmark)

    Christiansen, Henrik Lehrmann

    2006-01-01

    Future networks will be heterogeneous! Due to the sheer size of networks (e.g., the Internet) upgrades cannot be instantaneous and thus heterogeneity appears. This means that instead of trying to find the olution, networks hould be designed as being heterogeneous. One of the key equirements here...... is flexibility. This thesis investigates such heterogeneous network architectures and how to make them flexible. A survey of algorithms for network design is presented, and it is described how using heuristics can increase the speed. A hierarchical, MPLS based network architecture is described...... and it is discussed that it is advantageous to heterogeneous networks and illustrated by a number of examples. Modeling and simulation is a well-known way of doing performance evaluation. An approach to event-driven simulation of communication networks is presented and mixed complexity modeling, which can simplify...

  4. Consistent model driven architecture

    Science.gov (United States)

    Niepostyn, Stanisław J.

    2015-09-01

    The goal of the MDA is to produce software systems from abstract models in a way where human interaction is restricted to a minimum. These abstract models are based on the UML language. However, the semantics of UML models is defined in a natural language. Subsequently the verification of consistency of these diagrams is needed in order to identify errors in requirements at the early stage of the development process. The verification of consistency is difficult due to a semi-formal nature of UML diagrams. We propose automatic verification of consistency of the series of UML diagrams originating from abstract models implemented with our consistency rules. This Consistent Model Driven Architecture approach enables us to generate automatically complete workflow applications from consistent and complete models developed from abstract models (e.g. Business Context Diagram). Therefore, our method can be used to check practicability (feasibility) of software architecture models.

  5. Architecture and communication

    Directory of Open Access Journals (Sweden)

    Špela Hudnik

    2003-01-01

    Full Text Available The article presents effects of technology, science and capital strategies on changes in traditional forms and definitions of space, architecture and bodies. It confronts us with new processes of thinking and living that are constantly being transformed into new dynamic time and spatial contexts. Space is becoming the information filter, communication network. A cross-section of three landscapes: landscape of megastructures, nomadic landscapes and psychedelic landscapes, theory contributes to understanding of media and space-age technology, information technology and electronical language. It offers designs of various megastructures, media surfaces and envelopes of contemporary information society: the anthropological module, hyper- and infra-bodies, bio-electronical bodies and population genetics bodies. It presents the architecture of communication.

  6. Dance Architecture Spatiality

    OpenAIRE

    Renard, Johanna

    2014-01-01

    L’ouvrage rassemble les traces visuelles et textuelles du programme intensif européen DAS (Dance Architecture Spatiality), coordonné par Frédérique Villemur, qui s’est déroulé en 2012 à Athènes, sur les collines face à l’Acropole. Guidés par Patrice Barthès, chorégraphe en résidence à l’ENSAM de Montpellier, une vingtaine d’étudiants en architecture, esthétique et design ont explorés les interactions entre le geste dansé et les temporalités architecturales et paysagères. Accueilli par l’Isado...

  7. Constructing Active Architectures in the ArchWare ADL

    CERN Document Server

    Morrison, Ron; Balasubramaniam, Dharini; Mickan, Kath; Oquendo, Flavio; Cîmpan, Sorana; Warboys, Brian; Snowdon, Bob; Greenwood, Mark

    2010-01-01

    Software that cannot change is condemned to atrophy: it cannot accommodate the constant revision and re-negotiation of its business goals nor intercept the potential of new technology. To accommodate change in such systems we have defined an active software architecture to be: dynamic in that the structure and cardinality of the components and interactions are not statically known; updatable in that components can be replaced dynamically; and evolvable in that it permits its executing specification to be changed. Here we describe the facilities of the ArchWare architecture description language (ADL) for specifying active architectures. The contribution of the work is the unique combination of concepts including: a {\\pi}-calculus based communication and expression language for specifying executable architectures; hyper-code as an underlying representation of system execution; a decomposition operator to break up and introspect on executing systems; and structural reflection for creating new components and bind...

  8. An event-based architecture for solving constraint satisfaction problems

    Science.gov (United States)

    Mostafa, Hesham; Müller, Lorenz K.; Indiveri, Giacomo

    2015-12-01

    Constraint satisfaction problems are ubiquitous in many domains. They are typically solved using conventional digital computing architectures that do not reflect the distributed nature of many of these problems, and are thus ill-suited for solving them. Here we present a parallel analogue/digital hardware architecture specifically designed to solve such problems. We cast constraint satisfaction problems as networks of stereotyped nodes that communicate using digital pulses, or events. Each node contains an oscillator implemented using analogue circuits. The non-repeating phase relations among the oscillators drive the exploration of the solution space. We show that this hardware architecture can yield state-of-the-art performance on random SAT problems under reasonable assumptions on the implementation. We present measurements from a prototype electronic chip to demonstrate that a physical implementation of the proposed architecture is robust to practical non-idealities and to validate the theory proposed.

  9. Handling Variability in Software Architecture : Problems and Implications

    NARCIS (Netherlands)

    Galster, Matthias; Avgeriou, Paris

    2011-01-01

    Variability helps manage differences and commonalities within and across software systems. As variability is reflected in and facilitated through the software architecture, it is important to understand the problems that architects face when carrying out their tasks. This would help us improve metho

  10. Specific lectin biomarkers for isolation of human pluripotent stem cells identified through array-based glycomic analysis

    Institute of Scientific and Technical Information of China (English)

    Yu-Chieh Wang; Trevor R Leonardo; Ying Liu; Suzanne E Peterson; Louise C Laurent; Shinya Yamanaka; Jeanne F Loring; Masato Nakagawa; Ibon Garitaonandia; Ileana Slavin; Gulsah Altun; Robert M Lacharite; Kristopher L Nazor; Ha T Tran; Candace L Lynch

    2011-01-01

    Rapid and dependable methods for isolating human pluripotent stem cell (hPSC) populations are urgently needed for quality control in basic research and in cell-based therapy applications.Using lectin arrays,we analyzed glycoproteins extracted from 26 hPSC samples and 22 differentiated cell samples,and identified a small group of iectins with distinctive binding signatures that were sufficient to distinguish hPSCs from a variety of non-pluripotent cell types.These specific biomarkers were shared by all the 12 human embryonic stem cell and the 14 human induced pluripotent stem cell samples examined,regardless of the laboratory of origin,the culture conditions,the somatic cell type reprogrammed,or the reprogramming method used.We demonstrated a practical application of specific lectin binding by detecting hPSCs within a differentiated cell population with lectin-mediated staining followed by fluorescence microscopy and flow cytometry,and by enriching and purging viable hPSCs from mixed cell populations using lectin-mediated cell separation.Global gene expression analysis showed pluripotency-associated differential expression of specific fucosyltransferases and sialyltransferases,which may underlie these differences in protein glycosylation and lectin binding.Taken together,our results show that protein glycosylation differs considerably between pluripotent and non-pluripotent cells,and demonstrate that lectins may be used as biomarkers to monitor pluripotency in stem cell populations and for removal of viable hPSCs from mixed cell populations.

  11. Architecture and communication

    OpenAIRE

    Špela Hudnik

    2003-01-01

    The article presents effects of technology, science and capital strategies on changes in traditional forms and definitions of space, architecture and bodies. It confronts us with new processes of thinking and living that are constantly being transformed into new dynamic time and spatial contexts. Space is becoming the information filter, communication network. A cross-section of three landscapes: landscape of megastructures, nomadic landscapes and psychedelic landscapes, theory contributes to...

  12. An Embodied Architecture

    OpenAIRE

    Frances Downing; Upali Nanda; Narongpon Laiprakobsup; Shima B. Mohajeri

    2012-01-01

    An architecture of the body is emerging out of theories of biology, complexity, and systems through the use of an evolving organism as its metaphor. Autopoiesis is the term used by biologists to describe the realm of existence for a living organism as it slides between the interchange of structure and information. Incoming information is filtered through the organism for its usefulness in the art of staying alive. Structural or organizational changes evolve as the organism adjusts to new info...

  13. Avionics Architecture Modelling Language

    Science.gov (United States)

    Alana, Elena; Naranjo, Hector; Valencia, Raul; Medina, Alberto; Honvault, Christophe; Rugina, Ana; Panunzia, Marco; Dellandrea, Brice; Garcia, Gerald

    2014-08-01

    This paper presents the ESA AAML (Avionics Architecture Modelling Language) study, which aimed at advancing the avionics engineering practices towards a model-based approach by (i) identifying and prioritising the avionics-relevant analyses, (ii) specifying the modelling language features necessary to support the identified analyses, and (iii) recommending/prototyping software tooling to demonstrate the automation of the selected analyses based on a modelling language and compliant with the defined specification.

  14. Conservation of Architectural Heritage

    OpenAIRE

    Quintero, mario Santana; Blake, Bill; Eppich, Rand

    2007-01-01

    Currently, a wide range of digital sensors for capturing our architectural heritage are available. They offer the opportunity to acquire large sets of information in a relatively short time. These sensors include digital photography (photogrammetry-scaled rectified photography), total stations, laser scanners, high-resolution panoramic devices, etc. A lot of effort has been put in the application of these tools in the field of conservation, however a significant gap exists between the informa...

  15. Information systems definition architecture

    Energy Technology Data Exchange (ETDEWEB)

    Calapristi, A.J.

    1996-06-20

    The Tank Waste Remediation System (TWRS) Information Systems Definition architecture evaluated information Management (IM) processes in several key organizations. The intent of the study is to identify improvements in TWRS IM processes that will enable better support to the TWRS mission, and accommodate changes in TWRS business environment. The ultimate goals of the study are to reduce IM costs, Manage the configuration of TWRS IM elements, and improve IM-related process performance.

  16. Aerobot Autonomy Architecture

    Science.gov (United States)

    Elfes, Alberto; Hall, Jeffery L.; Kulczycki, Eric A.; Cameron, Jonathan M.; Morfopoulos, Arin C.; Clouse, Daniel S.; Montgomery, James F.; Ansar, Adnan I.; Machuzak, Richard J.

    2009-01-01

    An architecture for autonomous operation of an aerobot (i.e., a robotic blimp) to be used in scientific exploration of planets and moons in the Solar system with an atmosphere (such as Titan and Venus) is undergoing development. This architecture is also applicable to autonomous airships that could be flown in the terrestrial atmosphere for scientific exploration, military reconnaissance and surveillance, and as radio-communication relay stations in disaster areas. The architecture was conceived to satisfy requirements to perform the following functions: a) Vehicle safing, that is, ensuring the integrity of the aerobot during its entire mission, including during extended communication blackouts. b) Accurate and robust autonomous flight control during operation in diverse modes, including launch, deployment of scientific instruments, long traverses, hovering or station-keeping, and maneuvers for touch-and-go surface sampling. c) Mapping and self-localization in the absence of a global positioning system. d) Advanced recognition of hazards and targets in conjunction with tracking of, and visual servoing toward, targets, all to enable the aerobot to detect and avoid atmospheric and topographic hazards and to identify, home in on, and hover over predefined terrain features or other targets of scientific interest. The architecture is an integrated combination of systems for accurate and robust vehicle and flight trajectory control; estimation of the state of the aerobot; perception-based detection and avoidance of hazards; monitoring of the integrity and functionality ("health") of the aerobot; reflexive safing actions; multi-modal localization and mapping; autonomous planning and execution of scientific observations; and long-range planning and monitoring of the mission of the aerobot. The prototype JPL aerobot (see figure) has been tested extensively in various areas in the California Mojave desert.

  17. From science to architecture

    OpenAIRE

    Coleman, Honor

    2014-01-01

    non-peer-reviewed My thesis began with an interest in finding various differences and commonalities in the fields of science and architecture. I have always been interested by the seemingly fast paced progression of science and technology in comparison to other creative fields. There appears to be a constant stream of discoveries and new technologies. And so I wondered if there was anything about the way the scientist works that the architect could learn. I began by reading books abo...

  18. Attacks on Emerging Architectures

    OpenAIRE

    Hanna, Steven Craig

    2012-01-01

    New architectures require careful examination of security properties in order to assess and contain new threats. In light of this, emerging technologies, such as web APIs, medical devices, and applications on mobile phones, are a new security landscape that has recurring security problems. We develop new techniques to analyze these applications for security vulnerabilities, utilizing techniques including: dynamic symbolic execution, binary analysis and reverse engineering, and wide scale appl...

  19. A Natural Language Architecture

    OpenAIRE

    Sodiya, Adesina Simon

    2007-01-01

    Natural languages are the latest generation of programming languages, which require processing real human natural expressions. Over the years, several groups or researchers have trying to develop widely accepted natural language languages based on artificial intelligence (AI). But no true natural language has been developed. The goal of this work is to design a natural language preprocessing architecture that identifies and accepts programming instructions or sentences in their natural forms ...

  20. Software Architecture in Depth

    OpenAIRE

    Lars Heinemann; Christian Neumann; Birgit Penzenstadler; Wassiou Sitou

    2016-01-01

    The quality of software architecture is one of the crucial success factors for the development of large and/or complex systems. Therefore, a good software architect plays a key role in every demanding project: She or he has the overview of the overall system and sets the framework for the implementation. In order to be successful in this task, software architects need well-founded and encompassing knowledge about design, which exceeds pure programming and specific spe- cialization a...

  1. Enterprise Architecture Evaluation Components

    OpenAIRE

    Niemi, Eetu; Ylimäki, Tanja

    2008-01-01

    Enterprise Architecture (EA) is a holistic view of an organization, including the viewpoints of business, information, systems and technology. It is stated to provide significant benefits to organizations, and is therefore of interest for both academics and practitioners. However, evaluating EA, or its benefits, is difficult. Moreover, the studies on EA evaluation are mostly inconsistent, and almost omit the planning aspect of evaluation. This study suggests the evaluation components that nee...

  2. Sustainable Enterprise Architecture

    CERN Document Server

    Hausman, Kirk

    2011-01-01

    Providing guidance that can be applied to an enterprise of any scale, this book supplies IT practitioners with the tools needed to present enterprise architecture concepts to non-technical stakeholders. Rather than focusing on a single governance framework, the text explains how to develop successful and sustainable enterprise deployments in any setting. Coverage includes general security practices, common threats, storage mechanisms, and the impact of virtualization. The author presents functional considerations for developing and maintaining extended enterprise networks using practices teste

  3. Future database machine architectures

    OpenAIRE

    Hsiao, David K.

    1984-01-01

    There are many software database management systems available on many general-purpose computers ranging from micros to super-mainframes. Database machines as backened computers can offload the database management work from the mainframe so that we can retain the same mainframe longer. However, the database backend must also demonstrate lower cost, higher performance, and newer functionality. Some of the fundamental architecture issues in the design of high-performance and great-capacity datab...

  4. Influence of ATM-Mediated DNA Damage Response on Genomic Variation in Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Lu, Junjie; Li, Hu; Baccei, Anna; Sasaki, Takayo; Gilbert, David M; Lerou, Paul H

    2016-05-01

    Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM-deficient iPSCs relative to wild-type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral (RV) reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DDR reveals unique vulnerability of early replicating open chromatin to RV vectors. PMID:26935587

  5. Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Madsen, O.D.; Andersen, L.C.; Michelsen, B.; Owerbach, D.; Larsson, L.I.; Lernmark, A.; Steiner, D.F. (Hagedorn Research Laboratory, Gentofte (Denmark))

    1988-09-01

    The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. The authors propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression.

  6. Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo

    International Nuclear Information System (INIS)

    The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. The authors propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression

  7. Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines.

    Science.gov (United States)

    Ghosheh, Nidal; Olsson, Björn; Edsbagge, Josefina; Küppers-Munther, Barbara; Van Giezen, Mariska; Asplund, Annika; Andersson, Tommy B; Björquist, Petter; Carén, Helena; Simonsson, Stina; Sartipy, Peter; Synnergren, Jane

    2016-01-01

    Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models. PMID:26949401

  8. The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming

    Institute of Scientific and Technical Information of China (English)

    Athanasia D Panopoulos; Margaret Lutz; W Travis Berggren; Kun Zhang; Ronald M Evans; Gary Siuzdak; Juan Carlos Izpisua Belmonte; Oscar Yanes; SergioRuiz; Yasuyuki S Kida; Dinh Diep; Ralf Tautenhahn; Aida Herrerias; Erika M Batchelder; Nongluk Plongthongkum

    2012-01-01

    Metabolism is vital to every aspect of cell function,yet the metabolome of induced pluripotent stem cells (iPSCs)remains largely unexplored.Here we report,using an untargeted metabolomics approach,that human iPSCs share a pluripotent metabolomic signature with embryonic stem cells (ESCs) that is distinct from their parental cells,and that is characterized by changes in metabolites involved in cellular respiration.Examination of cellular bioenergetics corroborated with our metabolomic analysis,and demonstrated that somatic cells convert from an oxidative state to a glycolytic state in pluripotency.Interestingly,the bioenergetics of various somatic cells correlated with their reprogramming efficiencies.We further identified metabolites that differ between iPSCs and ESCs,which revealed novel metabolic pathways that play a critical role in regulating somatic cell reprogramming.Our findings are the first to globally analyze the metabolome of iPSCs,and provide mechanistic insight into a new layer of regulation involved in inducing pluripotency,and in evaluating iPSC and ESC equivalence.

  9. Transient Acquisition of Pluripotency During Somatic Cell Transdifferentiation with iPSC Reprogramming Factors

    Science.gov (United States)

    Maza, Itay; Caspi, Inbal; Zviran, Asaf; Chomsky, Elad; Rais, Yoach; Viukov, Sergey; Geula, Shay; Buenrostro, Jason D.; Weinberger, Leehee; Krupalnik, Vladislav; Hanna, Suhair; Zerbib, Mirie; Dutton, James R.; Greenleaf, William J.; Massarwa, Rada; Novershtern, Noa; Hanna, Jacob H.

    2015-01-01

    Somatic cells can be transdifferentiated to other cell types without passing through a pluripotent state by ectopic expression of appropriate transcription factors1,2. Recent reports have proposed an alternative transdifferentiation method in which fibroblasts are directly converted to various mature somatic cell types by brief expression of the induced pluripotent stem cell (iPSC) reprogramming factors Oct4, Sox2, Klf4 and c-Myc (OSKM) followed by cell expansion in media that promote lineage differentiation3–6. Here we test this method using genetic lineage tracing for expression of endogenous Nanog and Oct4 and for X chromosome reactivation, as these events mark acquisition of pluripotency. We show that the vast majority of reprogrammed cardiomyocytes or neural stem cells obtained from mouse fibroblasts by OSKM-induced transdifferentiation pass through a transient pluripotent state, and that their derivation is molecularly coupled to iPSC formation mechanisms. Our findings underscore the importance of defining trajectories during cell reprogramming by different methods. PMID:26098448

  10. Origin of pluripotent germ cell tumours: the role of microenvironment during embryonic development

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Sonne, Si Brask; Ottesen, Anne Marie;

    2008-01-01

    virtually any type of tissue and form teratomas (non-seminomas). CIS cells display a close phenotypic similarity to fetal germ cells (primordial germ cells or gonocytes) suggesting an origin due to a developmental delay or arrest of differentiation of early germ cells. The pluripotency of these neoplasms...

  11. Generation of Pig Induced Pluripotent Stem Cells with a Drug-Inducible System

    Institute of Scientific and Technical Information of China (English)

    Zhao Wu; Jijun Chen; Jiangtao Ren; Lei Bao; Jing Liao; Chun Cui; Linjun Rao; Hui Li; Yijun Gu; Huiming Dai; Hui Zhu; Xiaokun Teng; Lu Cheng; Lei Xiao

    2009-01-01

    Domesticated ungulate pluripotent embryonic stem (ES) cell lines would be useful for generating precise gene-modified animals. To date, many efforts have been made to establish domesticated ungulate pluripotent ES cells from early embryos without success.Here, we report the generation of porcine-induced pluripotent stem (iPS) cells using drug-inducible expression of defined factors.We showed that porcine iPS cells expressed alkaline phosphatase, SSEA3, SSEA4, Tra-1-60, Tra-1-81, Oct3/4, Nanog, Sox2, Rex1 and CDH1. Pig iPS cells expressed high levels of telomerase activity and showed normal karyotypes. These cells could differentiate into cell types of all three germ layers in vitro and in teratomas. Our study reveals properties of porcine pluripotent stem cells that may facilitate the eventual establishment of porcine ES cells. Moreover, the porcine iPS cells produced may be directly useful for the generation of precise gene-modified pigs.

  12. DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells

    Directory of Open Access Journals (Sweden)

    Hsu-Hsin Chen

    2014-11-01

    Full Text Available The scarcity of primordial germ cells (PGCs in the developing mammalian embryo hampers robust biochemical analysis of the processes that underlie early germ cell formation. Here, we demonstrate that DAZL, a germ cell-specific RNA binding protein, is a robust PGC marker during in vitro germ cell development. Using Dazl-GFP reporter ESCs, we demonstrate that DAZL plays a central role in a large mRNA/protein interactive network that blocks the translation of core pluripotency factors, including Sox2 and Sall4, as well as of Suz12, a polycomb family member required for differentiation of pluripotent cells. Thus, DAZL limits both pluripotency and somatic differentiation in nascent PGCs. In addition, we observed that DAZL associates with mRNAs of key Caspases and similarly inhibits their translation. This elegant fail-safe mechanism ensures that, whereas loss of DAZL results in prolonged expression of pluripotency factors, teratoma formation is avoided due to the concomitant activation of the apoptotic cascade.

  13. Defining the genomic signature of totipotency and pluripotency during early human development.

    Directory of Open Access Journals (Sweden)

    Amparo Galan

    Full Text Available The genetic mechanisms governing human pre-implantation embryo development and the in vitro counterparts, human embryonic stem cells (hESCs, still remain incomplete. Previous global genome studies demonstrated that totipotent blastomeres from day-3 human embryos and pluripotent inner cell masses (ICMs from blastocysts, display unique and differing transcriptomes. Nevertheless, comparative gene expression analysis has revealed that no significant differences exist between hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental progression. To understand early human stages evolution, we developed an undifferentiation network signature (UNS and applied it to a differential gene expression profile between single blastomeres from day-3 embryos, ICMs and hESCs. This allowed us to establish a unique signature composed of highly interconnected genes characteristic of totipotency (61 genes, in vivo pluripotency (20 genes, and in vitro pluripotency (107 genes, and which are also proprietary according to functional analysis. This systems biology approach has led to an improved understanding of the molecular and signaling processes governing human pre-implantation embryo development, as well as enabling us to comprehend how hESCs might adapt to in vitro culture conditions.

  14. Identification of polymer surface adsorbed proteins implicated in pluripotent human embryonic stem cell expansion.

    Science.gov (United States)

    Hammad, Moamen; Rao, Wei; Smith, James G W; Anderson, Daniel G; Langer, Robert; Young, Lorraine E; Barrett, David A; Davies, Martyn C; Denning, Chris; Alexander, Morgan R

    2016-08-16

    Improved biomaterials are required for application in regenerative medicine, biosensing, and as medical devices. The response of cells to the chemistry of polymers cultured in media is generally regarded as being dominated by proteins adsorbed to the surface. Here we use mass spectrometry to identify proteins adsorbed from a complex mouse embryonic fibroblast (MEF) conditioned medium found to support pluripotent human embryonic stem cell (hESC) expansion on a plasma etched tissue culture polystyrene surface. A total of 71 proteins were identified, of which 14 uniquely correlated with the surface on which pluripotent stem cell expansion was achieved. We have developed a microarray combinatorial protein spotting approach to test the potential of these 14 proteins to support expansion of a hESC cell line (HUES-7) and a human induced pluripotent stem cell line (ReBl-PAT) on a novel polymer (N-(4-Hydroxyphenyl) methacrylamide). These proteins were spotted to form a primary array yielding several protein mixture 'hits' that enhanced cell attachment to the polymer. A second array was generated to test the function of a refined set of protein mixtures. We found that a combination of heat shock protein 90 and heat shock protein-1 encourage elevated adherence of pluripotent stem cells at a level comparable to fibronectin pre-treatment. PMID:27466628

  15. Robust generation and expansion of skeletal muscle progenitors and myocytes from human pluripotent stem cells.

    Science.gov (United States)

    Shelton, Michael; Kocharyan, Avetik; Liu, Jun; Skerjanc, Ilona S; Stanford, William L

    2016-05-15

    Human pluripotent stem cells provide a developmental model to study early embryonic and tissue development, tease apart human disease processes, perform drug screens to identify potential molecular effectors of in situ regeneration, and provide a source for cell and tissue based transplantation. Highly efficient differentiation protocols have been established for many cell types and tissues; however, until very recently robust differentiation into skeletal muscle cells had not been possible unless driven by transgenic expression of master regulators of myogenesis. Nevertheless, several breakthrough protocols have been published in the past two years that efficiently generate cells of the skeletal muscle lineage from pluripotent stem cells. Here, we present an updated version of our recently described 50-day protocol in detail, whereby chemically defined media are used to drive and support muscle lineage development from initial CHIR99021-induced mesoderm through to PAX7-expressing skeletal muscle progenitors and mature skeletal myocytes. Furthermore, we report an optional method to passage and expand differentiating skeletal muscle progenitors approximately 3-fold every 2weeks using Collagenase IV and continued FGF2 supplementation. Both protocols have been optimized using a variety of human pluripotent stem cell lines including patient-derived induced pluripotent stem cells. Taken together, our differentiation and expansion protocols provide sufficient quantities of skeletal muscle progenitors and myocytes that could be used for a variety of studies. PMID:26404920

  16. SILAC Proteomics of Planarians Identifies Ncoa5 as a Conserved Component of Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Alexander Böser

    2013-11-01

    Full Text Available Planarian regeneration depends on the presence of pluripotent stem cells in the adult. We developed an in vivo stable isotope labeling by amino acids in cell culture (SILAC protocol in planarians to identify proteins that are enriched in planarian stem cells. Through a comparison of SILAC proteomes of normal and stem cell-depleted planarians and of a stem cell-enriched population of sorted cells, we identified hundreds of stem cell proteins. One of these is an ortholog of nuclear receptor coactivator-5 (Ncoa5/CIA, which is known to regulate estrogen-receptor-mediated transcription in human cells. We show that Ncoa5 is essential for the maintenance of the pluripotent stem cell population in planarians and that a putative mouse ortholog is expressed in pluripotent cells of the embryo. Our study thus identifies a conserved component of pluripotent stem cells, demonstrating that planarians, in particular, when combined with in vivo SILAC, are a powerful model in stem cell research.

  17. Derivation of Pluripotent Cells from Mouse SSCs Seems to Be Age Dependent

    Directory of Open Access Journals (Sweden)

    Hossein Azizi

    2016-01-01

    Full Text Available Here, we aimed to answer important and fundamental questions in germ cell biology with special focus on the age of the male donor cells and the possibility to generate embryonic stem cell- (ESC- like cells. While it is believed that spermatogonial stem cells (SSCs and truly pluripotent ESC-like cells can be isolated from adult mice, it remained unknown if the spontaneous conversion of SSCs to ESC-like cells fails at some age. Similarly, there have been differences in the literature about the duration of cultures during which ESC-like cells may appear. We demonstrate the possibility to derive ESC-like cells from SSC cultures until they reach adolescence or up to 7 weeks of age, but we point out the impossibility to derive these cells from older, mature adult mice. The inability of real adult SSCs to shift to a pluripotent state coincides with a decline in expression of the core pluripotency genes Oct4, Nanog, and Sox2 in SSCs with age. At the same time genes of the spermatogonial differentiation pathway increase. The generated ESC-like cells were similar to ESCs and express pluripotency markers. In vitro they differentiate into all three germ lineages; they form complex teratomas after transplantation in SCID mice and produce chimeric mice.

  18. Expand and Regularize Federal Funding for Human Pluripotent Stem Cell Research

    Science.gov (United States)

    Owen-Smith, Jason; Scott, Christopher Thomas; McCormick, Jennifer B.

    2012-01-01

    Human embryonic stem cell (hESC) research has sparked incredible scientific and public excitement, as well as significant controversy. hESCs are pluripotent, which means, in theory, that they can be differentiated into any type of cell found in the human body. Thus, they evoke great enthusiasm about potential clinical applications. They are…

  19. Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature

    Institute of Scientific and Technical Information of China (English)

    Huansheng Xu; Ibrahim J Domian; Erding Hu; Robert Willette; John Lepore; Alexander Meissner; Zhong Wang; Kenneth R Chien; B Alexander Yi; Hao Wu; Christoph Bock; Hongcang Gu; Kathy O Lui; Joo-Hye C Park; Ying Shao; Alyssa K Riley

    2012-01-01

    Cardiomyocytes derived from pluripotent stem cells can be applied in drug testing,disease modeling and cellbased therapy.However,without procardiogenic growth factors,the efficiency of cardiomyogenesis from pluripotent stem cells is usually low and the resulting cardiomyocyte population is heterogeneous.Here,we demonstrate that induced pluripotent stem cells (iPSCs) can be derived from murine ventricular myocytes (VMs),and consistent with other reports of iPSCs derived from various somatic cell types,VM-derived iPSCs (ViPSCs) exhibit a markedly higher propensity to spontaneously differentiate into beating cardiomyocytes as compared to genetically matched embryonic stem cells (ESCs) or iPSCs derived from tail-tip fibroblasts.Strikingly,the majority of ViPSC-derived cardiomyocytes display a ventricular phenotype.The enhanced ventricular myogenesis in ViPSCs is mediated via increased numbers of cardiovascular progenitors at early stages of differentiation.In order to investigate the mechanism of enhanced ventricular myogenesis from ViPSCs,we performed global gene expression and DNA methylation analysis,which revealed a distinct epigenetic signature that may be involved in specifying the VM fate in pluripotent stem cells.

  20. The Path from Pluripotency to Skeletal Muscle: Developmental Myogenesis Guides the Way

    Science.gov (United States)

    Hicks, Michael; Pyle, April

    2016-01-01

    Following cues from mouse embryogenesis, Chal et al. (2015) identified key regulators of skeletal myogenesis from mouse and human pluripotent stem cells. Emerging myogenic progenitors were specified to form multinucleated fibers that enabled development of quiescent, satellite cell-like progenitors and a model for Duchenne Muscular Dystrophy. PMID:26340524