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Sample records for cells generate multiple

  1. Multiple Exciton Generation for Highly Efficient Solar Cells

    Science.gov (United States)

    Nozik, Arthur

    2007-03-01

    In order to utilize solar power for the production of electricity and fuel on a massive scale, it will be necessary to develop solar photon conversion systems that have an appropriate combination of high efficiency and low capital cost (/m^2). One new potential approach to high solar cell efficiency is to utilize the unique properties of semiconductor quantum dot nanostructures to control the relaxation dynamics of photogenerated carriers to produce either enhanced photocurrent through efficient multiple exciton generation (MEG) or enhanced photopotential through hot electron transport and transfer processes. To achieve these desirable effects it is necessary to understand and control the dynamics of electron relaxation, cooling, multiple exciton generation , transport, and interfacial electron transfer of the photogenerated carriers with fs to ns time resolution. We have been studying these fundamental dynamics in bulk and nanoscale semiconductors (quantum dots, quantum wires, and quantum wells) using femtosecond transient absorption, photoluminescence, and THz spectroscopy. This work will be summarized and recent advances in creating multiple excitons from a single photon will be discussed, including a unique model to explain efficient MEG based on the coherent superposition of multiple excitonic states. Various possible configurations for quantum dot solar cells that could produce ultra-high conversion efficiencies for the production of electricity, as well as for producing solar fuels (for example, hydrogen from water splitting), will be discussed, along with associated thermodynamic calculations that show the increase in the maximum theoretical gain in solar photon conversion efficiency for both electricity and fuel production.

  2. Multiple-exciton generation in lead selenide nanorod solar cells with external quantum efficiencies exceeding 120.

    Science.gov (United States)

    Davis, Nathaniel J L K; Böhm, Marcus L; Tabachnyk, Maxim; Wisnivesky-Rocca-Rivarola, Florencia; Jellicoe, Tom C; Ducati, Caterina; Ehrler, Bruno; Greenham, Neil C

    2015-01-01

    Multiple-exciton generation-a process in which multiple charge-carrier pairs are generated from a single optical excitation-is a promising way to improve the photocurrent in photovoltaic devices and offers the potential to break the Shockley-Queisser limit. One-dimensional nanostructures, for example nanorods, have been shown spectroscopically to display increased multiple exciton generation efficiencies compared with their zero-dimensional analogues. Here we present solar cells fabricated from PbSe nanorods of three different bandgaps. All three devices showed external quantum efficiencies exceeding 100% and we report a maximum external quantum efficiency of 122% for cells consisting of the smallest bandgap nanorods. We estimate internal quantum efficiencies to exceed 150% at relatively low energies compared with other multiple exciton generation systems, and this demonstrates the potential for substantial improvements in device performance due to multiple exciton generation.

  3. Multiple-exciton generation in lead selenide nanorod solar cells with external quantum efficiencies exceeding 120%

    Science.gov (United States)

    Davis, Nathaniel J. L. K.; Böhm, Marcus L.; Tabachnyk, Maxim; Wisnivesky-Rocca-Rivarola, Florencia; Jellicoe, Tom C.; Ducati, Caterina; Ehrler, Bruno; Greenham, Neil C.

    2015-01-01

    Multiple-exciton generation—a process in which multiple charge-carrier pairs are generated from a single optical excitation—is a promising way to improve the photocurrent in photovoltaic devices and offers the potential to break the Shockley–Queisser limit. One-dimensional nanostructures, for example nanorods, have been shown spectroscopically to display increased multiple exciton generation efficiencies compared with their zero-dimensional analogues. Here we present solar cells fabricated from PbSe nanorods of three different bandgaps. All three devices showed external quantum efficiencies exceeding 100% and we report a maximum external quantum efficiency of 122% for cells consisting of the smallest bandgap nanorods. We estimate internal quantum efficiencies to exceed 150% at relatively low energies compared with other multiple exciton generation systems, and this demonstrates the potential for substantial improvements in device performance due to multiple exciton generation. PMID:26411283

  4. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    International Nuclear Information System (INIS)

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development

  5. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    Energy Technology Data Exchange (ETDEWEB)

    Webb, Carol F., E-mail: carol-webb@omrf.org [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Ratliff, Michelle L., E-mail: michelle-ratliff@omrf.org [Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Powell, Rebecca, E-mail: rebeccapowell@gmail.com [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Wirsig-Wiechmann, Celeste R., E-mail: celeste-wirsig@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Lakiza, Olga, E-mail: olga-lakiza@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Obara, Tomoko, E-mail: tomoko-obara@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2015-08-07

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

  6. Efficient Generation of Myelinating Oligodendrocytes from Primary Progressive Multiple Sclerosis Patients by Induced Pluripotent Stem Cells

    OpenAIRE

    Panagiotis Douvaras; Jing Wang; Matthew Zimmer; Stephanie Hanchuk; Melanie A. O’Bara; Saud Sadiq; Fraser J. Sim; James Goldman; Valentina Fossati

    2014-01-01

    Summary Multiple sclerosis (MS) is a chronic demyelinating disease of unknown etiology that affects the CNS. While current therapies are primarily directed against the immune system, the new challenge is to address progressive MS with remyelinating and neuroprotective strategies. Here, we develop a highly reproducible protocol to efficiently derive oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes from induced pluripotent stem cells (iPSCs). Key elements of our protocol incl...

  7. Efficient Generation of NKX6-1+ Pancreatic Progenitors from Multiple Human Pluripotent Stem Cell Lines

    Directory of Open Access Journals (Sweden)

    M. Cristina Nostro

    2015-04-01

    Full Text Available Human pluripotent stem cells (hPSCs represent a renewable source of pancreatic beta cells for both basic research and therapeutic applications. Given this outstanding potential, significant efforts have been made to identify the signaling pathways that regulate pancreatic development in hPSC differentiation cultures. In this study, we demonstrate that the combination of epidermal growth factor (EGF and nicotinamide signaling induces the generation of NKX6-1+ progenitors from all hPSC lines tested. Furthermore, we show that the size of the NKX6-1+ population is regulated by the duration of treatment with retinoic acid, fibroblast growth factor 10 (FGF10, and inhibitors of bone morphogenetic protein (BMP and hedgehog signaling pathways. When transplanted into NOD scid gamma (NSG recipients, these progenitors differentiate to give rise to exocrine and endocrine cells, including monohormonal insulin+ cells. Together, these findings provide an efficient and reproducible strategy for generating highly enriched populations of hPSC-derived beta cell progenitors for studies aimed at further characterizing their developmental potential in vivo and deciphering the pathways that regulate their maturation in vitro.

  8. Multiple granular cell tumor.

    Science.gov (United States)

    Jones, J K; Kuo, T T; Griffiths, C M; Itharat, S

    1980-10-01

    Eleven cases of granular cell tumor were reviewed. In two of the cases multiple sites of involvement were seen. The tumor occurred in the oral cavity in both of these cases and each was initially wrongly diagnosed as squamous cell carcinoma. The most common site was the subcutaneous tissue (nine patients) and the tongue was involved in three cases. In one patient the parotid gland was involved. Eight of the patients were females and three were males; seven were black and four were white. The importance of differentiating between squamous cell carcinoma and granular cell tumor is stressed, as is the need for a simple wide surgical excision. PMID:7421377

  9. 46 CFR 183.322 - Multiple generators.

    Science.gov (United States)

    2010-10-01

    ... switchboard, except for the circuit breakers of a generator operated in parallel with another generator when...) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.322 Multiple generators. When a vessel... must be met: (a) Each generator must have an independent prime mover; and (b) The generator...

  10. Fuel cell generator

    International Nuclear Information System (INIS)

    A high temperature solid electrolyte fuel cell generator comprising a housing means defining a plurality of chambers including a generator chamber and a combustion products chamber, a porous barrier separating the generator and combustion product chambers, a plurality of elongated annular fuel cells each having a closed end and an open end with the open ends disposed within the combustion product chamber, the cells extending from the open end through the porous barrier and into the generator chamber, a conduit for each cell, each conduit extending into a portion of each cell disposed within the generator chamber, each conduit having means for discharging a first gaseous reactant within each fuel cell, exhaust means for exhausting the combustion product chamber, manifolding means for supplying the first gaseous reactant to the conduits with the manifolding means disposed within the combustion product chamber between the porous barrier and the exhaust means and the manifolding means further comprising support and bypass means for providing support of the manifolding means within the housing while allowing combustion products from the first and a second gaseous reactant to flow past the manifolding means to the exhaust means, and means for flowing the second gaseous reactant into the generator chamber

  11. Harmonic generation with multiple wiggler schemes

    Energy Technology Data Exchange (ETDEWEB)

    Bonifacio, R.; De Salvo, L.; Pierini, P. [Universita degli Studi, Milano (Italy)

    1995-02-01

    In this paper the authors give a simple theoretical description of the basic physics of the single pass high gain free electron laser (FEL), describing in some detail the FEL bunching properties and the harmonic generation technique with a multiple-wiggler scheme or a high gain optical klystron configuration.

  12. Cell Therapy for Multiple Sclerosis

    OpenAIRE

    Ben-Hur, Tamir

    2011-01-01

    The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic pl...

  13. The Hemopoietic Stem Cell Niche Versus the Microenvironment of the Multiple Myeloma-Tumor Initiating Cell

    OpenAIRE

    Zipori, Dov

    2010-01-01

    Multiple myeloma cells are reminiscent of hemopoietic stem cells in their strict dependence upon the bone marrow microenvironment. However, from all other points of view, multiple myeloma cells differ markedly from stem cells. The cells possess a mature phenotype and secrete antibodies, and have thus made the whole journey to maturity, while maintaining a tumor phenotype. Not much credence was given to the possibility that the bulk of plasma-like multiple myeloma tumor cells is generated from...

  14. 46 CFR 120.322 - Multiple generators.

    Science.gov (United States)

    2010-10-01

    ... PASSENGERS OR WITH OVERNIGHT ACCOMMODATIONS FOR MORE THAN 49 PASSENGERS ELECTRICAL INSTALLATION Power Sources... of a generator operated in parallel with another generator when the installation meets §§...

  15. The generation of sex cells

    OpenAIRE

    Deglincerti, Alessia; Brivanlou, Ali H.

    2015-01-01

    Primordial germ cells (PGCs) are the earliest population of germ cells established during embryonic development and constitute the beginning of the totipotent state. A recent study provides a new protocol for the efficient generation of PGC-like cells from human embryonic stem cells, providing an in vitro platform to study human PGC differentiation and specification.

  16. Multiple Scenario Generation of Subsurface Models

    DEFF Research Database (Denmark)

    Cordua, Knud Skou

    developments of these strategies have to be provided. Moreover, applications of these strategies will reveal the practical implications of these consistent formulations. This will in particular be of great importance when it comes to assessments related cases of high risk such as human health or resources......, e.g., training images that expresses structural, lithological, or textural features. Statistics obtained from these types of observations will be referred to as sample models. Geostatistical sampling algorithms use a sample model as input and produce multiple realizations of the model parameters....... An example of sampling the posterior probability distribution of a computationally hard full waveform inverse problem using prior information based on multiple-point statistics, obtained from a training image, is demonstrated. For some computationally challenging inverse problems, a sample from the posterior...

  17. Ontology-based multiple choice question generation.

    Science.gov (United States)

    Al-Yahya, Maha

    2014-01-01

    With recent advancements in Semantic Web technologies, a new trend in MCQ item generation has emerged through the use of ontologies. Ontologies are knowledge representation structures that formally describe entities in a domain and their relationships, thus enabling automated inference and reasoning. Ontology-based MCQ item generation is still in its infancy, but substantial research efforts are being made in the field. However, the applicability of these models for use in an educational setting has not been thoroughly evaluated. In this paper, we present an experimental evaluation of an ontology-based MCQ item generation system known as OntoQue. The evaluation was conducted using two different domain ontologies. The findings of this study show that ontology-based MCQ generation systems produce satisfactory MCQ items to a certain extent. However, the evaluation also revealed a number of shortcomings with current ontology-based MCQ item generation systems with regard to the educational significance of an automatically constructed MCQ item, the knowledge level it addresses, and its language structure. Furthermore, for the task to be successful in producing high-quality MCQ items for learning assessments, this study suggests a novel, holistic view that incorporates learning content, learning objectives, lexical knowledge, and scenarios into a single cohesive framework.

  18. Multiple myeloma cancer stem cells

    Science.gov (United States)

    Gao, Minjie; Kong, Yuanyuan; Yang, Guang; Gao, Lu; Shi, Jumei

    2016-01-01

    Multiple myeloma (MM) remains incurable despite much progress that has been made in the treatment of the disease. MM cancer stem cell (MMSC), a rare subpopulation of MM cells with the capacity for self-renewal and drug resistance, is considered to lead to disease relapse. Several markers such as side population (SP) and ALDH1+ have been used to identify MMSCs. However, ideally and more precisely, the identification of the MMSCs should rely on MMSCs phenotype. Unfortunately the MMSC phenotype has not been properly defined yet. Drug resistance is the most important property of MMSCs and contributes to disease relapse, but the mechanisms of drug resistance have not been fully understood. The major signaling pathways involved in the regulation of self-renewal and differentiation of MMSCs include Hedgehog (Hh), Wingless (Wnt), Notch and PI3K/Akt/mTOR. However, the precise role of these signaling pathways needs to be clarified. It has been reported that the microRNA profile of MMSCs is remarkably different than that of non-MMSCs. Therefore, the search for targeting MMSCs has also been focused on microRNAs. Complex and mutual interactions between the MMSC and the surrounding bone marrow (BM) microenvironment sustain self-renewal and survival of MMSC. However, the required molecules for the interaction of the MMSC and the surrounding BM microenvironment need to be further identified. In this review, we summarize the current state of knowledge of MMSCs regarding their phenotype, mechanisms of drug resistance, signaling pathways that regulate MMSCs self-renewal and differentiation, abnormal microRNAs expression, and their interactions with the BM microenvironment. PMID:27007154

  19. Tag cloud generation for results of multiple keywords queries

    DEFF Research Database (Denmark)

    Leginus, Martin; Dolog, Peter; Lage, Ricardo Gomes

    2013-01-01

    In this paper we study tag cloud generation for retrieved results of multiple keyword queries. It is motivated by many real world scenarios such as personalization tasks, surveillance systems and information retrieval tasks defined with multiple keywords. We adjust the state-of-the-art tag cloud...... generation techniques for multiple keywords query results. Consequently, we conduct the extensive evaluation on top of three distinct collaborative tagging systems. The graph-based methods perform significantly better for the Movielens and Bibsonomy datasets. Tag cloud generation based on maximal coverage...

  20. Generating Cognitive Dissonance in Student Interviews through Multiple Representations

    Science.gov (United States)

    Linenberger, Kimberly J.; Bretz, Stacey Lowery

    2012-01-01

    This study explores what students understand about enzyme-substrate interactions, using multiple representations of the phenomenon. In this paper we describe our use of the 3 Phase-Single Interview Technique with multiple representations to generate cognitive dissonance within students in order to uncover misconceptions of enzyme-substrate…

  1. Fast generation of dendritic cells

    DEFF Research Database (Denmark)

    Kvistborg, P; Bøgh, Marie; Claesson, M H;

    2009-01-01

    Dendritic cells (DC) are potent antigen presenting cells capable of inducing immune responses. DC are widely used as vaccine adjuvant in experimental clinical settings. DC-based vaccines are normally generated using a standard 8day DC protocol (SDDC). In attempts to shorten the vaccine production...... SDDC to the IL-10 inducing stimulus of TLR ligands (R848 and LPS). Thus to determine the clinical relevance of fast DC protocols in cancer settings, small phase I trials should be conducted monitoring regulatory T cells carefully....

  2. Generation of multiple excitons in Ag2S quantum dots: Single high-energy versus multiple-photon excitation

    KAUST Repository

    Sun, Jingya

    2014-02-20

    We explored biexciton generation via carrier multiplication (or multiple-exciton generation) by high-energy photons and by multiple-photon absorption in Ag2S quantum dots (QDs) using femtosecond broad-band transient absorption spectroscopy. Irrespective of the size of the QDs and how the multiple excitons are generated in the Ag2S QDs, two distinct characteristic time constants of 9.6-10.2 and 135-175 ps are obtained for the nonradiative Auger recombination of the multiple excitons, indicating the existence of two binding excitons, namely, tightly bound and weakly bound excitons. More importantly, the lifetimes of multiple excitons in Ag 2S QDs were about 1 and 2 orders of magnitude longer than those of comparable size PbS QDs and single-walled carbon nanotubes, respectively. This result is significant because it suggests that by utilizing an appropriate electron acceptor, there is a higher possibility to extract multiple electron-hole pairs in Ag2S QDs, which should improve the performance of QD-based solar cell devices. © 2014 American Chemical Society.

  3. Human memory T cells: generation, compartmentalization and homeostasis

    OpenAIRE

    Farber, Donna L.; Yudanin, Naomi A.; Restifo, Nicholas P

    2013-01-01

    Memory T cells comprise the most abundant lymphocyte population in the body for the majority of one’s lifetime; however, our understanding of memory T cell generation, function and maintenance mainly derives from mouse studies, which cannot recapitulate the decades-long exposure to multiple pathogens that occurs in humans. Here, we review studies focused on human memory T cells that reveal key properties including subset heterogeneity and diverse tissue residence in multiple mucosal and lymph...

  4. Color Correction in Multiple Generation Reproduction Using Digital Watermarking

    Institute of Scientific and Technical Information of China (English)

    Zhigang Fan; Shen-ge Wang; Hui Cheng

    2004-01-01

    In most existing color reproduction systems, color correction is performed in an open-looped fashion.For multiple generation color copying, color fidelity cannot be guaranteed as the errors introduced in color correction may accumulate. A method of solving the error accumulation problem by embedding color information as invisible digital watermark in hardcopies is proposed. When the hardcopy is scanned, the embedded information can be retrieved to provide real-time calibration. As the method is close-looped in nature, it may reduce error accumulation and improve color fidelity, particularly when copies go through multiple generation reproduction.

  5. Third generation photovoltaics based on multiple exciton generation in quantum confined semiconductors.

    Science.gov (United States)

    Beard, Matthew C; Luther, Joseph M; Semonin, Octavi E; Nozik, Arthur J

    2013-06-18

    Improving the primary photoconversion process in a photovoltaiccell by utilizing the excess energy that is otherwise lost as heat can lead to an increase in the overall power conversion efficiency (PCE). Semiconductor nanocrystals (NCs) with at least one dimension small enough to produce quantum confinement effects provide new ways of controlling energy flow not achievable in thin film or bulk semiconductors. Researchers have developed various strategies to incorporate these novel structures into suitable solar conversion systems. Some of these methods could increase the PCE past the Shockley-Queisser (SQ) limit of ∼33%, making them viable "third generation photovoltaic" (TGPV) cell architectures. Surpassing the SQ limit for single junction solar cells presents both a scientific and a technological challenge, and the use of semiconductor NCs to enhance the primary photoconversion process offers a promising potential solution. The NCs are synthesized via solution phase chemical reactions producing stable colloidal solutions, where the reaction conditions can be modified to produce a variety of shapes, compositions, and structures. The confinement of the semiconductor NC in one dimension produces quantum films, wells, or discs. Two-dimensional confinement leads to quantum wires or rods (QRs), and quantum dots (QDs) are three-dimensionally confined NCs. The process of multiple exciton generation (MEG) converts a high-energy photon into multiple electron-hole pairs. Although many studies have demonstrated that MEG is enhanced in QDs compared with bulk semiconductors, these studies have either used ultrafast spectroscopy to measure the photon-to-exciton quantum yields (QYs) or theoretical calculations. Implementing MEG in a working solar cell has been an ongoing challenge. In this Account, we discuss the status of MEG research and strategies towards implementing MEG in working solar cells. Recently we showed an external quantum efficiency for photocurrent of greater

  6. Dysfunctional T regulatory cells in multiple myeloma

    OpenAIRE

    Prabhala, Rao H.; Neri, Paola; Bae, Jooeun E.; Tassone, Pierfrancesco; Shammas, Masood A.; Allam, Charles K.; Daley, John F.; Chauhan, Dharminder; Blanchard, Elizabeth; Thatte, Hemant S.; Anderson, Kenneth C; Munshi, Nikhil C.

    2006-01-01

    Multiple myeloma (MM) is characterized by the production of monoclonal immunoglobulin and is associated with suppressed uninvolved immunoglobulins and dysfunctional T-cell responses. The biologic basis of this dysfunction remains ill defined. Because T regulatory (Treg) cells play an important role in suppressing normal immune responses, we evaluated the potential role of Treg cells in immune dysfunction in MM. We observed a significant increase in CD4+CD25+ T cells in patients with monoclona...

  7. Synchronous Squamous Cell Carcinoma in Multiple Digits

    OpenAIRE

    Abner, Sabra; Redstone, Jeremiah; Chowdhry, Saeed; Kasdan, Morton L.; Wilhelmi, Bradon J.

    2011-01-01

    Cancers of the perionychium are relatively rare occurrences and are often related to chronic inflammation associated with trauma, infection, exposure to ultraviolet radiation, or other carcinogens. Squamous cell carcinoma is the most common tumor reported of the nail bed. Synchronous squamous cell carcinomas of the perionychium have been rarely reported. We present a case of a 46-year-old woman with synchronous squamous cell carcinomas involving both hands and multiple digits. Treatment modal...

  8. Langerhans cell histiocytosis with multiple spinal involvement

    OpenAIRE

    Jiang, Liang; Liu, Xiao Guang; Zhong, Wo Quan; Ma, Qing Jun; Wei, Feng; Yuan, Hui Shu; Dang, Geng Ting; Liu, Zhong Jun

    2010-01-01

    To stress the clinical and radiologic presentation and treatment outcome of Langerhans cell histiocytosis (LCH) with multiple spinal involvements. A total of 42 cases with spinal LCH were reviewed in our hospital and 5 had multifocal spinal lesions. Multiple spinal LCH has been reported in 50 cases in the literature. All cases including ours were analyzed concerning age, sex, clinical and radiologic presentation, therapy and outcome. Of our five cases, three had neurological symptom, four sof...

  9. Enhanced Multiple Exciton Generation in Amorphous Silicon Nanoparticles

    OpenAIRE

    Kryjevski, Andrei; Kilin, Dmitri

    2014-01-01

    Multiple exciton generation (MEG) in nanometer-sized hydrogen-passivated silicon nanowires (NWs), and quasi two-dimensional nanofilms strongly depends on the degree of the core structural disorder as shown by the many-body perturbation theory (MBPT) calculations based on the density functional theory (DFT) simulations. Working to the second order in the electron-photon coupling and in the screened Coulomb interaction we calculate quantum efficiency (QE), the average number of excitons created...

  10. Interactions of multiple spark-generated bubbles with phase differences

    Science.gov (United States)

    Fong, Siew Wan; Adhikari, Deepak; Klaseboer, Evert; Khoo, Boo Cheong

    2009-04-01

    This paper aims to study the complex interaction between multiple bubbles, and to provide a summary and physical explanation of the phenomena observed during the interaction of two bubbles. High-speed photography is utilized to observe the experiments involving multiple spark-generated bubbles. Numerical simulations corresponding to the experiments are performed using the Boundary Element Method (BEM). The bubbles are typically between 3 and 5 mm in radius and are generated either in-phase (at the same time) or with phase differences. Complex phenomena are observed such as bubble splitting, and high-speed jetting inside a bubble caused by another collapsing bubble nearby (termed the ‘catapult’ effect). The two-bubble interactions are broadly classified in a graph according to two parameters: the relative inter-bubble distance and the phase difference (a new parameter introduced). The BEM simulations provide insight into the physics, such as bubble shape changes in detail, and jet velocities. Also presented in this paper are the experimental results of three bubble interactions. The interesting and complex observations of multiple bubble interaction are important for a better understanding of real life applications in medical ultrasonic treatment and ultrasonic cleaning. Many of the three bubble interactions can be explained by isolating bubble pairs and classifying their interaction according to the graph for the two bubble case. This graph can be a useful tool to predict the behavior of multiple bubble interactions.

  11. Human memory T cells: generation, compartmentalization and homeostasis

    Science.gov (United States)

    Farber, Donna L.; Yudanin, Naomi A.; Restifo, Nicholas P.

    2014-01-01

    Memory T cells comprise the most abundant lymphocyte population in the body for the majority of one’s lifetime; however, our understanding of memory T cell generation, function and maintenance mainly derives from mouse studies, which cannot recapitulate the decades-long exposure to multiple pathogens that occurs in humans. Here, we review studies focused on human memory T cells that reveal key properties including subset heterogeneity and diverse tissue residence in multiple mucosal and lymphoid tissue sites. We also discuss how the function and adaptability of human memory T cells depend on spatial and temporal compartmentalization. PMID:24336101

  12. Hematopoietic stem cell transplantation in multiple sclerosis

    DEFF Research Database (Denmark)

    Rogojan, C; Frederiksen, J L

    2009-01-01

    Intensive immunosuppresion followed by hematopoietic stem cell transplantation (HSCT) has been suggested as potential treatment in severe forms of multiple sclerosis (MS). Since 1995 ca. 400 patients have been treated with HSCT. Stabilization or improvement occurred in almost 70% of cases at least...

  13. Smart Energy Management of Multiple Full Cell Powered Applications

    Energy Technology Data Exchange (ETDEWEB)

    MOhammad S. Alam

    2007-04-23

    In this research project the University of South Alabama research team has been investigating smart energy management and control of multiple fuel cell power sources when subjected to varying demands of electrical and thermal loads together with demands of hydrogen production. This research has focused on finding the optimal schedule of the multiple fuel cell power plants in terms of electric, thermal and hydrogen energy. The optimal schedule is expected to yield the lowest operating cost. Our team is also investigating the possibility of generating hydrogen using photoelectrochemical (PEC) solar cells through finding materials for efficient light harvesting photoanodes. The goal is to develop an efficient and cost effective PEC solar cell system for direct electrolysis of water. In addition, models for hydrogen production, purification, and storage will be developed. The results obtained and the data collected will be then used to develop a smart energy management algorithm whose function is to maximize energy conservation within a managed set of appliances, thereby lowering O/M costs of the Fuel Cell power plant (FCPP), and allowing more hydrogen generation opportunities. The Smart Energy Management and Control (SEMaC) software, developed earlier, controls electrical loads in an individual home to achieve load management objectives such that the total power consumption of a typical residential home remains below the available power generated from a fuel cell. In this project, the research team will leverage the SEMaC algorithm developed earlier to create a neighborhood level control system.

  14. Biorthogonal multiple wavelets generated by vector refinement equation

    Institute of Scientific and Technical Information of China (English)

    Song LI; Jun XIAN

    2007-01-01

    Biorthogonal multiple wavelets are generated from refinable function vectors by using the multiresolution analysis. In this paper we provide a general method for the construction of compactly supported biorthogonal multiple wavelets by refinable function vectors which are the solutions of vector refinement equations of the formψ(x) =∑α∈Zs α(α)ψ(Mx-α), x ∈ Rs,sequence of r × r matrices called the refinement mask, and M is an s × s integer matrix such that limn→∞ M-n = 0. Our characterizations are in the general setting and the main results of this paper are the real extensions of some known results.

  15. Biorthogonal multiple wavelets generated by vector refinement equation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Biorthogonal multiple wavelets are generated from refinable function vectors by using the multiresolution analysis.In this paper we provide a general method for the construction of compactly supported biorthogonal multiple wavelets by refinable function vectors which are the solutions of vector refinement equations of the form (?)(x)=(?)a(α)(?)(Mx-α),x∈Rs, where the vector of functions(?)=((?)1,...,(?)r)T is in(L2(Rs))r,a=:(a(α))α∈Zsis a finitely supported sequence of r×r matrices called the refinement mask,and M is an s×s integer matrix such that limn→∞M-n=0.Our characterizations are in the general setting and the main results of this paper are the real extensions of some known results.

  16. B Cells and Autoantibodies in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Anne-Katrin Pröbstel

    2015-07-01

    Full Text Available While over the past decades T cells have been considered key players in the pathogenesis of multiple sclerosis (MS, it has only recently become evident that B cells have a major contributing role. Our understanding of the role of B cells has evolved substantially following the clinical success of B cell-targeting therapies and increasing experimental evidence for significant B cell involvement. Rather than mere antibody-producing cells, it is becoming clear that they are team players with the capacity to prime and regulate T cells, and function both as pro- and anti-inflammatory mediators. However, despite tremendous efforts, the target antigen(s of B cells in MS have yet to be identified. The first part of this review summarizes the clinical evidence and results from animal studies pointing to the relevance of B cells in the pathogenesis of MS. The second part gives an overview of the currently known potential autoantigen targets. The third part recapitulates and critically appraises the currently available B cell-directed therapies.

  17. Composite fermions and Higgs scalars, an explanation for multiple generations

    International Nuclear Information System (INIS)

    Theories with light composite fermions are proposed as an explanation for the observation of multiple fermion generations of very different mass. It is assumed that a hypercolor interaction forms the fermion bound states at zero mass. The masses of the light composite particles are due to explicit chiral symmetry breaking by weak interactions involving vectors and Higgs scalars. In particular, we consider a simple model of Weinberg that did not have Higgs scalars, and analyze the modifications that the Higgs scalars can give. The Higgs scalars allow us to avoid his problems with massless fermions and true Goldstone bosons, and offer an explanation for the observation of large fermion mass ratios

  18. Automatic Generation of 3D Building Models with Multiple Roofs

    Institute of Scientific and Technical Information of China (English)

    Kenichi Sugihara; Yoshitugu Hayashi

    2008-01-01

    Based on building footprints (building polygons) on digital maps, we are proposing the GIS and CG integrated system that automatically generates 3D building models with multiple roofs. Most building polygons' edges meet at right angles (orthogonal polygon). The integrated system partitions orthogonal building polygons into a set of rectangles and places rectangular roofs and box-shaped building bodies on these rectangles. In order to partition an orthogonal polygon, we proposed a useful polygon expression in deciding from which vertex a dividing line is drawn. In this paper, we propose a new scheme for partitioning building polygons and show the process of creating 3D roof models.

  19. Octave-spanning supercontinuum generation via microwave frequency multiplication

    Science.gov (United States)

    Cole, D. C.; Beha, K. M.; Diddams, S. A.; Papp, S. B.

    2016-06-01

    We demonstrate a system based on telecom components for the generation of a coherent octave-spanning supercontinuum from a continuous-wave laser. The system utilizes direct multiplication of a 10 GHz signal derived from a commercial synthesizer to carve pulses from the laser, which are then iteratively chirped and compressed in two stages. After reducing the repetition rate of the resulting pulse train to 2.5 GHz using selective transmission through an electro-optic gate, propagation through highly-nonlinear fiber generates an octave-spanning supercontinuum spectrum. We discuss the impact of the noise of the modulation frequency on the coherence of the supercontinuum and discuss its mitigation. Close agreement between experiment and theory is shown throughout, and we use our ability to precisely model the experiment to propose an extension of the system to 20 GHz repetition rate.

  20. Multiplicative ARMA models to generate hourly series of global irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Mora-Lopez, L. [Universidad de Malaga (Spain). Dpto. Lenguajes y C. Computacion; Sidrach-de-Cardona, M. [Universidad de Malaga (Spain). Dpto. Fisica Aplicada

    1998-11-01

    A methodology to generate hourly series of global irradiation is proposed. The only input parameter which is required is the monthly mean value of daily global irradiation, which is available for most locations. The procedure to obtain new series is based on the use of a multiplicative autoregressive moving-average statistical model for time series with regular and seasonal components. The multiplicative nature of these models enables capture of the two types of relationships observed in recorded hourly series of global irradiation: on the one hand, the relationship between the value at one hour and the value at the previous hour; and on the other hand, the relationship between the value at one hour in one day and the value at the same hour in the previous day. In this paper the main drawback which arises when using these models to generate new series is solved: namely, the need for available recorded series in order to obtain the three parameters contained in the statistical ARMA model which is proposed (autoregressive coefficient, moving-average coefficient and variance of the error term). Specifically, expressions which enable estimation of these parameters using only monthly mean values of daily global irradiation are proposed in this paper. (author)

  1. Multiple cell and population-level interactions with mouse embryonic stem cell heterogeneity.

    Science.gov (United States)

    Cannon, Danielle; Corrigan, Adam M; Miermont, Agnes; McDonel, Patrick; Chubb, Jonathan R

    2015-08-15

    Much of development and disease concerns the generation of gene expression differences between related cells sharing similar niches. However, most analyses of gene expression only assess population and time-averaged levels of steady-state transcription. The mechanisms driving differentiation are buried within snapshots of the average cell, lacking dynamic information and the diverse regulatory history experienced by individual cells. Here, we use a quantitative imaging platform with large time series data sets to determine the regulation of developmental gene expression by cell cycle, lineage, motility and environment. We apply this technology to the regulation of the pluripotency gene Nanog in mouse embryonic stem cells. Our data reveal the diversity of cell and population-level interactions with Nanog dynamics and heterogeneity, and how this regulation responds to triggers of pluripotency. Cell cycles are highly heterogeneous and cycle time increases with Nanog reporter expression, with longer, more variable cycle times as cells approach ground-state pluripotency. Nanog reporter expression is highly stable over multiple cell generations, with fluctuations within cycles confined by an attractor state. Modelling reveals an environmental component to expression stability, in addition to any cell-autonomous behaviour, and we identify interactions of cell density with both cycle behaviour and Nanog. Rex1 expression dynamics showed shared and distinct regulatory effects. Overall, our observations of multiple partially overlapping dynamic heterogeneities imply complex cell and environmental regulation of pluripotent cell behaviour, and suggest simple deterministic views of stem cell states are inappropriate. PMID:26209649

  2. Microscope Cells Containing Multiple Micromachined Wells

    Science.gov (United States)

    Turner, Walter; Skupinski, Robert

    2003-01-01

    Tech Briefs, May 2003 19 Manufacturing Microscope Cells Containing Multiple Micromachined Wells The cost per cell has been reduced substantially. John H. Glenn Research Center, Cleveland, Ohio An improved design for multiple-well microscope cells and an associated improved method of fabricating them have been devised. [As used here, "well" denotes a cavity that has a volume of about 1 or 2 L and that is used to hold a sample for examination under a microscope. As used here, "cell" denotes a laminate, based on a standard 1- by 3-in. (2.54- by 7.62-cm) microscope slide, that comprises (1) the slide as the lower layer, (2) an intermediate layer that contains holes that serve as the wells, and (3) a top layer that either consists of, or is similar to, a standard microscope-slide cover slip.] The improved design and method of fabrication make it possible to increase (relative to a prior design and method of fabrication) the number of wells per cell while reducing the fabrication loss and reducing the cost per cell to about one-tenth of the prior value. In the prior design and method, the slide, well, and cover-slip layers were made from silicate glass. The fabrication of each cell was a labor-intensive process that included precise cutting and grinding of the glass components, fusing of the glass components, and then more grinding and polishing to obtain desired dimensions. Cells of the prior design were expensive and fragile, the rate of loss in fabrication was high, and the nature of the glass made it difficult to increase the number of cells per well. Efforts to execute alternative prior designs in plastic have not yielded satisfactory results because, for typical applications, plastics are not sufficiently thermally or chemically stable, not sufficiently optically clear, and/or not hard enough to resist scratching. The figure depicts a cell of the present improved type. The slide and cover-slip layers are made of a low-thermal-expansion glass (Pyrex(TradeMark) or

  3. Multiple actions of lysophosphatidylcholine in human Jurkat T cells

    Institute of Scientific and Technical Information of China (English)

    Young-jin IM; Yun-kyung LEE; Hae-young CHUNG; Dong-soon IM

    2006-01-01

    Aim: To obtain pathophysiological meanings of lysophosphatidylcholine (LPC) through the investigation of the effects of LPC in Jurkat T cells . Methods: We measured ROS generation, [Ca2+]i, and mitochondrial membrane potential (MMP) by fluorescent spectrometry in Jurkat T cells. Results: We observed that LPC significantly increased the reactive oxygen species (ROS) level in human Jurkat T cells. Among structurally-related lysolipids and eleven synthetic LPCs with different acyl chain lengths, palmitoyl LPC increased ROS to the highest level, α-Tocopherol, an antioxidant, and rottlerin PKCδinhibitor were inhibitory effects on LPC-induced ROS generation. LPC rapidly depolarized MMP and markedly elevated [Ca2+]i by Ca2+ influx across the plasma membrane. However, LPC-induced ROS increase seemed to not be related with LPC-induced depolarization of MMP or [Ca2+]i increase. G2A family G protein-coupled receptors (GPCR) for lysolipids were expressed in Jurkat T cells, however, evidence indicated that GPCR was not involved in LPC actions. Conclusion: LPC induced several cellular changes in Jurkat T cells, including an increase of ROS generation in a PKC8-dependent and GPCR-independent manner, increase of [Ca2+]i through Ca2+ influx, and decrease of MMP. LPC-induced actions in Jurkat T cells represent novel action modes of LPC that do not involve GPCR and multiple independent changes of intracellular signaling molecules.

  4. Identify multiple myeloma stem cells: Utopia?

    Science.gov (United States)

    Saltarella, Ilaria; Lamanuzzi, Aurelia; Reale, Antonia; Vacca, Angelo; Ria, Roberto

    2015-01-26

    Multiple myeloma (MM) is a hematologic malignancy of monoclonal plasma cells which remains incurable despite recent advances in therapies. The presence of cancer stem cells (CSCs) has been demonstrated in many solid and hematologic tumors, so the idea of CSCs has been proposed for MM, even if MM CSCs have not been define yet. The existence of myeloma CSCs with clonotypic B and clonotypic non B cells was postulated by many groups. This review aims to focus on these distinct clonotypic subpopulations and on their ability to develop and sustain MM. The bone marrow microenvironment provides to MM CSCs self-renewal, survival and drug resistance thanks to the presence of normal and cancer stem cell niches. The niches and CSCs interact each other through adhesion molecules and the interplay between ligands and receptors activates stemness signaling (Hedgehog, Wnt and Notch pathways). MM CSCs are also supposed to be responsible for drug resistance that happens in three steps from the initial cancer cell homing microenvironment-mediated to development of microenvironment-independent drug resistance. In this review, we will underline all these aspects of MM CSCs. PMID:25621108

  5. NTPDase2+ cells generate lingual epithelia and papillae

    Directory of Open Access Journals (Sweden)

    Li eFeng

    2012-11-01

    Full Text Available The tongue epithelium is one of the most rapidly self-renewing tissues in adult mammals. Multiple stem cell populations are currently believed to exist in tongue epithelia. Keratin 14 (K14 positive cells differentiate into either lingual epithelia or lingual papillae, while ecto-nucleoside triphosphate diphosphohydrolase 2 (NTPDase2 is associated with neural stem cells and astrocyte-like cells ensheathing the migrating neuroblasts. Here, using a transgenic mouse expressing rtTA from the mouse NTPDase2 promoter, we generated an inducible model by treatment with Doxycycline. By immunohistochemical analysis and in situ hybridization, we found exclusive expression of NTPDase2 in lingual epithelia and lingual papillae. Using inducible genetic cell fate mapping, we further showed that the NTPDase2+ cells generated lingual papillae and epithelia in the adult tongue. Finally, building on our previously proposed paradigm of cell migration stream, a model is further described here for lingual epithelia cell genesis. In short, the current results not only extend our understanding of the cell migration stream in lingual epithelia and lingual papillae, but they also support the concept of multiple stem cell populations in lingual epithelia and papillae.

  6. Langerhans cell histiocytosis with multiple spinal involvement.

    Science.gov (United States)

    Jiang, Liang; Liu, Xiao Guang; Zhong, Wo Quan; Ma, Qing Jun; Wei, Feng; Yuan, Hui Shu; Dang, Geng Ting; Liu, Zhong Jun

    2011-11-01

    To stress the clinical and radiologic presentation and treatment outcome of Langerhans cell histiocytosis (LCH) with multiple spinal involvements. A total of 42 cases with spinal LCH were reviewed in our hospital and 5 had multifocal spinal lesions. Multiple spinal LCH has been reported in 50 cases in the literature. All cases including ours were analyzed concerning age, sex, clinical and radiologic presentation, therapy and outcome. Of our five cases, three had neurological symptom, four soft tissue involvement and three had posterior arch extension. Compiling data from the eight largest case series of the spinal LCH reveals that 27.2% multiple vertebrae lesions. In these 55 cases, there were 26 female and 29 male with the mean age of 7.4 years (range 0.2-37). A total of 182 vertebrae were involved including 28.0% in the cervical spine, 47.8% in thoracic and 24.2% in the lumbar spine. Extraspinal LCH lesion was documented in 54.2% cases, visceral involvement in 31.1% and vertebra plana in 50% cases. Paravertebral and epidural extension were not documented in most cases. Pathological diagnosis was achieved in 47 cases including 8 open spine biopsy. The treatment strategy varied depending on different hospitals. One patient died, two had recurrence and the others had no evidence of the disease with an average of 7.2 years (range 1-21) of follow-up. Asymptomatic spinal lesions could be simply observed with or without bracing and chemotherapy is justified for multiple lesions. Surgical decompression should be reserved for the uncommon cases in which neurologic compromise does not respond to radiotherapy or progresses too rapidly for radiotherapy. PMID:20496040

  7. Microfluidic fuel cells for energy generation.

    Science.gov (United States)

    Safdar, M; Jänis, J; Sánchez, S

    2016-08-01

    Sustainable energy generation is of recent interest due to a growing energy demand across the globe and increasing environmental issues caused by conventional non-renewable means of power generation. In the context of microsystems, portable electronics and lab-on-a-chip based (bio)chemical sensors would essentially require fully integrated, reliable means of power generation. Microfluidic-based fuel cells can offer unique advantages compared to conventional fuel cells such as high surface area-to-volume ratio, ease of integration, cost effectiveness and portability. Here, we summarize recent developments which utilize the potential of microfluidic devices for energy generation. PMID:27367869

  8. Generation of Multiple Metadata Formats from a Geospatial Data Repository

    Science.gov (United States)

    Hudspeth, W. B.; Benedict, K. K.; Scott, S.

    2012-12-01

    The Earth Data Analysis Center (EDAC) at the University of New Mexico is partnering with the CYBERShARE and Environmental Health Group from the Center for Environmental Resource Management (CERM), located at the University of Texas, El Paso (UTEP), the Biodiversity Institute at the University of Kansas (KU), and the New Mexico Geo- Epidemiology Research Network (GERN) to provide a technical infrastructure that enables investigation of a variety of climate-driven human/environmental systems. Two significant goals of this NASA-funded project are: a) to increase the use of NASA Earth observational data at EDAC by various modeling communities through enabling better discovery, access, and use of relevant information, and b) to expose these communities to the benefits of provenance for improving understanding and usability of heterogeneous data sources and derived model products. To realize these goals, EDAC has leveraged the core capabilities of its Geographic Storage, Transformation, and Retrieval Engine (Gstore) platform, developed with support of the NSF EPSCoR Program. The Gstore geospatial services platform provides general purpose web services based upon the REST service model, and is capable of data discovery, access, and publication functions, metadata delivery functions, data transformation, and auto-generated OGC services for those data products that can support those services. Central to the NASA ACCESS project is the delivery of geospatial metadata in a variety of formats, including ISO 19115-2/19139, FGDC CSDGM, and the Proof Markup Language (PML). This presentation details the extraction and persistence of relevant metadata in the Gstore data store, and their transformation into multiple metadata formats that are increasingly utilized by the geospatial community to document not only core library catalog elements (e.g. title, abstract, publication data, geographic extent, projection information, and database elements), but also the processing steps used to

  9. On Multiple-Input Multiple-Output OFDM with Index Modulation for Next Generation Wireless Networks

    Science.gov (United States)

    Basar, Ertugrul

    2016-08-01

    Multiple-input multiple-output orthogonal frequency division multiplexing with index modulation (MIMO-OFDM-IM) is a novel multicarrier transmission technique which has been proposed recently as an alternative to classical MIMO-OFDM. In this scheme, OFDM with index modulation (OFDM-IM) concept is combined with MIMO transmission to take advantage of the benefits of these two techniques. In this paper, we shed light on the implementation and error performance analysis of the MIMO-OFDM-IM scheme for next generation 5G wireless networks. Maximum likelihood (ML), near-ML, simple minimum mean square error (MMSE) and ordered successive interference cancellation (OSIC) based MMSE detectors of MIMO-OFDM-IM are proposed and their theoretical performance is investigated. It has been shown via extensive computer simulations that MIMO-OFDM-IM scheme provides an interesting trade-off between error performance and spectral efficiency as well as it achieves considerably better error performance than classical MIMO-OFDM using different type detectors and under realistic conditions.

  10. Treatment Options for Plasma Cell Neoplasms (Including Multiple Myeloma)

    Science.gov (United States)

    ... Treatment Health Professional Plasma Cell Neoplasms Treatment Research Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Patient Version General Information About Plasma Cell Neoplasms Go to Health Professional Version Key ...

  11. Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)

    Science.gov (United States)

    ... Treatment Health Professional Plasma Cell Neoplasms Treatment Research Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Patient Version General Information About Plasma Cell Neoplasms Go to Health Professional Version Key ...

  12. Multiple cell configuration electromagnetic vibration energy harvester

    International Nuclear Information System (INIS)

    This paper reports the design of an electromagnetic vibration energy harvester that doubles the magnitude of output power generated by the prior four-bar magnet configuration. This enhancement was achieved with minor increase in volume by 23% and mass by 30%. The new 'double cell' design utilizes an additional pair of magnets to create a secondary air gap, or cell, for a second coil to vibrate within. To further reduce the dimensions of the device, two coils were attached to one common cantilever beam. These unique features lead to improvements of 66% in output power per unit volume (power density) and 27% increase in output power per unit volume and mass (specific power density), from 0.1 to 0.17 mW cm-3 and 0.41 to 0.51 mW cm-3 kg-1 respectively. Using the ANSYS multiphysics analysis, it was determined that for the double cell harvester, adding one additional pair of magnets created a small magnetic gradient between air gaps of 0.001 T which is insignificant in terms of electromagnetic damping. An analytical model was developed to optimize the magnitude of transformation factor and magnetic field gradient within the gap.

  13. Phagocytic plasma cells in a patient with multiple myeloma

    NARCIS (Netherlands)

    P.M. Vanhagen (P.); K. de Leeuw (K.); A. Hagemeijer (Anne); B. Löwenberg (Bob)

    1995-01-01

    textabstractPhagocytosis of blood cells by malignant plasma cells in multiple myeloma is an extremely rare condition. Here we present a 39-year-old woman with multiple myeloma. Bone marrow smear showed an extensive phagocytosis of erythrocytes and platelets by myeloma cells.

  14. Synthesis of cadmium chalcogenide based quantum dots for enhanced multiple exciton generation

    OpenAIRE

    Page, Robert Christopher

    2014-01-01

    Quantum dots (QDs) have the potential to produce more than one exciton per incident photon, if the photon energy is greater than twice the band gap energy. This process of multiple exciton generation (MEG) has the potential to lead to a step change in the efficiency of solar panels, by utilising energy commonly wasted as heat in conventional solar cells. A wide range of CdSe/CdTe and CdTe/CdSe quantum dots with and without a CdS shell were synthesised with varying core sizes and shell thickne...

  15. Endoderm Generates Endothelial Cells during Liver Development

    Directory of Open Access Journals (Sweden)

    Orit Goldman

    2014-10-01

    Full Text Available Organogenesis requires expansion of the embryonic vascular plexus that migrates into developing organs through a process called angiogenesis. Mesodermal progenitors are thought to derive endothelial cells (ECs that contribute to both embryonic vasculogenesis and the subsequent organ angiogenesis. Here, we demonstrate that during development of the liver, which is an endoderm derivative, a subset of ECs is generated from FOXA2+ endoderm-derived fetal hepatoblast progenitor cells expressing KDR (VEGFR2/FLK-1. Using human and mouse embryonic stem cell models, we demonstrate that KDR+FOXA2+ endoderm cells developing in hepatic differentiation cultures generate functional ECs. This introduces the concept that ECs originate not exclusively from mesoderm but also from endoderm, supported in Foxa2 lineage-tracing mouse embryos by the identification of FOXA2+ cell-derived CD31+ ECs that integrate the vascular network of developing fetal livers.

  16. Yours, Mine, Theirs: Multiple Generations in Today's Workplace

    Science.gov (United States)

    Grotophorst, Julie

    2011-01-01

    For the first time in history, four distinct generations are sharing the same workspace. Veterans, Baby Boomers, Gen-Xers, and Generation Y (the Millennials) are all bringing very different life experiences, expectations, and value systems to the work table. How do leaders bridge the gap among these generations and provide common ground on which…

  17. High mass throughput particle generation using multiple nozzle spraying

    Energy Technology Data Exchange (ETDEWEB)

    Pui, David Y. H.; Chen, Da-Ren

    2015-06-09

    Spraying apparatus and methods that employ multiple nozzle structures for producing multiple sprays of particles, e.g., nanoparticles, for various applications, e.g., pharmaceuticals, are provided. For example, an electrospray dispensing device may include a plurality of nozzle structures, wherein each nozzle structure is separated from adjacent nozzle structures by an internozzle distance. Sprays of particles are established from the nozzle structures by creating a nonuniform electrical field between the nozzle structures and an electrode electrically isolated therefrom.

  18. High mass throughput particle generation using multiple nozzle spraying

    Science.gov (United States)

    Pui, David Y.H.; Chen, Da-Ren

    2004-07-20

    Spraying apparatus and methods that employ multiple nozzle structures for producing multiple sprays of particles, e.g., nanoparticles, for various applications, e.g., pharmaceuticals, are provided. For example, an electrospray dispensing device may include a plurality of nozzle structures, wherein each nozzle structure is separated from adjacent nozzle structures by an internozzle distance. Sprays of particles are established from the nozzle structures by creating a nonuniform electrical field between the nozzle structures and an electrode electrically isolated therefrom.

  19. Generation of pancreatic islet cells from human embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG DongHui; JIANG Wei; SHI Yan; DENG HongKui

    2009-01-01

    Efficiently obtaining functional pancreaUc islet cells derived from human embryonic stem (hES) cells not only provides great potential to solve the shortage of islets sources for type I diabetes cell therapy,but also benefits the study of the development of the human pancreas and diabetes pathology. In 2001,hES cells were reported to have the capacity to generate insulin-producing cells by spontaneous differentiation in vitro. Since then, many strategies (such as overexpression of key transcription factors,delivery of key proteins for pancreatic development, co-transplantation of differentiated hES cells along with fetal pancreas, stepwise differentiation by mimicking in vivo pancreatic development) have been employed in order to induce the differentiation of pancreatic islet cells from hES cells. Moreover, patient-specific induced pluripotent stem (iPS) cells can be generated by reprogramming somatic cells.iPS cells have characteristics similar to those of ES cells and offer a new cell source for type I diabetes cell therapy that reduces the risk of immunologic rejection. In this review, we summarize the recent progress made in the differentiation of hES and iPS cells into functional pancreatic islet cells and discuss the challenges for their future study.

  20. Generation of pancreatic islet cells from human embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Efficiently obtaining functional pancreatic islet cells derived from human embryonic stem(hES) cells not only provides great potential to solve the shortage of islets sources for type I diabetes cell therapy,but also benefits the study of the development of the human pancreas and diabetes pathology.In 2001,hES cells were reported to have the capacity to generate insulin-producing cells by spontaneous differentiation in vitro.Since then,many strategies(such as overexpression of key transcription factors,delivery of key proteins for pancreatic development,co-transplantation of differentiated hES cells along with fetal pancreas,stepwise differentiation by mimicking in vivo pancreatic development) have been employed in order to induce the differentiation of pancreatic islet cells from hES cells.Moreover,patient-specific induced pluripotent stem(iPS) cells can be generated by reprogramming somatic cells.iPS cells have characteristics similar to those of ES cells and offer a new cell source for type I diabetes cell therapy that reduces the risk of immunologic rejection.In this review,we summarize the recent progress made in the differentiation of hES and iPS cells into functional pancreatic islet cells and discuss the challenges for their future study.

  1. Fuel cell using a hydrogen generation system

    Science.gov (United States)

    Dentinger, Paul M.; Crowell, Jeffrey A. W.

    2010-10-19

    A system is described for storing and generating hydrogen and, in particular, a system for storing and generating hydrogen for use in an H.sub.2/O.sub.2 fuel cell. The hydrogen storage system uses beta particles from a beta particle emitting material to degrade an organic polymer material to release substantially pure hydrogen. In a preferred embodiment of the invention, beta particles from .sup.63Ni are used to release hydrogen from linear polyethylene.

  2. Multiple Access Techniques for Next Generation Wireless: Recent Advances and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Shree Krishna Sharma

    2016-01-01

    Full Text Available The advances in multiple access techniques has been one of the key drivers in moving from one cellular generation to another. Starting from the first generation, several multiple access techniques have been explored in different generations and various emerging multiplexing/multiple access techniques are being investigated for the next generation of cellular networks. In this context, this paper first provides a detailed review on the existing Space Division Multiple Access (SDMA related works. Subsequently, it highlights the main features and the drawbacks of various existing and emerging multiplexing/multiple access techniques. Finally, we propose a novel concept of clustered orthogonal signature division multiple access for the next generation of cellular networks. The proposed concept envisions to employ joint antenna coding in order to enhance the orthogonality of SDMA beams with the objective of enhancing the spectral efficiency of future cellular networks.

  3. Generation of Immune Inhibitory Dendritic Cells and

    Directory of Open Access Journals (Sweden)

    Abediankenari Saeid

    2009-03-01

    Full Text Available Variety of positive as well as negative regulatory signals are provided by antigen presenting cell in particular by dendritic cells. In this research, we studied the capacity of dendritic cells to expand antigen-specific T regulatory cells.We also investigated the role of TGF-beta in induction inhibitory functions of dendritic cells in mixed leukocyte reactions.Dendritic cells were generated from blood CD14+ monocytes with granulocyte-Monocyte colony stimulating factor and interleukin-4 with or without TGF-beta (TGF-β-GM-DC or GM-DC. CD4+ T cell were isolated to assess lymphocyte proliferation by lymphocyte transformation test assay and the ratio of CD4+FOXp3+ CD25+ T cells were determined by fluorescene-activated cell sorter. T cell proliferation responses in GM-DC showed a significance antigen-specific proliferative response comparing with TGFβ-GM -DC. T Cell proliferation was inhibited in co-culture system containing DC-treated TGF-β. It can be suggested that the expsansion of T regulatory by TGF-β-GM-DC provides a means for antigen specific control of unwanted immune reactions.

  4. Extremely Efficient Multiple Electron-hole Pair Generation in Carbon Nanotube Photodiodes

    Science.gov (United States)

    Gabor, Nathaniel

    2010-03-01

    The efficient generation of multiple electron-hole (e-h) pairs from a single photon could improve the efficiency of photovoltaic solar cells beyond standard thermodynamic limits [1] and has been the focus of much recent work in semiconductor nanomaterials [2,3]. In single walled carbon nanotubes (SWNTs), the small Fermi velocity and low dielectric constant suggests that electron-electron interactions are very strong and that high-energy carriers should efficiently generate e-h pairs. Here, I will discuss observations of highly efficient generation of e-h pairs due to impact excitation in SWNT p-n junction photodiodes [4]. To investigate optoelectronic transport properties of individual SWNT photodiodes, we focus a laser beam over the device while monitoring the electronic characteristics. Optical excitation into the second electronic subband E22 ˜ 2 EGAP leads to striking photocurrent steps in the device I-VSD characteristics that occur at voltage intervals of the band gap energy EGAP/ e. Spatially and spectrally resolved photocurrent combined with temperature-dependent studies suggest that these steps result from efficient generation of multiple e-h pairs from a single hot E22 carrier. We conclude that in the SWNT photodiode, a single photon with energy greater than 2EGAP is converted into multiple e-h pairs, leading to enhanced photocurrent and increased photo-conversion efficiency. [1] W. Shockley, and H. J. Queisser, Journal of Applied Physics 32, 510 (1961). [2] R. D. Schaller, and V. I. Klimov, Physical Review Letters 92 (18), 186601 (2004). [3] R. J. Ellingson, et al, Nano Letters, 5 (5), 865-871 (2005). [4] Nathaniel M. Gabor, Zhaohui Zhong, Ken Bosnick, Jiwoong Park, and Paul McEuen, Science, 325, 1367 (2009).

  5. Generation of functional organs from stem cells

    Directory of Open Access Journals (Sweden)

    Liu Yunying

    2013-01-01

    Full Text Available Abstract We are now well entering the exciting era of stem cells. Potential stem cell therapy holds great promise for the treatment of many diseases such as stroke, traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral-sclerosis, myocardial infarction, muscular dystrophy, diabetes, and etc. It is generally believed that transplantation of specific stem cells into the injured tissue to replace the lost cells is an effective way to repair the tissue. In fact, organ transplantation has been successfully practiced in clinics for liver or kidney failure. However, the severe shortage of donor organs has been a major obstacle for the expansion of organ transplantation programs. Toward that direction, generation of transplantable organs using stem cells is a desirable approach for organ replacement and would be of great interest for both basic and clinical scientists. Here we review recent progress in the field of organ generation using various methods including single adult tissue stem cells, a blastocyst complementation system, tissue decellularization/recellularization and a combination of stem cells and tissue engineering.

  6. New Drive Train Concept with Multiple High Speed Generator

    Science.gov (United States)

    Barenhorst, F.; Serowy, S.; Andrei, C.; Schelenz, R.; Jacobs, G.; Hameyer, K.

    2016-09-01

    In the research project RapidWind (financed by the German Federal Ministry for Economic Affairs and Energy under Grant 0325642) an alternative 6 MW drive train configuration with six high-speed (n = 5000 rpm) permanent magnet synchronous generators for wind turbine generators (WTG) is designed. The gearbox for this drive train concept is assembled with a six fold power split spur gear stage in the first stage, followed by six individual 1 MW geared driven generators. Switchable couplings are developed to connect and disconnect individual geared generators depending on the input power. With this drive train configuration it is possible to improve the efficiency during partial load operation, increasing the energy yield about 1.15% for an exemplary low-wind site. The focus of this paper is the investigation of the dynamic behavior of this new WTG concept. Due to the high gear ratio the inertia relationship between rotor and generator differs from conventional WT concepts, possibly leading to intensified vibration behavior. Moreover there are switching procedures added, that might also lead to vibration issues.

  7. Betulinic acid regulates generation of neuroinflammatory mediators responsible for tissue destruction in multiple sclerosis in vitro

    Institute of Scientific and Technical Information of China (English)

    Jana BLA(Z)EVSKI; Filip PETKOVI(C); Miljana MOM(C)ILOVI(C); Reinhard PASCHKE; Goran N KALUDEROVI(C); Marija MOSTARICA STOJKOVI(C); Djordje MILJKOVI(C)

    2013-01-01

    Aim:To investigate the influences of betulinic acid (BA),a triterpenoid isolated from birch bark,on neuroinflammatory mediators involved in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis in vitro.Methods:Encephalitogenic T cells were prepared from draining lymph nodes and spinal cords of Dark Agouti rats 8 to 10 d after immunization with myelin basic protein (MBP) and complete Freund's adjuvant.Macrophages were isolated from the peritoneal cavity of adult untreated rats.Astrocytes were isolated from neonatal rat brains.The cells were cultured and then treated with different agents.IFN-y,IL-17,iNOS and CXCL12 mRNA levels in the cells were analyzed with RT-PCR.iNOS and CXCL12 protein levels were detected using immunoblot.NO and ROS generation was measured using Griess reaction and flow cytometry,respectively.Results:In encephalitogenic T cells stimulated with MBP (10 μg/mL),addition of BA inhibited IL-17 and IFN-γ production in a dosedependent manner.The estimated IC50 values for IL-17 and IFN y were 11.2 and 63.8 μmol/L,respectively.When the macrophages were stimulated with LPS (10 ng/mL),addition of BA (50 μmol/L) significantly increased ROS generation,and suppressed NO generation.The astrocytes were stimulated with ConASn containing numerous inflammatory mediators,which mimicked the inflammatory milieu within CNS; addition of BA (50 μmol/L) significantly increased ROS generation,and blocked ConASn-induced increases in iNOS and CXCL12 mRNA levels,but did not affect iNOS and CXCL12 protein levels.Importantly,in both the macrophages and astrocytes,addition of BA (50 μmol/L) inhibited lipid peroxidation.Conclusion:Besides inhibiting encephalitogenic T cell cytokines and reducing NO generation,BA induces tissue-damaging ROS generation within CNS.

  8. Force propagation and force generation in cells.

    Science.gov (United States)

    Jonas, Oliver; Duschl, Claus

    2010-09-01

    Determining how forces are produced by and propagated through the cytoskeleton (CSK) of the cell is of great interest as dynamic processes of the CSK are intimately correlated with many molecular signaling pathways. We are presenting a novel approach for integrating measurements on cell elasticity, transcellular force propagation, and cellular force generation to obtain a comprehensive description of dynamic and mechanical properties of the CSK under force loading. This approach uses a combination of scanning force microscopy (SFM) and Total Internal Reflection Fluorescence (TIRF) microscopy. We apply well-defined loading schemes onto the apical cell membrane of fibroblasts using the SFM and simultaneously use TIRF microscopy to image the topography of the basal cell membrane. The locally distinct changes of shape and depth of the cytoskeletal imprints onto the basal membrane are interpreted as results of force propagation through the cytoplasm. This observation provides evidence for the tensegrity model and demonstrates the usefulness of our approach that does not depend on potentially disturbing marker compounds. We confirm that the actin network greatly determines cell stiffness and represents the substrate that mediates force transduction through the cytoplasm of the cell. The latter is an essential feature of tensegrity. Most importantly, our new finding that, both intact actin and microtubule networks are required for enabling the cell to produce work, can only be understood within the framework of the tensegrity model. We also provide, for the first time, a direct measurement of the cell's mechanical power output under compression at two femtowatts. PMID:20607861

  9. Multiple Curricula for B Cell Developmental Programming.

    Science.gov (United States)

    Rothenberg, Ellen V

    2016-09-20

    B-1 B cells differ from conventional B-2 B cells functionally, but how these differences relate to the ontogeny of these lineages has been unclear. Two recent Immunity articles, Kristiansen et al. (2016) and Montecino-Rodriguez et al. (2016), now provide insight into the origins of B-1 and B-2 B cells, revealing a multi-layered developmental program and successive waves of B cell precursors.

  10. Multiple Curricula for B Cell Developmental Programming.

    Science.gov (United States)

    Rothenberg, Ellen V

    2016-09-20

    B-1 B cells differ from conventional B-2 B cells functionally, but how these differences relate to the ontogeny of these lineages has been unclear. Two recent Immunity articles, Kristiansen et al. (2016) and Montecino-Rodriguez et al. (2016), now provide insight into the origins of B-1 and B-2 B cells, revealing a multi-layered developmental program and successive waves of B cell precursors. PMID:27653594

  11. Multiple nuclear ortholog next generation sequencing phylogeny of Daucus

    Science.gov (United States)

    Next generation sequencing is helping to solve the data insufficiency problem hindering well-resolved dominant gene phylogenies. We used Roche 454 technology to obtain DNA sequences from 93 nuclear orthologs, dispersed throughout all linkage groups of Daucus. Of these 93 orthologs, ten were designed...

  12. Generating Multiple Alternative Clusterings Via Globally Optimal Subspaces

    DEFF Research Database (Denmark)

    Dang, Xuan-Hong; Bailey, James

    2014-01-01

    for alternative clustering generation. A distinctive feature of our algorithms is their principled formulation of an objective function, facilitating the discovery of a subspace satisfying natural quality and orthogonality criteria. The first algorithm is a regularization of the Principal Components analysis...

  13. Generating a Style-adaptive Trajectory from Multiple Demonstrations

    Directory of Open Access Journals (Sweden)

    Yue Zhao

    2014-07-01

    Full Text Available Trajectory learning and generation from demonstration have been widely discussed in recent years, with promising progress made. Existing approaches, including the Gaussian Mixture Model (GMM, affine functions and Dynamic Movement Primitives (DMPs have proven their applicability to learning the features and styles of existing trajectories and generating similar trajectories that can adapt to different dynamic situations. However, in many applications, such as grasping an object, shooting a ball, etc., different goals require trajectories of different styles. An issue that must be resolved is how to reproduce a trajectory with a suitable style. In this paper, we propose a style-adaptive trajectory generation approach based on DMPs, by which the style of the reproduced trajectories can change smoothly as the new goal changes. The proposed approach first adopts a Point Distribution Model (PDM to get the principal trajectories for different styles, then learns the model of each principal trajectory independently using DMPs, and finally adapts the parameters of the trajectory model smoothly according to the new goal using an adaptive goal-to-style mechanism. This paper further discusses the application of the approach on small-sized robots for an adaptive shooting task and on a humanoid robot arm to generate motions for table tennis-playing with different styles.

  14. Internal and ancestral controls of cell-generation times

    Science.gov (United States)

    Kubitschek, H. E.

    1969-01-01

    Lateral and longitudinal correlations between related cells reveal associations between the generation times of cells for an intermediate period /three generations in bacteral cultures/. Generation times of progeny are influenced by nongenetic factors transmitted from their ancestors.

  15. ALGORITHM TO CHOOSE ENERGY GENERATION MULTIPLE ROLE STATION

    Directory of Open Access Journals (Sweden)

    Alexandru STĂNESCU

    2014-05-01

    Full Text Available This paper proposes an algorithm that is based on a complex analysis method that is used for choosing the configuration of a power station. The station generates electric energy and hydrogen, and serves a "green" highway. The elements that need to be considered are: energy efficiency, location, availability of primary energy sources in the area, investment cost, workforce, environmental impact, compatibility with existing systems, meantime between failure.

  16. Fast generation of multiple resolution instances of raster data sets

    DEFF Research Database (Denmark)

    Arge, Lars; Haverkort, Herman; Tsirogiannis, Constantinos

    2012-01-01

    of this problem. Given a raster G of √N × √N cells we first consider the problem of computing for every 2 ≤ μ ≤ √N a raster Gμ of √N/μ × √N/μ cells such that each cell of Gμ stores the average of the values of μ×μ cells of G. We describe an algorithm that solves this problem in (N) time when the handled data fit...... in the main memory of the computer. We also provide two algorithms that solve this problem in external memory, that is when the input raster is larger than the main memory. The first external algorithm is very easy to implement and requires O(sort(N)) data block transfers from/to the external memory......, and the second algorithm requires only O(scan(N)) transfers, where sort(N) and scan(N) are the number of transfers needed to sort and scan N elements, respectively. We also study a variant of the problem where instead of the full input raster we handle only a connected subregion of arbitrary shape...

  17. Multiple Effector Functions Mediated by Human Immunodeficiency Virus-Specific CD4+ T-Cell Clones

    OpenAIRE

    Norris, Philip J.; Sumaroka, Marina; Brander, Christian; Moffett, Howell F.; Boswell, Steven L.; Nguyen, Tam; Sykulev, Yuri; Walker, Bruce D; Rosenberg, Eric S.

    2001-01-01

    Mounting evidence suggests that human immunodeficiency virus type 1 (HIV-1) Gag-specific T helper cells contribute to effective antiviral control, but their functional characteristics and the precise epitopes targeted by this response remain to be defined. In this study, we generated CD4+ T-cell clones specific for Gag from HIV-1-infected persons with vigorous Gag-specific responses detectable in peripheral blood mononuclear cells. Multiple peptides containing T helper epitopes were identifie...

  18. Multiple quantum wells for passive ultra short laser pulse generation

    CERN Document Server

    Quintero-Torres, R; Rodriguez-Rodriguez, E; Stintz, Andreas; Diels, Jean-Claude

    2007-01-01

    Solid state lasers are demanding independent control in the gain media and cavity loss to achieve ultra short laser pulses using passive mode-locking. Recently, laser mode-locking is achieved with a MBE structure with multiple quantum wells, designed to achieve two functions; Bragg mirror and changes in absorption to control the cavity dynamics. The use of an AlGaAs/AlAs Bragg mirror with a 15 nm GaAs saturable absorber used in a Cr:LiSAF tuneable laser proved to be effective to produce femtosecond pulses. The use of saturable absorbers thus far is a trial and error procedure that is changing due to the correlation with more predictive procedures.

  19. Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy.

    Science.gov (United States)

    Li, Rui; Rezk, Ayman; Miyazaki, Yusei; Hilgenberg, Ellen; Touil, Hanane; Shen, Ping; Moore, Craig S; Michel, Laure; Althekair, Faisal; Rajasekharan, Sathy; Gommerman, Jennifer L; Prat, Alexandre; Fillatreau, Simon; Bar-Or, Amit

    2015-10-21

    B cells are not limited to producing protective antibodies; they also perform additional functions relevant to both health and disease. However, the relative contribution of functionally distinct B cell subsets in human disease, the signals that regulate the balance between such subsets, and which of these subsets underlie the benefits of B cell depletion therapy (BCDT) are only partially elucidated. We describe a proinflammatory, granulocyte macrophage-colony stimulating factor (GM-CSF)-expressing human memory B cell subset that is increased in frequency and more readily induced in multiple sclerosis (MS) patients compared to healthy controls. In vitro, GM-CSF-expressing B cells efficiently activated myeloid cells in a GM-CSF-dependent manner, and in vivo, BCDT resulted in a GM-CSF-dependent decrease in proinflammatory myeloid responses of MS patients. A signal transducer and activator of transcription 5 (STAT5)- and STAT6-dependent mechanism was required for B cell GM-CSF production and reciprocally regulated the generation of regulatory IL-10-expressing B cells. STAT5/6 signaling was enhanced in B cells of untreated MS patients compared with healthy controls, and B cells reemerging in patients after BCDT normalized their STAT5/6 signaling as well as their GM-CSF/IL-10 cytokine secretion ratios. The diminished proinflammatory myeloid cell responses observed after BCDT persisted even as new B cells reconstituted. These data implicate a proinflammatory B cell/myeloid cell axis in disease and underscore the rationale for selective targeting of distinct B cell populations in MS and other human autoimmune diseases. PMID:26491076

  20. A versatile method to generate multiple types of micropatterns

    CERN Document Server

    Segerer, F J; Schuster, S; Alberola, A Piera; Zahler, S; Rädler, J O

    2015-01-01

    Micropatterning techniques have become an important tool for the study of cell behavior in controlled microenvironments. As a consequence, several approaches for the creation of micropatterns have been developed in recent years. However, the diversity of substrates, coatings and complex patterns used in cell science is so great that no single existing technique is capable of fabricating designs suitable for all experimental conditions. Hence, there is a need for patterning protocols that are flexible with regard to the materials used and compatible with different patterning strategies to create more elaborate setups. In this work, we present a novel and versatile approach to micropatterning. The protocol is based on plasma treatment, protein coating, and a PLL-PEG backfill step, and produces homogeneous patterns on a variety of substrates. Protein density within the patterns can be controlled, and gradients of surface-bound protein can be formed. Moreover, by combining the method with microcontact printing, i...

  1. Suppression of multiple ion bunches and generation of monoenergetic ion beams in laser foil-plasma

    Institute of Scientific and Technical Information of China (English)

    Zhang Shan; Xie Bai-Song; Hong Xue-Ren; Wu Hai-Cheng; Aimierding Aimidula; Zhao Xue-Yan; Liu Ming-Ping

    2011-01-01

    In one-dimensional particle-in-cell simulations, this paper shows that the formation of multiple ion bunches is disadvantageous to the generation of monoenergetic ion beams and can be suppressed by choosing an optimum target thickness in the radiation pressure acceleration mechanism by a circularly polarised laser pulse. As the laser pulse becomes intense, the optimum target thickness obtained by a non-relativistic treatment is no longer adequate. Considering the relativistic Doppler-shifted pressure, it proposes a relativistic formulation to determine the optimum target thickness. The theoretical predictions agree with the simulation results well. The model is also valid for two-dimensional cases. The accelerated ion beams can be compelled to be more stable by choosing the optimum target thickness when they exhibit some unstable behaviours.

  2. The role of the fano resonance in multiple exciton generation in quantum dots

    Science.gov (United States)

    Oksengendler, B. L.; Marasulov, M. B.; Nikiforov, V. N.

    2016-02-01

    The phenomenon of interference between two pathways of electron transfer from the valence to the conduction band at a quantum dot is considered. The first way is the conventional "valence band-conduction band" transition, while the second is the transition via a virtual two-electron state on the Tamm level in a quantum dot (QD) followed by the Auger effect, which ejects one electron from the Tamm level to the conduction band. In the case of a coherent addition of these ionization pathways, the Fano resonance can take place, this leading to an increase in the coefficient of photon absorption. This results in increasing internal efficiency of light conversion and can provide a basis for increasing the efficiency of solar cells due to the phenomenon of multiple exciton generation.

  3. New Multiple-Times Programmable CMOS ROM Cell

    Science.gov (United States)

    Chung, In-Young; Jeong, Seong Yeol; Seo, Sung Min; Lee, Myungjin; Jang, Taesu; Cha, Seon-Yong; Park, Young June

    New concept of CMOS nonvolatile memory is presented with demonstration of cell implementations. The memory cell, which is a comparator basically, makes use of comparator offset for storage quantity and the FN stress phenomena for cell programming. We also propose the stress-packet operation which is the relevant programming method to finely control the offset of the memory cell. The memory cell is multiple-time programmable while it is implemented in a standard CMOS process. We fabricated the memory cell arrays of the latch comparator and demonstrated that it is rewritten several times. We also investigated the reliability of cell data retention by monitoring programmed offsets for several months.

  4. Multiple forms of atypical rearrangements generating supernumerary derivative chromosome 15

    Directory of Open Access Journals (Sweden)

    Sigman Marian

    2008-01-01

    Full Text Available Abstract Background Maternally-derived duplications that include the imprinted region on the proximal long arm of chromosome 15 underlie a complex neurobehavioral disorder characterized by cognitive impairment, seizures and a substantial risk for autism spectrum disorders1. The duplications most often take the form of a supernumerary pseudodicentric derivative chromosome 15 [der(15] that has been called inverted duplication 15 or isodicentric 15 [idic(15], although interstitial rearrangements also occur. Similar to the deletions found in most cases of Angelman and Prader Willi syndrome, the duplications appear to be mediated by unequal homologous recombination involving low copy repeats (LCR that are found clustered in the region. Five recurrent breakpoints have been described in most cases of segmental aneuploidy of chromosome 15q11-q13 and previous studies have shown that most idic(15 chromosomes arise through BP3:BP3 or BP4:BP5 recombination events. Results Here we describe four duplication chromosomes that show evidence of atypical recombination events that involve regions outside the common breakpoints. Additionally, in one patient with a mosaic complex der(15, we examined homologous pairing of chromosome 15q11-q13 alleles by FISH in a region of frontal cortex, which identified mosaicism in this tissue and also demonstrated pairing of the signals from the der(15 and the normal homologues. Conclusion Involvement of atypical BP in the generation of idic(15 chromosomes can lead to considerable structural heterogeneity.

  5. Synthesis of Voltages of Multiple Uniform PWM, Generated by Trapezoidal and Sinusoidal Functions

    Directory of Open Access Journals (Sweden)

    A. Ctryzhniou

    2013-01-01

    Full Text Available The problem of synthesis and qualitative estimation of the harmonic composition of voltages of multiple uniform PWM pulses generated by trapezoidal and sinusoidal functions is considered. Analytical expressions for PWM pulses parameters ai  and ti have been received and they can be used for program-based generation of multiple uniform PWM, determination of n-harmonic magnitude in pulse-width regulation and AC motor operation simulation.

  6. Generating Cell Targeting Aptamers for Nanotheranostics Using Cell-SELEX

    Science.gov (United States)

    Lyu, Yifan; Chen, Guang; Shangguan, Dihua; Zhang, Liqin; Wan, Shuo; Wu, Yuan; Zhang, Hui; Duan, Lian; Liu, Chao; You, Mingxu; Wang, Jie; Tan, Weihong

    2016-01-01

    Detecting and understanding changes in cell conditions on the molecular level is of great importance for the accurate diagnosis and timely therapy of diseases. Cell-based SELEX (Systematic Evolution of Ligands by EXponential enrichment), a foundational technology used to generate highly-specific, cell-targeting aptamers, has been increasingly employed in studies of molecular medicine, including biomarker discovery and early diagnosis/targeting therapy of cancer. In this review, we begin with a mechanical description of the cell-SELEX process, covering aptamer selection, identification and identification, and aptamer characterization; following this introduction is a comprehensive discussion of the potential for aptamers as targeting moieties in the construction of various nanotheranostics. Challenges and prospects for cell-SELEX and aptamer-based nanotheranostic are also discussed. PMID:27375791

  7. The Role of Regulatory T Cells and TH17 Cells in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Walter M. T. Braga

    2012-01-01

    Full Text Available The development of multiple myeloma (MM involves a series of genetic alterations and changes in the bone marrow microenvironment, favoring the growth of the tumor and failure of local immune control. Quantitative and functional alterations in CD4+ and CD8+ T cells have been described in MM. The balance between T regulatory cells (Treg and T helper (Th 17 cells represents one essential prerequisite for maintaining anti-tumor immunity in MM. Tregs play an important role in the preservation of self-tolerance and modulation of overall immune responses against infections and tumor cells. In MM patients, Tregs seem to contribute to myeloma-related immune dysfunction and targeting them could, therefore, help to restore and enhance vital immune responses. Th17 cells protect against fungal and parasitic infections and participate in inflammatory reactions and autoimmunity. The interplay of TGF-β and IL-6, expressed at high levels in the bone marrow of myeloma patients, may affect generation of Th17 cells both directly or via other pro-inflammatory cytokines and thereby modulate antitumor immune responses. A detailed analysis of the balance between Tregs and Th17 cells seems necessary in order to design more effective and less toxic modes of immunotherapy myeloma which still is an uncurable malignancy.

  8. Multiple skin tumors of indeterminate cells in an adult.

    Science.gov (United States)

    Kolde, G; Bröcker, E B

    1986-10-01

    An adult patient with multiple unusual histiocytic tumors of the skin is described. As shown by immunohistologic study, electron microscopy, and immunoelectron microscopy, the tumors represent circumscribed proliferations of the Langerhans cell-related indeterminate dendritic cells of the skin. This distinct cutaneous histiocytosis may represent a paraneoplastic syndrome.

  9. Generating multiple orbital angular momentum vortex beams using a metasurface in radio frequency domain

    Science.gov (United States)

    Yu, Shixing; Li, Long; Shi, Guangming; Zhu, Cheng; Shi, Yan

    2016-06-01

    In this paper, an electromagnetic metasurface is designed, fabricated, and experimentally demonstrated to generate multiple orbital angular momentum (OAM) vortex beams in radio frequency domain. Theoretical formula of compensated phase-shift distribution is deduced and used to design the metasurface to produce multiple vortex radio waves in different directions with different OAM modes. The prototype of a practical configuration of square-patch metasurface is designed, fabricated, and measured to validate the theoretical analysis at 5.8 GHz. The simulated and experimental results verify that multiple OAM vortex waves can be simultaneously generated by using a single electromagnetic metasurface. The proposed method paves an effective way to generate multiple OAM vortex waves in radio and microwave wireless communication applications.

  10. Multiple Exhaust Nozzle Effects on J-2X Gas Generator Outlet Impedance

    Science.gov (United States)

    Kenny, R. Jeremy; Muss, Jeffrey; Hulka, James R.; Casiano, Matthew

    2010-01-01

    The current test setup of the J-2X gas generator system uses a multiple nozzle configuration to exhaust hot gases to drive the propellant supply turbines. Combustion stability assessment of this gas generator design requires knowledge of the impedance effects the multiple nozzle configuration creates on the combustion chamber acoustic modes. Parallel work between NASA and Sierra Engineering is presented, showing two methods used to calculate the effective end impedance resulting from multiple nozzle configurations. The NASA method is a simple estimate of the effective impedance using the long wavelength approximation. Sierra Engineering has developed a more robust numerical integration method implemented in ROCCID to accommodate for multiple nozzles. Analysis using both methods are compared to J-2X gas generator test data collected over the past year.

  11. Mass cytometry analysis shows that a novel memory phenotype B cell is expanded in multiple myeloma

    OpenAIRE

    Hansmann, Leo; Blum, Lisa; Ju, Chia-Hsin; Liedtke, Michaela; Robinson, William H; Davis, Mark M.

    2015-01-01

    It would be very beneficial if the status of cancers could be determined from a blood specimen. However, peripheral blood leukocytes are very heterogeneous between individuals and thus high resolution technologies are likely required. We used cytometry by time-of-flight (CyTOF) and next generation sequencing to ask whether a plasma cell cancer (multiple myeloma) and related pre-cancerous states had any consistent effect on the peripheral blood mononuclear cell phenotypes of patients. Analysis...

  12. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Varga, Nora [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Vereb, Zoltan; Rajnavoelgyi, Eva [Department of Immunology, Medical and Health Science Centre, University of Debrecen, Debrecen (Hungary); Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Apati, Agota, E-mail: apati@kkk.org.hu [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  13. Optimization schemes for efficient multiple exciton generation and extraction in colloidal quantum dots

    Science.gov (United States)

    Damtie, Fikeraddis A.; Karki, Khadga J.; Pullerits, Tõnu; Wacker, Andreas

    2016-08-01

    Multiple exciton generation (MEG) is a process in which more than one electron hole pair is generated per absorbed photon. It allows us to increase the efficiency of solar energy harvesting. Experimental studies have shown the multiple exciton generation yield of 1.2 in isolated colloidal quantum dots. However real photoelectric devices require the extraction of electron hole pairs to electric contacts. We provide a systematic study of the corresponding quantum coherent processes including extraction and injection and show that a proper design of extraction and injection rates enhances the yield significantly up to values around 1.6.

  14. On the Generative Power of Multiple Context-Free Grammars and Macro Grammars

    Science.gov (United States)

    Seki, Hiroyuki; Kato, Yuki

    Several grammars of which generative power is between context-free grammar and context-sensitive grammar were proposed. Among them are macro grammar and tree adjoining grammar. Multiple context-free grammar is also a natural extension of context-free grammars, and is known to be stronger in its generative power than tree adjoining grammar and yet to be recognizable in polynomial time. In this paper, the generative power of several subclasses of variable-linear macro grammars and that of multiple context-free grammars are compared in details.

  15. Multiple metastatic renal cell carcinoma isolated to pancreas.

    Science.gov (United States)

    Comunoğlu, Cem; Altaca, Gülüm; Demiralay, Ebru; Moray, Gökhan

    2012-06-01

    Renal cell carcinoma (RCC) metastases to the pancreas are reported to be rare. Isolated multiple pancreatic metastases are even rarer. We report a 68-year-old asymptomatic male patient who presented with multiple metastatic nodular lesions in the pancreas demonstrated by computerized tomography 3.5 years after radical nephrectomy performed for clear cell RCC. Spleen-preserving total pancreatectomy was performed. Gross examination revealed five well-demarcated tumoral nodules in the head, body and tail of the pancreas. Histopathological examination revealed clusters of epithelial clear cells, immunohistochemically positive for CD10 and vimentin, and negative for CK19 and chromogranin, supporting a diagnosis of metastatic RCC. The patient has remained well at 29 months post-resection, in agreement with recent experience that radical resection for multiple isolated metastatic nodular lesions can achieve improved survival and better quality of life.

  16. Cell elasticity with altered cytoskeletal architectures across multiple cell types.

    Science.gov (United States)

    Grady, Martha E; Composto, Russell J; Eckmann, David M

    2016-08-01

    The cytoskeleton is primarily responsible for providing structural support, localization and transport of organelles, and intracellular trafficking. The structural support is supplied by actin filaments, microtubules, and intermediate filaments, which contribute to overall cell elasticity to varying degrees. We evaluate cell elasticity in five different cell types with drug-induced cytoskeletal derangements to probe how actin filaments and microtubules contribute to cell elasticity and whether it is conserved across cell type. Specifically, we measure elastic stiffness in primary chondrocytes, fibroblasts, endothelial cells (HUVEC), hepatocellular carcinoma cells (HUH-7), and fibrosarcoma cells (HT 1080) subjected to two cytoskeletal destabilizers: cytochalasin D and nocodazole, which disrupt actin and microtubule polymerization, respectively. Elastic stiffness is measured by atomic force microscopy (AFM) and the disruption of the cytoskeleton is confirmed using fluorescence microscopy. The two cancer cell lines showed significantly reduced elastic moduli values (~0.5kPa) when compared to the three healthy cell lines (~2kPa). Non-cancer cells whose actin filaments were disrupted using cytochalasin D showed a decrease of 60-80% in moduli values compared to untreated cells of the same origin, whereas the nocodazole-treated cells showed no change in elasticity. Overall, we demonstrate actin filaments contribute more to elastic stiffness than microtubules but this result is cell type dependent. Cancer cells behaved differently, exhibiting increased stiffness as well as stiffness variability when subjected to nocodazole. We show that disruption of microtubule dynamics affects cancer cell elasticity, suggesting therapeutic drugs targeting microtubules be monitored for significant elastic changes. PMID:26874250

  17. Myeloid cells - targets of medication in multiple sclerosis.

    Science.gov (United States)

    Mishra, Manoj K; Yong, V Wee

    2016-09-01

    Discussions of multiple sclerosis (MS) pathophysiology tend to focus on T cells and B cells of the adaptive immune response. The innate immune system is less commonly considered in this context, although dendritic cells, monocytes, macrophages and microglia - collectively referred to as myeloid cells - have prominent roles in MS pathogenesis. These populations of myeloid cells function as antigen-presenting cells and effector cells in neuroinflammation. Furthermore, a vicious cycle of interactions between T cells and myeloid cells exacerbates pathology. Several disease-modifying therapies are now available to treat MS, and insights into their mechanisms of action have largely focused on the adaptive immune system, but these therapies also have important effects on myeloid cells. In this Review, we discuss the evidence for the roles of myeloid cells in MS and the experimental autoimmune encephalomyelitis model of MS, and consider how interactions between myeloid cells and T cells and/or B cells promote MS pathology. Finally, we discuss the direct and indirect effects of existing MS medications on myeloid cells. PMID:27514287

  18. Troglitazone reverses the multiple drug resistance phenotype in cancer cells

    Directory of Open Access Journals (Sweden)

    Gerald F Davies

    2009-03-01

    Full Text Available Gerald F Davies1, Bernhard HJ Juurlink2, Troy AA Harkness11Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Canada; 2College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi ArabiaAbstract: A major problem in treating cancer is the development of drug resistance. We previously demonstrated doxorubicin (DOX resistance in K562 human leukemia cells that was associated with upregulation of glyoxalase 1 (GLO-1 and histone H3 expression. The thiazolidinedione troglitazone (TRG downregulated GLO-1 expression and further upregulated histone H3 expression and post-translational modifications in these cells, leading to a regained sensitivity to DOX. Given the pleiotropic effects of epigenetic changes in cancer development, we hypothesized that TRG may downregulate the multiple drug resistance (MDR phenotype in a variety of cancer cells. To test this, MCF7 human breast cancer cells and K562 cells were cultured in the presence of low-dose DOX to establish DOX-resistant cell lines (K562/DOX and MCF7/DOX. The MDR phenotype was confirmed by Western blot analysis of the 170 kDa P-glycoprotein (Pgp drug efflux pump multiple drug resistance protein 1 (MDR-1, and the breast cancer resistance protein (BCRP. TRG markedly decreased expression of both MDR-1 and BCRP in these cells, resulting in sensitivity to DOX. Silencing of MDR-1 expression also sensitized MCF7/DOX cells to DOX. Use of the specific and irreversible peroxisome proliferator-activated receptor gamma (PPARγ inhibitor GW9662 in the nanomolar range not only demonstrated that the action of TRG on MCF/DOX was PPARγ-independent, but indicated that PPARγ may play a role in the MDR phenotype, which is antagonized by TRG. We conclude that TRG is potentially a useful adjunct therapy in chemoresistant cancers. Keywords: chemotherapy, doxorubicin, breast cancer resistance protein-1, multiple drug resistance, multiple drug resistance protein 1

  19. Variable Speed Wind Turbine Based on Multiple Generators Drive-Train Configuration

    DEFF Research Database (Denmark)

    Deng, Fujin; Chen, Zhe

    2010-01-01

    A variable speed wind turbine is presented in this paper, where multiple permanent magnet synchronous generators (MPMSGs) drive-train configuration is employed in the wind turbine. A cascaded multilevel converter interface based on the MPMSGs is developed to synthesize a desired high ac sinusoidal...... reduce the fluctuation of the electromagnetic torque sum and results in a good performance for the MPMSGs structure. The simulation study is conducted using PSCAD/EMTDC, and the results verify the feasibility of this variable speed wind turbine based on multiple generators drive-train configuration....... output voltage, which could be directly connected to the grids. What is more, such arrangement has been made so that the output ac voltage having a selected phase angle difference among the stator windings of multiple generators. A phase angle shift strategy is proposed in this paper, which effectively...

  20. A power-efficient ultra-wideband pulse generator based on multiple PM-IM conversions

    OpenAIRE

    Lui, KS; Wong, KKY; Zhou, E.; Xu, X.

    2010-01-01

    A novel photonic generation of power-efficient ultra-wideband (UWB) pulse by incoherent summation of two asymmetric monocycle pulses with inverted polarities is experimentally demonstrated. The principles of multiple cross-phase modulations in a highly nonlinear fiber and multiple phase modulation to intensity modulation conversions in a commercially available arrayed-waveguide grating are used. The combined UWB pulse exploiting spectral efficiency of 50.59% in experiment is fully compliant w...

  1. Cell multiplication following partial enzymatic removal of surface coat.

    Science.gov (United States)

    Wyroba, E

    1978-08-01

    Treatment of Paramecium aurelia with trypsin or pronase (1 mg per 10(5) cells, at 0 to 4 degrees C) partially removes the surface coat and modifies significantly multiplication of cells. The division rate after 24 hours of cultivation is diminished approximately twice in the case of pronase-treated cells and 1.5 for tyrpsin-digested ciliates as compared with the control. On the second day the division rate increases rapidly and number of cell divisions exceeds the values observed in the control. After 72 hours of cultivation the division rate in both untreated and enzyme-treated cells is almost the same. It is concluded that the observed inhibition of cell fission results from the enzymatic removal of the surface coat--the integrity of this surface coat seems to be necessary in the process of cell division. The influence of environmental factors on the rate of growth is presented.

  2. Multiple skin cancers in a single patient: Multiple pigmented Bowen′s disease, giant basal cell carcinoma, squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ravi Saini

    2015-01-01

    Full Text Available Basal cell carcinoma (BCC and squamous cell carcinoma are the most common type of nonmelanoma skin cancers (NMSCs. Bowen′s disease (BD, a premalignant condition, has a marginal potential (3-5% to progress to invasive carcinoma. We report here a rarest of a rare case of multiple pigmented BD with overlying squamous cell cancer along with a giant neglected BCC on the scalp of a 76-year-old man. The occurrence of multiple BD and NMSC in a single patient compelled us to explore the following hypothesis: (1 The multiple precancerous and cancerous lesions can be due to common etiopathogenesis. Chronic ultraviolet exposure, immunosupresssion, human papillomavirus infection, dietary factors, and environmental factors including arsenic exposure were probed in to. (2 There is evolution of precancerous lesions into a different type of cancers in different time frame. (3 The new cancerous lesions are subsequent cancers that developed after neglected untreated primary cancer.

  3. Normalized Metadata Generation for Human Retrieval Using Multiple Video Surveillance Cameras.

    Science.gov (United States)

    Jung, Jaehoon; Yoon, Inhye; Lee, Seungwon; Paik, Joonki

    2016-01-01

    Since it is impossible for surveillance personnel to keep monitoring videos from a multiple camera-based surveillance system, an efficient technique is needed to help recognize important situations by retrieving the metadata of an object-of-interest. In a multiple camera-based surveillance system, an object detected in a camera has a different shape in another camera, which is a critical issue of wide-range, real-time surveillance systems. In order to address the problem, this paper presents an object retrieval method by extracting the normalized metadata of an object-of-interest from multiple, heterogeneous cameras. The proposed metadata generation algorithm consists of three steps: (i) generation of a three-dimensional (3D) human model; (ii) human object-based automatic scene calibration; and (iii) metadata generation. More specifically, an appropriately-generated 3D human model provides the foot-to-head direction information that is used as the input of the automatic calibration of each camera. The normalized object information is used to retrieve an object-of-interest in a wide-range, multiple-camera surveillance system in the form of metadata. Experimental results show that the 3D human model matches the ground truth, and automatic calibration-based normalization of metadata enables a successful retrieval and tracking of a human object in the multiple-camera video surveillance system. PMID:27347961

  4. CO-GENERATION AND OPERATING NETWORK CELLS

    DEFF Research Database (Denmark)

    Nielsen, John Eli

    2008-01-01

    In Denmark several thousands of generators are connected to the distribution system (10 kV and 0.4 kV). The production from these generators many times exceeds the load. The generators can be divided into two types, Wind turbines and CHP generators. These generators have one thing in common, the ...... concept in along these lines is the “Network Cell”....

  5. Germline stem cells: stems of the next generation

    OpenAIRE

    Yuan, Hebao; Yamashita, Yukiko M

    2010-01-01

    Germline stem cells (GSCs) sustain gametogenesis during the life of organisms. Recent progress has substantially extended our understanding of GSC behavior, including the mechanisms of stem cell self-renewal, asymmetric stem cell division, stem cell niches, dedifferentiation, and tissue aging. GSCs typically are highly proliferative, due to organismal requirement to produce large number of differentiated cells. While many somatic stem cells are multipotent, with potentially multiple different...

  6. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind;

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

  7. Evaluation and Comparison of Multiple Aligners for Next-Generation Sequencing Data Analysis

    OpenAIRE

    Jing Shang; Fei Zhu; Wanwipa Vongsangnak; Yifei Tang; Wenyu Zhang; Bairong Shen

    2014-01-01

    Next-generation sequencing (NGS) technology has rapidly advanced and generated the massive data volumes. To align and map the NGS data, biologists often randomly select a number of aligners without concerning their suitable feature, high performance, and high accuracy as well as sequence variations and polymorphisms existing on reference genome. This study aims to systematically evaluate and compare the capability of multiple aligners for NGS data analysis. To explore this capability, we firs...

  8. Generation of broadband spontaneous parametric fluorescence using multiple bulk nonlinear crystals

    OpenAIRE

    Okano, Masayuki; Okamoto, Ryo; TANAKA, Akira; Subashchandran, Shanthi; Takeuchi, Shigeki

    2012-01-01

    We propose a novel method for generating broadband spontaneous parametric fluorescence by using a set of bulk nonlinear crystals (NLCs). We also demonstrate this scheme experimentally. Our method employs a superposition of spontaneous parametric fluorescence spectra generated using multiple bulk NLCs. A typical bandwidth of 160 nm (73 THz) with a degenerate wavelength of 808 nm was achieved using two beta-barium-borate (BBO) crystals, whereas a typical bandwidth of 75 nm (34 THz) was realized...

  9. Alemtuzumab treatment alters circulating innate immune cells in multiple sclerosis

    Science.gov (United States)

    Ahmetspahic, Diana; Ruck, Tobias; Schulte-Mecklenbeck, Andreas; Schwarte, Kathrin; Jörgens, Silke; Scheu, Stefanie; Windhagen, Susanne; Graefe, Bettina; Melzer, Nico; Klotz, Luisa; Arolt, Volker; Wiendl, Heinz; Meuth, Sven G.

    2016-01-01

    Objective: To characterize changes in myeloid and lymphoid innate immune cells in patients with relapsing-remitting multiple sclerosis (MS) during a 6-month follow-up after alemtuzumab treatment. Methods: Circulating innate immune cells including myeloid cells and innate lymphoid cells (ILCs) were analyzed before and 6 and 12 months after onset of alemtuzumab treatment. Furthermore, a potential effect on granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)–23 production by myeloid cells and natural killer (NK) cell cytolytic activity was determined. Results: In comparison to CD4+ T lymphocytes, myeloid and lymphoid innate cell subsets of patients with MS expressed significantly lower amounts of CD52 on their cell surface. Six months after CD52 depletion, numbers of circulating plasmacytoid dendritic cells (DCs) and conventional DCs were reduced compared to baseline. GM-CSF and IL-23 production in DCs remained unchanged. Within the ILC compartment, the subset of CD56bright NK cells specifically expanded under alemtuzumab treatment, but their cytolytic activity did not change. Conclusions: Our findings demonstrate that 6 months after alemtuzumab treatment, specific DC subsets are reduced, while CD56bright NK cells expanded in patients with MS. Thus, alemtuzumab specifically restricts the DC compartment and expands the CD56bright NK cell subset with potential immunoregulatory properties in MS. We suggest that remodeling of the innate immune compartment may promote long-term efficacy of alemtuzumab and preserve immunocompetence in patients with MS. PMID:27766281

  10. AC power generation from microbial fuel cells

    Science.gov (United States)

    Lobo, Fernanda Leite; Wang, Heming; Forrestal, Casey; Ren, Zhiyong Jason

    2015-11-01

    Microbial fuel cells (MFCs) directly convert biodegradable substrates to electricity and carry good potential for energy-positive wastewater treatment. However, the low and direct current (DC) output from MFC is not usable for general electronics except small sensors, yet commercial DC-AC converters or inverters used in solar systems cannot be directly applied to MFCs. This study presents a new DC-AC converter system for MFCs that can generate alternating voltage in any desired frequency. Results show that AC power can be easily achieved in three different frequencies tested (1, 10, 60 Hz), and no energy storage layer such as capacitors was needed. The DC-AC converter efficiency was higher than 95% when powered by either individual MFCs or simple MFC stacks. Total harmonic distortion (THD) was used to investigate the quality of the energy, and it showed that the energy could be directly usable for linear electronic loads. This study shows that through electrical conversion MFCs can be potentially used in household electronics for decentralized off-grid communities.

  11. Optimal dynamic scheduling of a power generation system to satisfy multiple criteria

    DEFF Research Database (Denmark)

    Forouzbakhsh, Farshid; Deiters, Robert M.; Shoushtari Kermanshahi, Bahman

    1991-01-01

    A computer algorithm for the optimal scheduling of generators in a power system is presented and tested. The algorithm, based on goal programming, automatically and dynami cally schedules the output of each generator in the system for optimal operation. The optimal operation can take into conside......A computer algorithm for the optimal scheduling of generators in a power system is presented and tested. The algorithm, based on goal programming, automatically and dynami cally schedules the output of each generator in the system for optimal operation. The optimal operation can take...... into consideration multiple objectives such as economy, security, and reduction of pollution as well as practical constraints. To validate and test the algorithm, an example system of 5 generators, 10 busses, and 11 transmission lines is optimized for two objectives: minimal generation cost and minimal emission...

  12. Cell biological study in multiple myeloma among atomic bomb survivors

    International Nuclear Information System (INIS)

    The study was undertaken to determine differences in the expression of cell surface antigens in normal plasma cells and mature myeloma cells. The subjects were 20 patients with multiple myeloma, including 5 A-bomb survivors. Seven normal persons, four with chronic tonsillitis, one with idiopathic thrombocytopenic purpura, and two with chronic lymphadenitis served as controls. In the group of myeloma cells, 12 showed mature myeloma cells of VLA-4+/VLA-5+/MPC-1+, and the other 8 showed precursor myeloma cells of VLA-4+/VLA-5-/MPC-1-. In terms of CD56 and CD19, CD56+/CD19- were seen in 13 patients, CD56-/CD19- in 5, and CD56+/CD19+ in 2; none of the patients showed phenotype of CD56-/CD19+. In the control group, all showed VLA-4+/VLA-5+/MPC-1+/CD44+/CD56-/CD19+; phenotype of normal plasma cells was CD38++/CD56-/CD19+ alone, which was not seen in the group of mature myeloma cells. Thus, this type is considered characteristic to normal plasma cells. These findings revealed that the difference in the expression of CD56 and CD19 aids in the identification of myeloma cells from normal plasma cells. (N.K.)

  13. Inhibition of autophagy enhances apoptosis involved with intracellular ROS generation in multiple myeloma cells exposed to Oridonin%抑制自噬促进冬凌草甲素诱导的多发性骨髓瘤细胞凋亡涉及胞内ROS产生

    Institute of Scientific and Technical Information of China (English)

    曾蓉; 陈燕; 崔国惠

    2011-01-01

    目的 本实验主要研究冬凌草甲素诱导多发性骨髓瘤发生自噬、凋亡,两者之间的关系以及所涉及的相关机制.方法 利用MTT比色法检测冬凌草甲素对多发性骨髓瘤RPMI8226细胞的增殖活性影响;透视电镜观察细胞内凋亡和自噬的形态学改变;TUNEL检测细胞凋亡;分别利用以下技术检测处理后的细胞内的自噬变化:使用QDs605nm-Anti-LC3荧光探针以及免疫荧光技术定位细胞胞内LC3Ⅰ和LC3Ⅱ蛋白,利用western blot免疫印记技术检测Beclin 1蛋白表达水平;利用DCFH-DA探针以及流式细胞术检测细胞胞内ROS水平.结果 冬凌草甲素能明显抑制RPMI8226细胞增殖,其抑制作用呈时间、剂量依赖性;冬凌草甲素能同时诱发细胞凋亡、自噬和胞内ROS产生;NAC完全抑制胞内ROS产生后冬凌草甲素诱导的细胞凋亡消失;3-MA抑制自噬后,冬凌草甲素诱导的胞内ROS产生进一步增多,凋亡增多.结论 冬凌草甲素能明显抑制RPMI8226细胞增殖;冬凌草甲素同时诱发细胞凋亡和自噬;胞内ROS产生介导冬凌草甲素诱导的凋亡;凋亡为细胞死亡的主要途径,而自噬通过下调胞内ROS产生抑制凋亡.%Objective To explore the oridonin-induced apoptosis and autophagy of multiple myelomacells the relationship between them, and the involved molecular mechanisms. Methods RPM18226 cell vitality was assessed by MTT assay. The morphology of apoptosis and autophagy was observed by TEM.TUNEL assay was used to determine apoptosis. The LC3 localization and the Beclinl protein level indicating autophagy level were analyzed by immunofluorescence analysis using the QDs605nm-AntiLC3 fluorescent probe and western blot assay. The intracellular ROS generation was estimated by FCM using the uorescent probe DCFH-DA. Results Oridonin inhibited the proliferation of RPM18226 cells dose- and time-dependently. Oridonin simultaneously induced apoptosis, autophagy and intracellular ROS generation

  14. The Twenty-First Century Multiple Generation Workforce: Overlaps and Differences but Also Challenges and Benefits

    Science.gov (United States)

    Helyer, Ruth; Lee, Dionne

    2012-01-01

    Purpose: The purpose of this paper is to explore the issues around a multiple generational workforce and more specifically, the challenges and benefits for education providers and employers. Design/methodology/approach: Reviewing research papers, analysing academic texts, interrogating market intelligence and contextualising case studies, the…

  15. Hematopoietic specification from human pluripotent stem cells: current advances and challenges toward de novo generation of hematopoietic stem cells.

    Science.gov (United States)

    Slukvin, Igor I

    2013-12-12

    Significant advances in cellular reprogramming technologies and hematopoietic differentiation from human pluripotent stem cells (hPSCs) have already enabled the routine production of multiple lineages of blood cells in vitro and opened novel opportunities to study hematopoietic development, model genetic blood diseases, and manufacture immunologically matched cells for transfusion and cancer immunotherapy. However, the generation of hematopoietic cells with robust and sustained multilineage engraftment has not been achieved. Here, we highlight the recent advances in understanding the molecular and cellular pathways leading to blood development from hPSCs and discuss potential approaches that can be taken to facilitate the development of technologies for de novo production of hematopoietic stem cells.

  16. Mass cytometry analysis shows that a novel memory phenotype B cell is expanded in multiple myeloma

    Science.gov (United States)

    Hansmann, Leo; Blum, Lisa; Ju, Chia-Hsin; Liedtke, Michaela; Robinson, William H.; Davis, Mark M.

    2015-01-01

    It would be very beneficial if the status of cancers could be determined from a blood specimen. However, peripheral blood leukocytes are very heterogeneous between individuals and thus high resolution technologies are likely required. We used cytometry by time-of-flight (CyTOF) and next generation sequencing to ask whether a plasma cell cancer (multiple myeloma) and related pre-cancerous states had any consistent effect on the peripheral blood mononuclear cell phenotypes of patients. Analysis of peripheral blood samples from 13 cancer patients, 9 pre-cancer patients, and 9 healthy individuals revealed significant differences in the frequencies of the T, B, and natural killer cell compartments. Most strikingly, we identified a novel B-cell population that normally accounts for 4.0±0.7% (mean±SD) of total B cells and is up to 13-fold expanded in multiple myeloma patients with active disease. This population expressed markers previously associated with both memory (CD27+) and naïve (CD24loCD38+) phenotypes. Single-cell immunoglobulin gene sequencing showed polyclonality, indicating that these cells are not precursors to the myeloma, and somatic mutations, a characteristic of memory cells. SYK, ERK, and p38 phosphorylation responses, and the fact that most of these cells expressed isotypes other than IgM or IgD, confirmed the memory character of this population, defining it as a novel type of memory B cells. PMID:25711758

  17. A method for generation of bone marrow-derived macrophages from cryopreserved mouse bone marrow cells.

    Directory of Open Access Journals (Sweden)

    Fernanda M Marim

    Full Text Available The broad use of transgenic and gene-targeted mice has established bone marrow-derived macrophages (BMDM as important mammalian host cells for investigation of the macrophages biology. Over the last decade, extensive research has been done to determine how to freeze and store viable hematopoietic human cells; however, there is no information regarding generation of BMDM from frozen murine bone marrow (BM cells. Here, we establish a highly efficient protocol to freeze murine BM cells and further generate BMDM. Cryopreserved murine BM cells maintain their potential for BMDM differentiation for more than 6 years. We compared BMDM obtained from fresh and frozen BM cells and found that both are similarly able to trigger the expression of CD80 and CD86 in response to LPS or infection with the intracellular bacteria Legionella pneumophila. Additionally, BMDM obtained from fresh or frozen BM cells equally restrict or support the intracellular multiplication of pathogens such as L. pneumophila and the protozoan parasite Leishmania (L. amazonensis. Although further investigation are required to support the use of the method for generation of dendritic cells, preliminary experiments indicate that bone marrow-derived dendritic cells can also be generated from cryopreserved BM cells. Overall, the method described and validated herein represents a technical advance as it allows ready and easy generation of BMDM from a stock of frozen BM cells.

  18. A new method for multiple sperm cells tracking.

    Science.gov (United States)

    Imani, Yoones; Teyfouri, Niloufar; Ahmadzadeh, Mohammad Reza; Golabbakhsh, Marzieh

    2014-01-01

    Motion analysis or quality assessment of human sperm cell is great important for clinical applications of male infertility. Sperm tracking is quite complex due to cell collision, occlusion and missed detection. The aim of this study is simultaneous tracking of multiple human sperm cells. In the first step in this research, the frame difference algorithm is used for background subtraction. There are some limitations to select an appropriate threshold value since the output accuracy is strongly dependent on the selected threshold value. To eliminate this dependency, we propose an improved non-linear diffusion filtering in the time domain. Non-linear diffusion filtering is a smoothing and noise removing approach that can preserve edges in images. Many sperms that move with different speeds in different directions eventually coincide. For multiple tracking over time, an optimal matching strategy is introduced that is based on the optimization of a new cost function. A Hungarian search method is utilized to obtain the best matching for all possible candidates. The results show nearly 3.24% frame based error in dataset of videos that contain more than 1 and less than 10 sperm cells. Hence the accuracy rate was 96.76%. These results indicate the validity of the proposed algorithm to perform multiple sperms tracking. PMID:24696807

  19. From stem cell to erythroblast: regulation of red cell production at multiple levels by multiple hormones.

    Science.gov (United States)

    Lodish, Harvey; Flygare, Johan; Chou, Song

    2010-07-01

    This article reviews the regulation of production of red blood cells at several levels: (1) the ability of erythropoietin and adhesion to a fibronectin matrix to stimulate the rapid production of red cells by inducing terminal proliferation and differentiation of committed erythroid CFU-E progenitors; (2) the regulated expansion of the pool of earlier BFU-E erythroid progenitors by glucocorticoids and other factors that occurs during chronic anemia or inflammation; and (3) the expansion of thehematopoietic cell pool to produce more progenitors of all hematopoietic lineages.

  20. Targeting proliferating cell nuclear antigen and its protein interactions induces apoptosis in multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Rebekka Müller

    Full Text Available Multiple myeloma is a hematological cancer that is considered incurable despite advances in treatment strategy during the last decade. Therapies targeting single pathways are unlikely to succeed due to the heterogeneous nature of the malignancy. Proliferating cell nuclear antigen (PCNA is a multifunctional protein essential for DNA replication and repair that is often overexpressed in cancer cells. Many proteins involved in the cellular stress response interact with PCNA through the five amino acid sequence AlkB homologue 2 PCNA-interacting motif (APIM. Thus inhibiting PCNA's protein interactions may be a good strategy to target multiple pathways simultaneously. We initially found that overexpression of peptides containing the APIM sequence increases the sensitivity of cancer cells to contemporary therapeutics. Here we have designed a cell-penetrating APIM-containing peptide, ATX-101, that targets PCNA and show that it has anti-myeloma activity. We found that ATX-101 induced apoptosis in multiple myeloma cell lines and primary cancer cells, while bone marrow stromal cells and primary healthy lymphocytes were much less sensitive. ATX-101-induced apoptosis was caspase-dependent and cell cycle phase-independent. ATX-101 also increased multiple myeloma cells' sensitivity against melphalan, a DNA damaging agent commonly used for treatment of multiple myeloma. In a xenograft mouse model, ATX-101 was well tolerated and increased the anti-tumor activity of melphalan. Therefore, targeting PCNA by ATX-101 may be a novel strategy in multiple myeloma treatment.

  1. Therapeutic strategies targeting B-cells in multiple sclerosis.

    Science.gov (United States)

    Milo, Ron

    2016-07-01

    Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS) that traditionally has been considered to be mediated primarily by T-cells. Increasing evidence, however, suggests the fundamental role of B-cells in the pathogenesis of the disease. Recent strategies targeting B-cells in MS have demonstrated impressive and sometimes surprising results: B-cell depletion by monoclonal antibodies targeting the B-cell surface antigen CD20 (e.g. rituximab, ocrelizumab, ofatumumab) was shown to exert profound anti-inflammatory effect in MS with favorable risk-benefit ratio, with ocrelizumab demonstrating efficacy in both relapsing-remitting (RR) and primary-progressive (PP) MS in phase III clinical trials. Depletion of CD52 expressing T- and B-cells and monocytes by alemtuzumab resulted in impressive and durable suppression of disease activity in RRMS patients. On the other hand, strategies targeting B-cell cytokines such as atacicept resulted in increased disease activity. As our understanding of the biology of B-cells in MS is increasing, new compounds that target B-cells continue to be developed which promise to further expand the armamentarium of MS therapies and allow for more individualized therapy for patients with this complex disease.

  2. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis.

    LENUS (Irish Health Repository)

    Fletcher, J M

    2012-02-01

    Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS), which involves autoimmune responses to myelin antigens. Studies in experimental autoimmune encephalomyelitis (EAE), an animal model for MS, have provided convincing evidence that T cells specific for self-antigens mediate pathology in these diseases. Until recently, T helper type 1 (Th1) cells were thought to be the main effector T cells responsible for the autoimmune inflammation. However more recent studies have highlighted an important pathogenic role for CD4(+) T cells that secrete interleukin (IL)-17, termed Th17, but also IL-17-secreting gammadelta T cells in EAE as well as other autoimmune and chronic inflammatory conditions. This has prompted intensive study of the induction, function and regulation of IL-17-producing T cells in MS and EAE. In this paper, we review the contribution of Th1, Th17, gammadelta, CD8(+) and regulatory T cells as well as the possible development of new therapeutic approaches for MS based on manipulating these T cell subtypes.

  3. HIF-1α inhibition blocks the cross talk between multiple myeloma plasma cells and tumor microenvironment

    International Nuclear Information System (INIS)

    Multiple myeloma (MM) is a malignant disorder of post-germinal center B cells, characterized by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow (BM). The reciprocal and complex interactions that take place between the different compartments of BM and the MM cells result in tumor growth, angiogenesis, bone disease, and drug resistance. Given the importance of the BM microenvironment in MM pathogenesis, we investigated the possible involvement of Hypoxia-Inducible transcription Factor-1 alpha (HIF-1α) in the PCs-bone marrow stromal cells interplay. To test this hypothesis, we used EZN-2968, a 3rd generation antisense oligonucleotide against HIF-1α, to inhibit HIF-1α functions. Herein, we provide evidence that the interaction between MM cells and BM stromal cells is drastically reduced upon HIF-1α down-modulation. Notably, we showed that upon exposure to HIF-1α inhibitor, neither the incubation with IL-6 nor the co-culture with BM stromal cells were able to revert the anti-proliferative effect induced by EZN-2968. Moreover, we observed a down-modulation of cytokine-induced signaling cascades and a reduction of MM cells adhesion capability to the extracellular matrix proteins in EZN-2968-treated samples. Taken together, these results strongly support the concept that HIF-1α plays a critical role in the interactions between bone BM cells and PCs in Multiple Myeloma. - Highlights: • HIF-1α inhibition induces a mild apoptotic cell death. • Down-modulation of cytokine-induced signaling cascades upon HIF-1α inhibition. • Reduced interaction between MM cells and BMSCs upon HIF-1α down-modulation. • Reduced PCs adhesion to the extracellular matrix protein induced by EZN-2968. • HIF-1α inhibition may be an attractive therapeutic strategy for Multiple Myeloma

  4. HIF-1α inhibition blocks the cross talk between multiple myeloma plasma cells and tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Borsi, Enrica, E-mail: enrica.borsi2@unibo.it [Department of Experimental Diagnostic and Specialty Medicine (DIMES), “L. and A. Seràgnoli”, Bologna University School of Medicine, S. Orsola' s University Hospital (Italy); Perrone, Giulia [Fondazione IRCCS Istituto Nazionale dei Tumori, Hematology Department, Via Venezian 1, 20133 Milano (Italy); Terragna, Carolina; Martello, Marina; Zamagni, Elena; Tacchetti, Paola; Pantani, Lucia; Brioli, Annamaria; Dico, Angela Flores; Zannetti, Beatrice Anna; Rocchi, Serena; Cavo, Michele [Department of Experimental Diagnostic and Specialty Medicine (DIMES), “L. and A. Seràgnoli”, Bologna University School of Medicine, S. Orsola' s University Hospital (Italy)

    2014-11-01

    Multiple myeloma (MM) is a malignant disorder of post-germinal center B cells, characterized by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow (BM). The reciprocal and complex interactions that take place between the different compartments of BM and the MM cells result in tumor growth, angiogenesis, bone disease, and drug resistance. Given the importance of the BM microenvironment in MM pathogenesis, we investigated the possible involvement of Hypoxia-Inducible transcription Factor-1 alpha (HIF-1α) in the PCs-bone marrow stromal cells interplay. To test this hypothesis, we used EZN-2968, a 3rd generation antisense oligonucleotide against HIF-1α, to inhibit HIF-1α functions. Herein, we provide evidence that the interaction between MM cells and BM stromal cells is drastically reduced upon HIF-1α down-modulation. Notably, we showed that upon exposure to HIF-1α inhibitor, neither the incubation with IL-6 nor the co-culture with BM stromal cells were able to revert the anti-proliferative effect induced by EZN-2968. Moreover, we observed a down-modulation of cytokine-induced signaling cascades and a reduction of MM cells adhesion capability to the extracellular matrix proteins in EZN-2968-treated samples. Taken together, these results strongly support the concept that HIF-1α plays a critical role in the interactions between bone BM cells and PCs in Multiple Myeloma. - Highlights: • HIF-1α inhibition induces a mild apoptotic cell death. • Down-modulation of cytokine-induced signaling cascades upon HIF-1α inhibition. • Reduced interaction between MM cells and BMSCs upon HIF-1α down-modulation. • Reduced PCs adhesion to the extracellular matrix protein induced by EZN-2968. • HIF-1α inhibition may be an attractive therapeutic strategy for Multiple Myeloma.

  5. Probabilistic Inference on Multiple Normalized Signal Profiles from Next Generation Sequencing: Transcription Factor Binding Sites

    KAUST Repository

    Wong, Ka-Chun

    2015-04-20

    With the prevalence of chromatin immunoprecipitation (ChIP) with sequencing (ChIP-Seq) technology, massive ChIP-Seq data has been accumulated. The ChIP-Seq technology measures the genome-wide occupancy of DNA-binding proteins in vivo. It is well-known that different DNA-binding protein occupancies may result in a gene being regulated in different conditions (e.g. different cell types). To fully understand a gene\\'s function, it is essential to develop probabilistic models on multiple ChIP-Seq profiles for deciphering the gene transcription causalities. In this work, we propose and describe two probabilistic models. Assuming the conditional independence of different DNA-binding proteins\\' occupancies, the first method (SignalRanker) is developed as an intuitive method for ChIP-Seq genome-wide signal profile inference. Unfortunately, such an assumption may not always hold in some gene regulation cases. Thus, we propose and describe another method (FullSignalRanker) which does not make the conditional independence assumption. The proposed methods are compared with other existing methods on ENCODE ChIP-Seq datasets, demonstrating its regression and classification ability. The results suggest that FullSignalRanker is the best-performing method for recovering the signal ranks on the promoter and enhancer regions. In addition, FullSignalRanker is also the best-performing method for peak sequence classification. We envision that SignalRanker and FullSignalRanker will become important in the era of next generation sequencing. FullSignalRanker program is available on the following website: http://www.cs.toronto.edu/∼wkc/FullSignalRanker/ © 2015 IEEE.

  6. Holographic photolysis for multiple cell stimulation in mouse hippocampal slices.

    Directory of Open Access Journals (Sweden)

    Morad Zahid

    Full Text Available BACKGROUND: Advanced light microscopy offers sensitive and non-invasive means to image neural activity and to control signaling with photolysable molecules and, recently, light-gated channels. These approaches require precise and yet flexible light excitation patterns. For synchronous stimulation of subsets of cells, they also require large excitation areas with millisecond and micrometric resolution. We have recently developed a new method for such optical control using a phase holographic modulation of optical wave-fronts, which minimizes power loss, enables rapid switching between excitation patterns, and allows a true 3D sculpting of the excitation volumes. In previous studies we have used holographic photololysis to control glutamate uncaging on single neuronal cells. Here, we extend the use of holographic photolysis for the excitation of multiple neurons and of glial cells. METHODS/PRINCIPAL FINDINGS: The system combines a liquid crystal device for holographic patterned photostimulation, high-resolution optical imaging, the HiLo microscopy, to define the stimulated regions and a conventional Ca(2+ imaging system to detect neural activity. By means of electrophysiological recordings and calcium imaging in acute hippocampal slices, we show that the use of excitation patterns precisely tailored to the shape of multiple neuronal somata represents a very efficient way for the simultaneous excitation of a group of neurons. In addition, we demonstrate that fast shaped illumination patterns also induce reliable responses in single glial cells. CONCLUSIONS/SIGNIFICANCE: We show that the main advantage of holographic illumination is that it allows for an efficient excitation of multiple cells with a spatiotemporal resolution unachievable with other existing approaches. Although this paper focuses on the photoactivation of caged molecules, our approach will surely prove very efficient for other probes, such as light-gated channels, genetically

  7. Th17 cells in the pathogenesis of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Marek Juszczak

    2009-10-01

    Full Text Available Th17 cells are a recently described subset of T helper lymphocytes characterized by the production of IL-17 (IL-17A. Since their discovery in 2003, studies on Th17 cells have become increasingly popular among immunologists and they have emerged as key players in the pathogenesis of multiple sclerosis (MS and other autoimmune disorders traditionally attributed to Th1 cells. Murine Th17 lymphocytes differentiate from naive CD4 cells in a specific cytokine environment, which includes TGF- and IL-6 or IL-21, whereas human Th17 cell development requires TGF-, IL-1, and IL-2 in combination with IL-6, IL-21, or IL-23. Th17-related response is additionally enhanced by osteopontin, TNF, and PGE2 and suppressed by IL-25, IL-27, IL-35, and IL-10. Apart from their main cytokine, Th17 cells can also express IL-17F, IL-21, IL-22, TNF, CCL20, and, in humans, IL-26. All of these mediators may contribute to the proinflammatory action of Th17 .cells both in the clearance of various pathogens and in autoimmunity. At least some of these functions are exerted through the induction of neutrophil-recruiting chemokines (CXCL1, CXCL2, CXCL8 by IL-17. Accumulating evidence from studies on mice and humans indicates an important role of Th17 cells in mediating autoimmune neuroinflammation. This has led some immunologists to question the previously exhibited importance of Th1 cells in MS pathology. However, more recent data suggest that both these T-cell subsets are capable of inducing and promoting the disease. Further investigation is required to clarify the role of Th17 cells in the pathogenesis of MS since some of the Th17-related molecules appear as attractive targets for future therapeutic strategies

  8. Robust generation of high-fidelity entangled states for multiple atoms

    Institute of Scientific and Technical Information of China (English)

    Lin Li-Hua

    2009-01-01

    A scheme is presented for generating entangled states of multiple atoms in a cavity. In the scheme the atoms simultaneously interact with a cavity mode, with the first atom driven by two classical fields and the other atoms driven by a classical field. Our scheme is valid even if the cavity decay rate is larger than the effective coupling strength, which is important for experiment. The generation of entangled states is conditional on the detection of a photon decaying from the cavity and thus the fidelity of the entangled state is insensitive to the detection inefficiency. Furthermore, the scheme can be applied to the case with any number of atoms in principle.

  9. A multiplicative process for generating the rank-order distribution of UK election results

    CERN Document Server

    Fenner, Trevor; Loizou, George

    2016-01-01

    Human dynamics and sociophysics suggest statistical models that may explain and provide us with a better understanding of social phenomena. Here we propose a generative multiplicative decrease model that gives rise to a rank-order distribution and allows us to analyse the results of the last three UK parliamentary elections. We provide empirical evidence that the additive Weibull distribution, which can be generated from our model, is a close fit to the electoral data, offering a novel interpretation of the recent election results.

  10. A hybrid procedure for MSW generation forecasting at multiple time scales in Xiamen City, China

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Lilai, E-mail: llxu@iue.ac.cn [Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, 1799 Jimei Road, Xiamen 361021 (China); Xiamen Key Lab of Urban Metabolism, Xiamen 361021 (China); Gao, Peiqing, E-mail: peiqing15@yahoo.com.cn [Xiamen City Appearance and Environmental Sanitation Management Office, 51 Hexiangxi Road, Xiamen 361004 (China); Cui, Shenghui, E-mail: shcui@iue.ac.cn [Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, 1799 Jimei Road, Xiamen 361021 (China); Xiamen Key Lab of Urban Metabolism, Xiamen 361021 (China); Liu, Chun, E-mail: xmhwlc@yahoo.com.cn [Xiamen City Appearance and Environmental Sanitation Management Office, 51 Hexiangxi Road, Xiamen 361004 (China)

    2013-06-15

    Highlights: ► We propose a hybrid model that combines seasonal SARIMA model and grey system theory. ► The model is robust at multiple time scales with the anticipated accuracy. ► At month-scale, the SARIMA model shows good representation for monthly MSW generation. ► At medium-term time scale, grey relational analysis could yield the MSW generation. ► At long-term time scale, GM (1, 1) provides a basic scenario of MSW generation. - Abstract: Accurate forecasting of municipal solid waste (MSW) generation is crucial and fundamental for the planning, operation and optimization of any MSW management system. Comprehensive information on waste generation for month-scale, medium-term and long-term time scales is especially needed, considering the necessity of MSW management upgrade facing many developing countries. Several existing models are available but of little use in forecasting MSW generation at multiple time scales. The goal of this study is to propose a hybrid model that combines the seasonal autoregressive integrated moving average (SARIMA) model and grey system theory to forecast MSW generation at multiple time scales without needing to consider other variables such as demographics and socioeconomic factors. To demonstrate its applicability, a case study of Xiamen City, China was performed. Results show that the model is robust enough to fit and forecast seasonal and annual dynamics of MSW generation at month-scale, medium- and long-term time scales with the desired accuracy. In the month-scale, MSW generation in Xiamen City will peak at 132.2 thousand tonnes in July 2015 – 1.5 times the volume in July 2010. In the medium term, annual MSW generation will increase to 1518.1 thousand tonnes by 2015 at an average growth rate of 10%. In the long term, a large volume of MSW will be output annually and will increase to 2486.3 thousand tonnes by 2020 – 2.5 times the value for 2010. The hybrid model proposed in this paper can enable decision makers to

  11. A hybrid procedure for MSW generation forecasting at multiple time scales in Xiamen City, China

    International Nuclear Information System (INIS)

    Highlights: ► We propose a hybrid model that combines seasonal SARIMA model and grey system theory. ► The model is robust at multiple time scales with the anticipated accuracy. ► At month-scale, the SARIMA model shows good representation for monthly MSW generation. ► At medium-term time scale, grey relational analysis could yield the MSW generation. ► At long-term time scale, GM (1, 1) provides a basic scenario of MSW generation. - Abstract: Accurate forecasting of municipal solid waste (MSW) generation is crucial and fundamental for the planning, operation and optimization of any MSW management system. Comprehensive information on waste generation for month-scale, medium-term and long-term time scales is especially needed, considering the necessity of MSW management upgrade facing many developing countries. Several existing models are available but of little use in forecasting MSW generation at multiple time scales. The goal of this study is to propose a hybrid model that combines the seasonal autoregressive integrated moving average (SARIMA) model and grey system theory to forecast MSW generation at multiple time scales without needing to consider other variables such as demographics and socioeconomic factors. To demonstrate its applicability, a case study of Xiamen City, China was performed. Results show that the model is robust enough to fit and forecast seasonal and annual dynamics of MSW generation at month-scale, medium- and long-term time scales with the desired accuracy. In the month-scale, MSW generation in Xiamen City will peak at 132.2 thousand tonnes in July 2015 – 1.5 times the volume in July 2010. In the medium term, annual MSW generation will increase to 1518.1 thousand tonnes by 2015 at an average growth rate of 10%. In the long term, a large volume of MSW will be output annually and will increase to 2486.3 thousand tonnes by 2020 – 2.5 times the value for 2010. The hybrid model proposed in this paper can enable decision makers to

  12. Image encryption combining multiple generating sequences controlled fractional DCT with dependent scrambling and diffusion

    Science.gov (United States)

    Liang, Yaru; Liu, Guoping; Zhou, Nanrun; Wu, Jianhua

    2015-02-01

    Based on the fractional discrete cosine transform with multiple generating sequences (MGSFrDCT) and the dependent scrambling and diffusion (DSD), an image encryption algorithm is proposed, in which the multiple-generating sequences greatly enlarge the key space of the encryption system. The real-valued output of MGSFrDCT is beneficial to storage, display and transmission of the cipher-text. During the stage of confusion and diffusion, the locations and values of all MGSFrDCT transformed coefficients change due to DSD, and the initial values and fractional orders of encryption system depend not only on the cipher keys but also on the plain-image due to introduction of a disturbance factor, which allows the encryption system to resist the known-plaintext and chosen-plaintext attacks. Experimental results demonstrate that the proposed encryption algorithm is feasible, effective and secure and able to resist common classical attacks.

  13. Variable Speed Wind Turbine Based on Multiple Generators Drive-Train Configuration

    OpenAIRE

    Deng, Fujin; Chen, Zhe

    2010-01-01

    A variable speed wind turbine is presented in this paper, where multiple permanent magnet synchronous generators (MPMSGs) drive-train configuration is employed in the wind turbine. A cascaded multilevel converter interface based on the MPMSGs is developed to synthesize a desired high ac sinusoidal output voltage, which could be directly connected to the grids. What is more, such arrangement has been made so that the output ac voltage having a selected phase angle difference among the stator w...

  14. Stationary Size Distributions of Growing Cells with Binary and Multiple Cell Division

    Science.gov (United States)

    Rading, M. M.; Engel, T. A.; Lipowsky, R.; Valleriani, A.

    2011-10-01

    Populations of unicellular organisms that grow under constant environmental conditions are considered theoretically. The size distribution of these cells is calculated analytically, both for the usual process of binary division, in which one mother cell produces always two daughter cells, and for the more complex process of multiple division, in which one mother cell can produce 2 n daughter cells with n=1,2,3,… . The latter mode of division is inspired by the unicellular algae Chlamydomonas reinhardtii. The uniform response of the whole population to different environmental conditions is encoded in the individual rates of growth and division of the cells. The analytical treatment of the problem is based on size-dependent rules for cell growth and stochastic transition processes for cell division. The comparison between binary and multiple division shows that these different division processes lead to qualitatively different results for the size distribution and the population growth rates.

  15. Fuel cells make gains in power generation market

    International Nuclear Information System (INIS)

    The ultra-low emission, highly efficient natural gas-fueled fuel cell system is beginning to penetrate the electric power generation market in the US and abroad as the fuel cell industry lowers product costs. And, even as the current market continues to grow, fuel cell companies are developing new technology with even higher levels of energy efficiency. The paper discusses fuel cell efficiency, business opportunities, work to reduce costs, and evolving fuel cell technology

  16. Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells

    DEFF Research Database (Denmark)

    Standal, Therese; Seidel, Carina; Hjertner, Øyvind;

    2002-01-01

    Multiple myeloma (MM) is a hematologic malignancy characterized by accumulation of plasma cells in the bone marrow (BM). Bone destruction is a complication of the disease and is usually associated with severe morbidity. The balance between receptor activator of nuclear factor-kappaB (NF......-kappaB) ligand and osteoprotegerin (OPG) is of major importance in bone homeostasis. We have recently shown that serum OPG levels are lower in patients with myeloma than in healthy individuals. Here we show that myeloma cells can bind, internalize, and degrade OPG, thereby providing a possible explanation...... for the lower levels of OPG in the BM of patients with MM. This process is dependent on interaction of OPG with heparan sulfates on the myeloma cells. The results suggest a novel biologic mechanism for the bone disease associated with MM and that treatment of the bone disease with OPG lacking the heparin...

  17. Enhanced biofilm distribution and cell performance of microfluidic microbial fuel cells with multiple anolyte inlets.

    Science.gov (United States)

    Yang, Yang; Ye, Dingding; Liao, Qiang; Zhang, Pengqing; Zhu, Xun; Li, Jun; Fu, Qian

    2016-05-15

    A laminar-flow controlled microfluidic microbial fuel cell (MMFC) is considered as a promising approach to be a bio-electrochemical system (BES). But poor bacterial colonization and low power generation are two severe bottlenecks to restrict its development. In this study, we reported a MMFC with multiple anolyte inlets (MMFC-MI) to enhance the biofilm formation and promote the power density of MMFCs. Voltage profiles during the inoculation process demonstrated MMFC-MI had a faster start-up process than the conventional microfluidic microbial fuel cell with one inlet (MMFC-OI). Meanwhile, benefited from the periodical replenishment of boundary layer near the electrode, a more densely-packed bacterial aggregation was observed along the flow direction and also the substantially low internal resistance for MMFC-MI. Most importantly, the output power density of MMFC-MI was the highest value among the reported µl-scale MFCs to our best knowledge. The presented MMFC-MI appears promising for bio-chip technology and extends the scope of microfluidic energy.

  18. Fuel cells for electric power generation

    International Nuclear Information System (INIS)

    After having first briefly illustrated the basic design, construction and operating principles of fuel cells, this paper assesses the progress that has been achieved to date in the development of the phosphoric acid (PAFC), molten carbonate (MCFC) and solid oxide (SOFC) fuel cells. Special attention is given to the design, performance and cost characteristics of the phosphoric acid fuel cells. For example, the paper cites the IFC/Toshiba 4.8 and 11.0 MW models, which have attained efficiencies of 37.5 and 41.0% respectively, and points out that these fuel cells, with efficiencies comparable to those of conventional poly-fuelled and combined cycle power plants, offer the advantages of compact size and better environmental compatibility with respect to the latter. However, fuel cells cannot yet compete with the lower per kWh costs of fossil fuel power plants. The paper concludes with an assessment of Italian fuel cell commercialization efforts, especially those centered around the use of methane fuelled PAFC's, and reviews the status of coordinated international research programs involving Japan, the USA and Italy

  19. Quantitative phosphoproteomics of proteasome inhibition in multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Feng Ge

    Full Text Available BACKGROUND: The proteasome inhibitor bortezomib represents an important advance in the treatment of multiple myeloma (MM. Bortezomib inhibits the activity of the 26S proteasome and induces cell death in a variety of tumor cells; however, the mechanism of cytotoxicity is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the differential phosphoproteome upon proteasome inhibition by using stable isotope labeling by amino acids in cell culture (SILAC in combination with phosphoprotein enrichment and LC-MS/MS analysis. In total 233 phosphoproteins were identified and 72 phosphoproteins showed a 1.5-fold or greater change upon bortezomib treatment. The phosphoproteins with expression alterations encompass all major protein classes, including a large number of nucleic acid binding proteins. Site-specific phosphopeptide quantitation revealed that Ser38 phosphorylation on stathmin increased upon bortezomib treatment, suggesting new mechanisms associated to bortezomib-induced apoptosis in MM cells. Further studies demonstrated that stathmin phosphorylation profile was modified in response to bortezomib treatment and the regulation of stathmin by phosphorylation at specific Ser/Thr residues participated in the cellular response induced by bortezomib. CONCLUSIONS/SIGNIFICANCE: Our systematic profiling of phosphorylation changes in response to bortezomib treatment not only advanced the global mechanistic understanding of the action of bortezomib on myeloma cells but also identified previously uncharacterized signaling proteins in myeloma cells.

  20. Multiple Modes of Cell Death Discovered in a Prokaryotic (Cyanobacterial) Endosymbiont.

    Science.gov (United States)

    Zheng, Weiwen; Rasmussen, Ulla; Zheng, Siping; Bao, Xiaodong; Chen, Bin; Gao, Yuan; Guan, Xiong; Larsson, John; Bergman, Birgitta

    2013-01-01

    Programmed cell death (PCD) is a genetically-based cell death mechanism with vital roles in eukaryotes. Although there is limited consensus on similar death mode programs in prokaryotes, emerging evidence suggest that PCD events are operative. Here we present cell death events in a cyanobacterium living endophytically in the fern Azolla microphylla, suggestive of PCD. This symbiosis is characterized by some unique traits such as a synchronized development, a vertical transfer of the cyanobacterium between plant generations, and a highly eroding cyanobacterial genome. A combination of methods was used to identify cell death modes in the cyanobacterium. Light- and electron microscopy analyses showed that the proportion of cells undergoing cell death peaked at 53.6% (average 20%) of the total cell population, depending on the cell type and host developmental stage. Biochemical markers used for early and late programmed cell death events related to apoptosis (Annexin V-EGFP and TUNEL staining assays), together with visualization of cytoskeleton alterations (FITC-phalloidin staining), showed that all cyanobacterial cell categories were affected by cell death. Transmission electron microscopy revealed four modes of cell death: apoptotic-like, autophagic-like, necrotic-like and autolytic-like. Abiotic stresses further enhanced cell death in a dose and time dependent manner. The data also suggest that dynamic changes in the peptidoglycan cell wall layer and in the cytoskeleton distribution patterns may act as markers for the various cell death modes. The presence of a metacaspase homolog (domain p20) further suggests that the death modes are genetically programmed. It is therefore concluded that multiple, likely genetically programmed, cell death modes exist in cyanobacteria, a finding that may be connected with the evolution of cell death in the plant kingdom. PMID:23822984

  1. Multiple Modes of Cell Death Discovered in a Prokaryotic (Cyanobacterial Endosymbiont.

    Directory of Open Access Journals (Sweden)

    Weiwen Zheng

    Full Text Available Programmed cell death (PCD is a genetically-based cell death mechanism with vital roles in eukaryotes. Although there is limited consensus on similar death mode programs in prokaryotes, emerging evidence suggest that PCD events are operative. Here we present cell death events in a cyanobacterium living endophytically in the fern Azolla microphylla, suggestive of PCD. This symbiosis is characterized by some unique traits such as a synchronized development, a vertical transfer of the cyanobacterium between plant generations, and a highly eroding cyanobacterial genome. A combination of methods was used to identify cell death modes in the cyanobacterium. Light- and electron microscopy analyses showed that the proportion of cells undergoing cell death peaked at 53.6% (average 20% of the total cell population, depending on the cell type and host developmental stage. Biochemical markers used for early and late programmed cell death events related to apoptosis (Annexin V-EGFP and TUNEL staining assays, together with visualization of cytoskeleton alterations (FITC-phalloidin staining, showed that all cyanobacterial cell categories were affected by cell death. Transmission electron microscopy revealed four modes of cell death: apoptotic-like, autophagic-like, necrotic-like and autolytic-like. Abiotic stresses further enhanced cell death in a dose and time dependent manner. The data also suggest that dynamic changes in the peptidoglycan cell wall layer and in the cytoskeleton distribution patterns may act as markers for the various cell death modes. The presence of a metacaspase homolog (domain p20 further suggests that the death modes are genetically programmed. It is therefore concluded that multiple, likely genetically programmed, cell death modes exist in cyanobacteria, a finding that may be connected with the evolution of cell death in the plant kingdom.

  2. Fuel cells for distributed generation in developing countries - an analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bauen, A. [Imperial College, London (United Kingdom). Centre for Energy Policy and Technology; E4tech (UK) Ltd., London (United Kingdom); Hart, D. [Imperial College, London (United Kingdom). Centre for Energy Policy and Technology; Chase, A. [E4tech (UK) Ltd., London (United Kingdom)

    2003-07-01

    Fuel cells are still in development as power generation technologies. They are potentially efficient and low-emissions power generation technologies with a wide range of applications. Their deployment world wide and in developing countries in particular could result in mitigation of future greenhouse gas emissions and possibly other environmental and social benefits. The economics of the systems and their competitiveness with other power generation systems will be heavily dependent on local costs and infrastructure. Modelling, based energy demand projection and on fuel cell demand curves derived from expert interviews, suggests that worldwide, projected future cost reductions in fuel cells could result in fuel cell penetration of up to 50% of the world distributed generation market by 2020. This penetration, coupled with the use of a mix of low-carbon fuels, such as natural gas, would result in significant avoided emissions of CO{sub 2} over the same period. Also, a comparison of the levelised costs of generation for the Philippines and South Africa suggests that some fuel cell technologies could become competitive with centralised generation within the next decade. Assuming that fuel cell durability can be demonstrated, the potential for fuel cells to be introduced into distributed generation in certain developing countries appears high, from a technical, economic and environmental perspective. (author)

  3. Generating native user interfaces for multiple devices by means of model transformation

    Institute of Scientific and Technical Information of China (English)

    Ignacio MARIN; Francisco ORTIN; German PEDROSA; Javier RODRIGUEZ

    2015-01-01

    In the last years, the types of devices used to access information systems have notably increased using different operating systems, screen sizes, interaction mechanisms, and software features. This device fragmentation is an important issue to tackle when developing native mobile service front-end applications. To address this issue, we propose the generation of native user interfaces (UIs) by means of model transformations, following the model-based user interface (MBUI) paradigm. The resulting MBUI framework, called LIZARD, generates applications for multiple target platforms. LIZARD allows the defi nition of applications at a high level of abstraction, and applies model transformations to generate the target native UI considering the specifi c features of target platforms. The generated applications follow the UI design guidelines and the architectural and design patterns specifi ed by the corresponding operating system manufacturer. The objective is not to generate generic applications following the lowest-common-denominator approach, but to follow the particular guidelines specifi ed for each target device. We present an example application modeled in LIZARD, generating different UIs for Windows Phone and two types of Android devices (smartphones and tablets).

  4. Generation maintenance scheduling based on multiple ob jectives and their relationship analysis

    Institute of Scientific and Technical Information of China (English)

    Jun-peng ZHAN; Chuang-xin GUO; Qing-hua WU; Lu-liang ZHANG; Hong-jun FU

    2014-01-01

    In a market environment of power systems, each producer pursues its maximal profit while the independent system operator is in charge of the system reliability and the minimization of the total generation cost when generating the generation maintenance scheduling (GMS). Thus, the GMS is inherently a multi-objective optimization problem as its objectives usually conflict with each other. This paper proposes a multi-objective GMS model in a market environment which includes three types of objectives, i.e., each producer’s profit, the system reliability, and the total generation cost. The GMS model has been solved by the group search optimizer with multiple producers (GSOMP) on two test systems. The simulation results show that the model is well solved by the GSOMP with a set of evenly distributed Pareto-optimal solutions obtained. The simulation results also illustrate that one producer’s profit conflicts with another one’s, that the total generation cost does not conflict with the profit of the producer possessing the cheapest units while the total generation cost conflicts with the other producers’ profits, and that the reliability objective conflicts with the other objectives.

  5. Automated Mosaicking of Multiple 3d Point Clouds Generated from a Depth Camera

    Science.gov (United States)

    Kim, H.; Yoon, W.; Kim, T.

    2016-06-01

    In this paper, we propose a method for automated mosaicking of multiple 3D point clouds generated from a depth camera. A depth camera generates depth data by using ToF (Time of Flight) method and intensity data by using intensity of returned signal. The depth camera used in this paper was a SR4000 from MESA Imaging. This camera generates a depth map and intensity map of 176 x 44 pixels. Generated depth map saves physical depth data with mm of precision. Generated intensity map contains texture data with many noises. We used texture maps for extracting tiepoints and depth maps for assigning z coordinates to tiepoints and point cloud mosaicking. There are four steps in the proposed mosaicking method. In the first step, we acquired multiple 3D point clouds by rotating depth camera and capturing data per rotation. In the second step, we estimated 3D-3D transformation relationships between subsequent point clouds. For this, 2D tiepoints were extracted automatically from the corresponding two intensity maps. They were converted into 3D tiepoints using depth maps. We used a 3D similarity transformation model for estimating the 3D-3D transformation relationships. In the third step, we converted local 3D-3D transformations into a global transformation for all point clouds with respect to a reference one. In the last step, the extent of single depth map mosaic was calculated and depth values per mosaic pixel were determined by a ray tracing method. For experiments, 8 depth maps and intensity maps were used. After the four steps, an output mosaicked depth map of 454x144 was generated. It is expected that the proposed method would be useful for developing an effective 3D indoor mapping method in future.

  6. Stabilization Of Apoptotic Cells: Generation Of Zombie Cells

    Directory of Open Access Journals (Sweden)

    José A. Sánchez Alcázar

    2015-08-01

    Stabilization of apoptotic cells can be used for reliable detection and quantification of apoptosis in cultured cells and may allow a safer administration of apoptotic cells in clinical applications. Furthermore, it opens new avenues in the functional reconstruction of apoptotic cells for longer preservation.

  7. Mechanism for multiplicity of steady states with distinct cell concentration in continuous culture of mammalian cells.

    Science.gov (United States)

    Yongky, Andrew; Lee, Jongchan; Le, Tung; Mulukutla, Bhanu Chandra; Daoutidis, Prodromos; Hu, Wei-Shou

    2015-07-01

    Continuous culture for the production of biopharmaceutical proteins offers the possibility of steady state operations and thus more consistent product quality and increased productivity. Under some conditions, multiplicity of steady states has been observed in continuous cultures of mammalian cells, wherein with the same dilution rate and feed nutrient composition, steady states with very different cell and product concentrations may be reached. At those different steady states, cells may exhibit a high glycolysis flux with high lactate production and low cell concentration, or a low glycolysis flux with low lactate and high cell concentration. These different steady states, with different cell concentration, also have different productivity. Developing a mechanistic understanding of the occurrence of steady state multiplicity and devising a strategy to steer the culture toward the desired steady state is critical. We establish a multi-scale kinetic model that integrates a mechanistic intracellular metabolic model and cell growth model in a continuous bioreactor. We show that steady state multiplicity exists in a range of dilution rate in continuous culture as a result of the bistable behavior in glycolysis. The insights from the model were used to devise strategies to guide the culture to the desired steady state in the multiple steady state region. The model provides a guideline principle in the design of continuous culture processes of mammalian cells.

  8. Detection of multiple mycoplasma infection in cell cultures by PCR

    Directory of Open Access Journals (Sweden)

    J. Timenetsky

    2006-07-01

    Full Text Available A total of 301 cell cultures from 15 laboratories were monitored for mycoplasma (Mollicutes using PCR and culture methodology. The infection was detected in the cell culture collection of 12 laboratories. PCR for Mollicutes detected these bacteria in 93 (30.9% samples. Although the infection was confirmed by culture for 69 (22.9% samples, PCR with generic primers did not detect the infection in five (5.4%. Mycoplasma species were identified with specific primers in 91 (30.2% of the 98 samples (32.6% considered to be infected. Mycoplasma hyorhinis was detected in 63.3% of the infected samples, M. arginini in 59.2%, Acholeplasma laidlawii in 20.4%, M. fermentans in 14.3%, M. orale in 11.2%, and M. salivarium in 8.2%. Sixty (61.2% samples were co-infected with more than one mycoplasma species. M. hyorhinis and M. arginini were the microorganisms most frequently found in combination, having been detected in 30 (30.6% samples and other associations including up to four species were detected in 30 other samples. Failure of the treatments used to eliminate mycoplasmas from cell cultures might be explained by the occurrence of these multiple infections. The present results indicate that the sharing of non-certified cells among laboratories may disseminate mycoplasma in cell cultures.

  9. Nestin Reporter Transgene Labels Multiple Central Nervous System Precursor Cells

    Directory of Open Access Journals (Sweden)

    Avery S. Walker

    2010-01-01

    Full Text Available Embryonic neuroepithelia and adult subventricular zone (SVZ stem and progenitor cells express nestin. We characterized a transgenic line that expresses enhanced green fluorescent protein (eGFP specified to neural tissue by the second intronic enhancer of the nestin promoter that had several novel features. During embryogenesis, the dorsal telencephalon contained many and the ventral telencephalon few eGFP+ cells. eGFP+ cells were found in postnatal and adult neurogenic regions. eGFP+ cells in the SVZ expressed multiple phenotype markers, glial fibrillary acidic protein, Dlx, and neuroblast-specific molecules suggesting the transgene is expressed through the lineage. eGFP+ cell numbers increased in the SVZ after cortical injury, suggesting this line will be useful in probing postinjury neurogenesis. In non-neurogenic regions, eGFP was strongly expressed in oligodendrocyte progenitors, but not in astrocytes, even when they were reactive. This eGFP+ mouse will facilitate studies of proliferative neuroepithelia and adult neurogenesis, as well as of parenchymal oligodendrocytes.

  10. Spontaneous generation of germline characteristics in mouse fibrosarcoma cells

    Science.gov (United States)

    Ma, Zhan; Hu, Yao; Jiang, Guoying; Hou, Jun; Liu, Ruilai; Lu, Yuan; Liu, Chunfang

    2012-10-01

    Germline/embryonic-specific genes have been found to be activated in somatic tumors. In this study, we further showed that cells functioning as germline could be present in mouse fibrosarcoma cells (L929 cell line). Early germline-like cells spontaneously appeared in L929 cells and further differentiated into oocyte-like cells. These germline-like cells can, in turn, develop into blastocyst-like structures in vitro and cause teratocarcinomas in vivo, which is consistent with natural germ cells in function. Generation of germline-like cells from somatic tumors might provide a novel way to understand why somatic cancer cells have strong features of embryonic/germline development. It is thought that the germline traits of tumors are associated with the central characteristics of malignancy, such as immortalization, invasion, migration and immune evasion. Therefore, germline-like cells in tumors might provide potential targets to tumor biology, diagnosis and therapy.

  11. Hepatic failure caused by plasma cell infiltration in multiple Myeloma

    Institute of Scientific and Technical Information of China (English)

    Fadi E Rahhal; Robert R Schade; Asha Nayak; Teresa A Coleman

    2009-01-01

    Although plasma cell infiltration is not rare in autopsy of patients with multiple myeloma (MM), it is very rarely detected in living patients. This is because MM rarely causes significant liver dysfunction that requires further evaluation. A 49-year-old man presented with acute renal failure and was diagnosed with kappa light chain MM stage ?B. Thalidomide and dexamethasone were initiated. The patient developed a continuous increase in bilirubin that led to severe cholestasis. A liver biopsy revealed plasma cell infiltration. He then rapidly progressed to liver failure and died. Treatment options are limited in MM with significant liver dysfunction.Despite new drug therapies in MM, those patients with rapidly progressive liver failure appear to have a dismal outcome.

  12. Multiple Chaotic Central Pattern Generators with Learning for Legged Locomotion and Malfunction Compensation

    DEFF Research Database (Denmark)

    Ren, Guanjiao; Chen, Weihai; Dasgupta, Sakyasingha;

    2015-01-01

    on a simulated annealing algorithm. In a normal situation, the CPGs synchronize and their dynamics are identical. With leg malfunction or disability, the CPGs lose synchronization leading to independent dynamics. In this case, the learning mechanism is applied to automatically adjust the remaining legs...... in a physical simulation of a quadruped as well as a hexapod robot and finally in a real six-legged walking machine called AMOSII. The experimental results presented here reveal that using multiple CPGs with learning is an effective approach for adaptive locomotion generation where, for instance, different body...... chaotic CPG controller has difficulties dealing with leg malfunction. Specifically, in the scenarios presented here, its movement permanently deviates from the desired trajectory. To address this problem, we extend the single chaotic CPG to multiple CPGs with learning. The learning mechanism is based...

  13. Generating and executing programs for a floating point single instruction multiple data instruction set architecture

    Science.gov (United States)

    Gschwind, Michael K

    2013-04-16

    Mechanisms for generating and executing programs for a floating point (FP) only single instruction multiple data (SIMD) instruction set architecture (ISA) are provided. A computer program product comprising a computer recordable medium having a computer readable program recorded thereon is provided. The computer readable program, when executed on a computing device, causes the computing device to receive one or more instructions and execute the one or more instructions using logic in an execution unit of the computing device. The logic implements a floating point (FP) only single instruction multiple data (SIMD) instruction set architecture (ISA), based on data stored in a vector register file of the computing device. The vector register file is configured to store both scalar and floating point values as vectors having a plurality of vector elements.

  14. Multiple single-board-computer system for the KEK positron generator control

    Science.gov (United States)

    Nakahara, Kazuo; Abe, Isamu; Enomoto, Atsushi; Otake, Yuji; Urano, Takao

    1986-06-01

    The KEK positron generator is controlled by means of a distributed microprocessor network. The control system is composed of three kinds of equipment: device controllers for the linac equipment, operation management stations and a communication network. Individual linac equipment has its own microprocessor-based controller. A multiple single board computer (SBC) system is used for communication control and for equipment surveillance; it has a database containing communication and linac equipment status information. The linac operation management that should be the most soft part in the control system, is separated from the multiple SBC system and is carried out by work-stations. The principle that every processor executes only one task is maintained throughout the control system. This made the software architecture very simple.

  15. Generation and Function of Induced Regulatory T Cells

    OpenAIRE

    Schmitt, Erica G.; Williams, Calvin B.

    2013-01-01

    CD4+ CD25+ Foxp3+ regulatory T (Treg) cells are essential to the balance between pro- and anti-inflammatory responses. There are two major subsets of Treg cells, “natural” Treg (nTreg) cells that develop in the thymus, and “induced” Treg (iTreg) cells that arise in the periphery from CD4+ Foxp3− conventional T cells and can be generated in vitro. Previous work has established that both subsets are required for immunological tolerance. Additionally, in vitro-derived iTreg cells can reestablish...

  16. Generation and function of induced regulatory T cells

    OpenAIRE

    Schmitt, Erica G.; Williams, Calvin B.

    2013-01-01

    CD4+ CD25+ Foxp3+ regulatory T (Treg) cells are essential to the balance between pro- and anti-inflammatory responses. There are two major subsets of Treg cells, natural Treg (nTreg) cells that develop in the thymus, and induced Treg (iTreg) cells that arise in the periphery from CD4+ Foxp3– conventional T (Tconv) cells and can be generated in vitro. Previous work has established that both subsets are required for immunological tolerance. Additionally, in vitro-derived iTreg cells can rees...

  17. Hamiltonian Description of Convective-cell Generation

    Energy Technology Data Exchange (ETDEWEB)

    J.A. Krommes and R.A. Kolesnikov

    2004-03-11

    The nonlinear statistical growth rate eq for convective cells driven by drift-wave (DW) interactions is studied with the aid of a covariant Hamiltonian formalism for the gyrofluid nonlinearities. A statistical energy theorem is proven that relates eq to a second functional tensor derivative of the DW energy. This generalizes to a wide class of systems of coupled partial differential equations a previous result for scalar dynamics. Applications to (i) electrostatic ion-temperature-gradient-driven modes at small ion temperature, and (ii) weakly electromagnetic collisional DW's are noted.

  18. Detection and Characterization of Circulating Tumour Cells in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Liangxuan Zhang

    2016-06-01

    Full Text Available Multiple myeloma (MM remains an incurable disease despite recent therapeutic improvements. The ability to detect and characterize MM circulating tumour cells (CTCs in peripheral blood provides an alternative to replace or augment invasive bone marrow (BM biopsies with a simple blood draw, providing real-time, clinically relevant information leading to improved disease manage‐ ment and therapy selection. Here we have developed and qualified an enrichment-free, cell-based immunofluores‐ cence MM CTC assay that utilizes an automated digital pathology algorithm to distinguish MM CTCs from white blood cells (WBCs on the basis of CD138 and CD45 expression levels, as well as a number of morphological parameters. These MM CTCs were further characterized for expression of phospho-ribosomal protein S6 (pS6 as a readout for PI3K/AKT pathway activation. Clinical feasi‐ bility of the assay was established by testing blood samples from a small cohort of patients, where we detected popu‐ lations of both CD138pos and CD138neg MM CTCs. In this study, we developed an immunofluorescent cell-based assay to detect and characterize CTCs in MM.

  19. Generating and Analyzing N-dimensional Hilbert Cell

    Institute of Scientific and Technical Information of China (English)

    FENG Yucai; LI Chenyang

    2005-01-01

    In this paper, two algorithms are presented for generating two code scan lists of an N-dimensional Hilbert cell, and a formal proof of the backward encoding algorithm is given. On the basis of the self-simi-larity properties of a Hilbert curve, this paper gives a novel algorithm for generating a static evolvement rule table through analyzing a Hilbert cell. By looking up the static evolvement rule table, the N-dimensional Hilbert mappings are efficiently implemented.

  20. Endothelial progenitor cells display clonal restriction in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Dai Kezhi

    2006-06-01

    Full Text Available Abstract Background In multiple myeloma (MM, increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI patterns in female patients by a human androgen receptor assay (HUMARA. In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization. Methods A total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (VH. Results In 11 patients, analysis of EPCs by HUMARA revealed significant skewing (≥ 77% expression of a single allele in 64% (n = 7. In 4 of these patients, XCI skewing was extreme (≥ 90% expression of a single allele. In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with VH primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5 of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status

  1. Generation of a predictive melphalan resistance index by drug screen of B-cell cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Martin Boegsted

    Full Text Available BACKGROUND: Recent reports indicate that in vitro drug screens combined with gene expression profiles (GEP of cancer cell lines may generate informative signatures predicting the clinical outcome of chemotherapy. In multiple myeloma (MM a range of new drugs have been introduced and now challenge conventional therapy including high dose melphalan. Consequently, the generation of predictive signatures for response to melphalan may have a clinical impact. The hypothesis is that melphalan screens and GEPs of B-cell cancer cell lines combined with multivariate statistics may provide predictive clinical information. MATERIALS AND METHODS: Microarray based GEPs and a melphalan growth inhibition screen of 59 cancer cell lines were downloaded from the National Cancer Institute database. Equivalent data were generated for 18 B-cell cancer cell lines. Linear discriminant analyses (LDA, sparse partial least squares (SPLS and pairwise comparisons of cell line data were used to build resistance signatures from both cell line panels. A melphalan resistance index was defined and estimated for each MM patient in a publicly available clinical data set and evaluated retrospectively by Cox proportional hazards and Kaplan-Meier survival analysis. PRINCIPAL FINDINGS: Both cell line panels performed well with respect to internal validation of the SPLS approach but only the B-cell panel was able to predict a significantly higher risk of relapse and death with increasing resistance index in the clinical data sets. The most sensitive and resistant cell lines, MOLP-2 and RPMI-8226 LR5, respectively, had high leverage, which suggests their differentially expressed genes to possess important predictive value. CONCLUSION: The present study presents a melphalan resistance index generated by analysis of a B-cell panel of cancer cell lines. However, the resistance index needs to be functionally validated and correlated to known MM biomarkers in independent data sets in order to

  2. Illuminating vitamin D effects on B cells--the multiple sclerosis perspective.

    Science.gov (United States)

    Rolf, Linda; Muris, Anne-Hilde; Hupperts, Raymond; Damoiseaux, Jan

    2016-03-01

    Vitamin D is associated with many immune-mediated disorders. In multiple sclerosis (MS) a poor vitamin D status is a major environmental factor associated with disease incidence and severity. The inflammation in MS is primarily T-cell-mediated, but increasing evidence points to an important role for B cells. This has paved the way for investigating vitamin D effects on B cells. In this review we elaborate on vitamin D interactions with antibody production, T-cell-stimulating capacity and regulatory B cells. Although in vitro plasma cell generation and expression of co-stimulatory molecules are inhibited and the function of regulatory B cells is promoted, this is not supported by in vivo data. We speculate that differences might be explained by the B-cell-Epstein-Barr virus interaction in MS, the exquisite role of germinal centres in B-cell biology, and/or in vivo interactions with other hormones and vitamins that interfere with the vitamin D pathways. Further research is warranted to illuminate this tube-versus-body paradox. PMID:26714674

  3. Ablation of coactivator Med1 switches the cell fate of dental epithelia to that generating hair.

    Directory of Open Access Journals (Sweden)

    Keigo Yoshizaki

    Full Text Available Cell fates are determined by specific transcriptional programs. Here we provide evidence that the transcriptional coactivator, Mediator 1 (Med1, is essential for the cell fate determination of ectodermal epithelia. Conditional deletion of Med1 in vivo converted dental epithelia into epidermal epithelia, causing defects in enamel organ development while promoting hair formation in the incisors. We identified multiple processes by which hairs are generated in Med1 deficient incisors: 1 dental epithelial stem cells lacking Med 1 fail to commit to the dental lineage, 2 Sox2-expressing stem cells extend into the differentiation zone and remain multi-potent due to reduced Notch1 signaling, and 3 epidermal fate is induced by calcium as demonstrated in dental epithelial cell cultures. These results demonstrate that Med1 is a master regulator in adult stem cells to govern epithelial cell fate.

  4. Generation of cardiac pacemaker cells by programming and differentiation.

    Science.gov (United States)

    Husse, Britta; Franz, Wolfgang-Michael

    2016-07-01

    A number of diseases are caused by faulty function of the cardiac pacemaker and described as "sick sinus syndrome". The medical treatment of sick sinus syndrome with electrical pacemaker implants in the diseased heart includes risks. These problems may be overcome via "biological pacemaker" derived from different adult cardiac cells or pluripotent stem cells. The generation of cardiac pacemaker cells requires the understanding of the pacing automaticity. Two characteristic phenomena the "membrane-clock" and the "Ca(2+)-clock" are responsible for the modulation of the pacemaker activity. Processes in the "membrane-clock" generating the spontaneous pacemaker firing are based on the voltage-sensitive membrane ion channel activity starting with slow diastolic depolarization and discharging in the action potential. The influence of the intracellular Ca(2+) modulating the pacemaker activity is characterized by the "Ca(2+)-clock". The generation of pacemaker cells started with the reprogramming of adult cardiac cells by targeted induction of one pacemaker function like HCN1-4 overexpression and enclosed in an activation of single pacemaker specific transcription factors. Reprogramming of adult cardiac cells with the transcription factor Tbx18 created cardiac cells with characteristic features of cardiac pacemaker cells. Another key transcription factor is Tbx3 specifically expressed in the cardiac conduction system including the sinoatrial node and sufficient for the induction of the cardiac pacemaker gene program. For a successful cell therapeutic practice, the generated cells should have all regulating mechanisms of cardiac pacemaker cells. Otherwise, the generated pacemaker cells serve only as investigating model for the fundamental research or as drug testing model for new antiarrhythmics. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  5. Generation of cardiac pacemaker cells by programming and differentiation.

    Science.gov (United States)

    Husse, Britta; Franz, Wolfgang-Michael

    2016-07-01

    A number of diseases are caused by faulty function of the cardiac pacemaker and described as "sick sinus syndrome". The medical treatment of sick sinus syndrome with electrical pacemaker implants in the diseased heart includes risks. These problems may be overcome via "biological pacemaker" derived from different adult cardiac cells or pluripotent stem cells. The generation of cardiac pacemaker cells requires the understanding of the pacing automaticity. Two characteristic phenomena the "membrane-clock" and the "Ca(2+)-clock" are responsible for the modulation of the pacemaker activity. Processes in the "membrane-clock" generating the spontaneous pacemaker firing are based on the voltage-sensitive membrane ion channel activity starting with slow diastolic depolarization and discharging in the action potential. The influence of the intracellular Ca(2+) modulating the pacemaker activity is characterized by the "Ca(2+)-clock". The generation of pacemaker cells started with the reprogramming of adult cardiac cells by targeted induction of one pacemaker function like HCN1-4 overexpression and enclosed in an activation of single pacemaker specific transcription factors. Reprogramming of adult cardiac cells with the transcription factor Tbx18 created cardiac cells with characteristic features of cardiac pacemaker cells. Another key transcription factor is Tbx3 specifically expressed in the cardiac conduction system including the sinoatrial node and sufficient for the induction of the cardiac pacemaker gene program. For a successful cell therapeutic practice, the generated cells should have all regulating mechanisms of cardiac pacemaker cells. Otherwise, the generated pacemaker cells serve only as investigating model for the fundamental research or as drug testing model for new antiarrhythmics. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel

  6. Computer generation of initial spatial distribution for cell automata

    OpenAIRE

    GuangHua Liu; WenJun Zhang

    2011-01-01

    The algorithm to generate spatial distribution patterns was developed and presented in this study. Three typical spatial distribution patterns, i.e., Poisson distribution, binomial distribution, and negative binomial distribution were included in the algorithm. The Java program was also provided. The algorithm can be used to generate initial distribution in cell automata modeling.

  7. Noise measurements for single and multiple operation of 50 kw wind turbine generators

    Science.gov (United States)

    Hubbard, H. H.; Shepherd, K. P.

    1982-01-01

    The noise characteristics of the U.S. Windpower Inc., 50 kw wind turbine generator were measured at various distances from 30 m to 1100 m and for a range of output power. The generated noise is affected by the aerodynamic wakes of the tower legs at frequencies below about 120 Hz and the blade trailing edge thickness at frequencies of about 2 kHz. Rope strakes and airfoil fairings on the legs did not result in substantial noise reductions. Sharpening the blade trailing edges near the tip was effective in reducing broad band noise near 2 kHz. For multiple machines the sound fields are superposed. A three-fold increase in number of machines (from 1 to 3) results in a predicted increase in he sound pressure level of about 5 dB. The detection threshold for 14 machines operating in a 13 - 20 mph wind is observed to be at approximately 1160 m in the downwind direction.

  8. Timing the generation of distinct retinal cells by homeobox proteins.

    Directory of Open Access Journals (Sweden)

    Sarah Decembrini

    2006-09-01

    Full Text Available The reason why different types of vertebrate nerve cells are generated in a particular sequence is still poorly understood. In the vertebrate retina, homeobox genes play a crucial role in establishing different cell identities. Here we provide evidence of a cellular clock that sequentially activates distinct homeobox genes in embryonic retinal cells, linking the identity of a retinal cell to its time of generation. By in situ expression analysis, we found that the three Xenopus homeobox genes Xotx5b, Xvsx1, and Xotx2 are initially transcribed but not translated in early retinal progenitors. Their translation requires cell cycle progression and is sequentially activated in photoreceptors (Xotx5b and bipolar cells (Xvsx1 and Xotx2. Furthermore, by in vivo lipofection of "sensors" in which green fluorescent protein translation is under control of the 3' untranslated region (UTR, we found that the 3' UTRs of Xotx5b, Xvsx1, and Xotx2 are sufficient to drive a spatiotemporal pattern of translation matching that of the corresponding proteins and consistent with the time of generation of photoreceptors (Xotx5b and bipolar cells (Xvsx1 and Xotx2. The block of cell cycle progression of single early retinal progenitors impairs their differentiation as photoreceptors and bipolar cells, but is rescued by the lipofection of Xotx5b and Xvsx1 coding sequences, respectively. This is the first evidence to our knowledge that vertebrate homeobox proteins can work as effectors of a cellular clock to establish distinct cell identities.

  9. Virtual microstructural leaf tissue generation based on cell growth modeling

    NARCIS (Netherlands)

    Abera, M.K.; Retta, M.A.; Verboven, P.; Nicolai, B.M.; Berghuijs, H.; Struik, P.

    2016-01-01

    A cell growth algorithm for virtual leaf tissue generation is presented based on the biomechanics of plant cells in tissues. The algorithm can account for typical differences in epidermal layers, palisade mesophyll layer and spongy mesophyll layer which have characteristic differences in the shap

  10. Teaching Generation Text: Using Cell Phones to Enhance Learning

    Science.gov (United States)

    Nielsen, Lisa; Webb, Willyn

    2011-01-01

    "Teaching Generation Text" shows how teachers can turn cell phones into an educational opportunity instead of an annoying distraction. With a host of innovative ideas, activities, lessons, and strategies, Nielsen and Webb offer a unique way to use students' preferred method of communication in the classroom. Cell phones can remind students to…

  11. GenNon-h: Generating multiple sequence alignments on nonhomogeneous phylogenetic trees

    Directory of Open Access Journals (Sweden)

    Kedzierska Anna M

    2012-08-01

    Full Text Available Abstract Background A number of software packages are available to generate DNA multiple sequence alignments (MSAs evolved under continuous-time Markov processes on phylogenetic trees. On the other hand, methods of simulating the DNA MSA directly from the transition matrices do not exist. Moreover, existing software restricts to the time-reversible models and it is not optimized to generate nonhomogeneous data (i.e. placing distinct substitution rates at different lineages. Results We present the first package designed to generate MSAs evolving under discrete-time Markov processes on phylogenetic trees, directly from probability substitution matrices. Based on the input model and a phylogenetic tree in the Newick format (with branch lengths measured as the expected number of substitutions per site, the algorithm produces DNA alignments of desired length. GenNon-h is publicly available for download. Conclusion The software presented here is an efficient tool to generate DNA MSAs on a given phylogenetic tree. GenNon-h provides the user with the nonstationary or nonhomogeneous phylogenetic data that is well suited for testing complex biological hypotheses, exploring the limits of the reconstruction algorithms and their robustness to such models.

  12. Generation of broadband spontaneous parametric fluorescence using multiple bulk nonlinear crystals

    CERN Document Server

    Okano, Masayuki; Tanaka, Akira; Subashchandran, Shanthi; Takeuchi, Shigeki; 10.1364/OE.20.013977

    2012-01-01

    We propose a novel method for generating broadband spontaneous parametric fluorescence by using a set of bulk nonlinear crystals (NLCs). We also demonstrate this scheme experimentally. Our method employs a superposition of spontaneous parametric fluorescence spectra generated using multiple bulk NLCs. A typical bandwidth of 160 nm (73 THz) with a degenerate wavelength of 808 nm was achieved using two beta-barium-borate (BBO) crystals, whereas a typical bandwidth of 75 nm (34 THz) was realized using a single BBO crystal. We also observed coincidence counts of generated photon pairs in a non-collinear configuration. The bandwidth could be further broadened by increasing the number of NLCs. Our demonstration suggests that a set of four BBO crystals could realize a bandwidth of approximately 215 nm (100 THz).We also discuss the stability of Hong-Ou-Mandel two-photon interference between the parametric fluorescence generated by this scheme. Our simple scheme is easy to implement with conventional NLCs and does not...

  13. Generation of broadband spontaneous parametric fluorescence using multiple bulk nonlinear crystals.

    Science.gov (United States)

    Okano, Masayuki; Okamoto, Ryo; Tanaka, Akira; Subashchandran, Shanthi; Takeuchi, Shigeki

    2012-06-18

    We propose a novel method for generating broadband spontaneous parametric fluorescence by using a set of bulk nonlinear crystals (NLCs). We also demonstrate this scheme experimentally. Our method employs a superposition of spontaneous parametric fluorescence spectra generated using multiple bulk NLCs. A typical bandwidth of 160 nm (73 THz) with a degenerate wavelength of 808 nm was achieved using two β-barium-borate (BBO) crystals, whereas a typical bandwidth of 75 nm (34 THz) was realized using a single BBO crystal. We also observed coincidence counts of generated photon pairs in a non-collinear configuration. The bandwidth could be further broadened by increasing the number of NLCs. Our demonstration suggests that a set of four BBO crystals could realize a bandwidth of approximately 215 nm (100 THz). We also discuss the stability of Hong-Ou-Mandel two-photon interference between the parametric fluorescence generated by this scheme. Our simple scheme is easy to implement with conventional NLCs and does not require special devices.

  14. Generation of broadband spontaneous parametric fluorescence using multiple bulk nonlinear crystals.

    Science.gov (United States)

    Okano, Masayuki; Okamoto, Ryo; Tanaka, Akira; Subashchandran, Shanthi; Takeuchi, Shigeki

    2012-06-18

    We propose a novel method for generating broadband spontaneous parametric fluorescence by using a set of bulk nonlinear crystals (NLCs). We also demonstrate this scheme experimentally. Our method employs a superposition of spontaneous parametric fluorescence spectra generated using multiple bulk NLCs. A typical bandwidth of 160 nm (73 THz) with a degenerate wavelength of 808 nm was achieved using two β-barium-borate (BBO) crystals, whereas a typical bandwidth of 75 nm (34 THz) was realized using a single BBO crystal. We also observed coincidence counts of generated photon pairs in a non-collinear configuration. The bandwidth could be further broadened by increasing the number of NLCs. Our demonstration suggests that a set of four BBO crystals could realize a bandwidth of approximately 215 nm (100 THz). We also discuss the stability of Hong-Ou-Mandel two-photon interference between the parametric fluorescence generated by this scheme. Our simple scheme is easy to implement with conventional NLCs and does not require special devices. PMID:22714463

  15. Generating free charges by carrier multiplication in quantum dots for highly efficient photovoltaics.

    Science.gov (United States)

    Ten Cate, Sybren; Sandeep, C S Suchand; Liu, Yao; Law, Matt; Kinge, Sachin; Houtepen, Arjan J; Schins, Juleon M; Siebbeles, Laurens D A

    2015-02-17

    CONSPECTUS: In a conventional photovoltaic device (solar cell or photodiode) photons are absorbed in a bulk semiconductor layer, leading to excitation of an electron from a valence band to a conduction band. Directly after photoexcitation, the hole in the valence band and the electron in the conduction band have excess energy given by the difference between the photon energy and the semiconductor band gap. In a bulk semiconductor, the initially hot charges rapidly lose their excess energy as heat. This heat loss is the main reason that the theoretical efficiency of a conventional solar cell is limited to the Shockley-Queisser limit of ∼33%. The efficiency of a photovoltaic device can be increased if the excess energy is utilized to excite additional electrons across the band gap. A sufficiently hot charge can produce an electron-hole pair by Coulomb scattering on a valence electron. This process of carrier multiplication (CM) leads to formation of two or more electron-hole pairs for the absorption of one photon. In bulk semiconductors such as silicon, the energetic threshold for CM is too high to be of practical use. However, CM in nanometer sized semiconductor quantum dots (QDs) offers prospects for exploitation in photovoltaics. CM leads to formation of two or more electron-hole pairs that are initially in close proximity. For photovoltaic applications, these charges must escape from recombination. This Account outlines our recent progress in the generation of free mobile charges that result from CM in QDs. Studies of charge carrier photogeneration and mobility were carried out using (ultrafast) time-resolved laser techniques with optical or ac conductivity detection. We found that charges can be extracted from photoexcited PbS QDs by bringing them into contact with organic electron and hole accepting materials. However, charge localization on the QD produces a strong Coulomb attraction to its counter charge in the organic material. This limits the production

  16. CML Mouse Model Generated from Leukemia Stem Cells.

    Science.gov (United States)

    Hu, Yiguo

    2016-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder with a high number of well-differentiated neutrophils in peripheral blood and myeloid cells in bone marrow (BM). CML is derived from the hematopoietic stem cells (HSCs) with the Philadelphia chromosome (Ph(+), t(9;22)-(q34;q11)), resulting in generating a fusion oncogene, BCR/ABL1. HSCs with Ph(+) are defined as leukemia stem cells (LSCs), a subpopulation cell at the apex of hierarchies in leukemia cells and responsible for the disease continuous propagation. Several kinds of CML models have been developed to reveal the mechanism of CML pathogenesis and evaluate therapeutic drugs in the past three decades. Here, we describe the procedures to generate a CML mouse model by introducing BCR/ABL1 into Lin(-)Sca1(+) cKit(+) population cells purified from mouse bone marrow. In CML retroviral transduction/transplantation mouse models, this modified model can mimic CML pathogenesis on high fidelity. PMID:27581136

  17. Efficiency dip observed with InGaN-based multiple quantum well solar cells

    KAUST Repository

    Lai, Kunyu

    2014-01-01

    The dip of external quantum efficiency (EQE) is observed on In0.15Ga0.85N/GaN multiple quantum well (MQW) solar cells upon the increase of incident optical power density. With indium composition increased to 25%, the EQE dip becomes much less noticeable. The composition dependence of EQE dip is ascribed to the competition between radiative recombination and photocurrent generation in the active region, which are dictated by quantum-confined Stark effect (QCSE) and composition fluctuation in the MQWs.

  18. Multiple-octave spanning mid-IR supercontinuum generation in bulk quadratic nonlinear crystals

    CERN Document Server

    Zhou, Binbin

    2016-01-01

    Bright and broadband coherent mid-IR radiation is important for exciting and probing molecular vibrations. Using cascaded nonlinearities in conventional quadratic nonlinear crystal like lithium niobate, self-defocusing near-IR solitons have been demonstrated that led to very broadband supercontinuum generation in the visible, near-IR and short-wavelength mid-IR. Here we conduct an experiment where a mid-IR crystal pumped in the mid-IR gives multiple-octave spanning supercontinua. The crystal is cut for noncritical interaction, so the three-wave mixing of a single mid-IR femtosecond pump source leads to highly phase-mismatched second-harmonic generation. This self-acting cascaded process leads to the formation of a self-defocusing soliton at the mid-IR pump wavelength and after the self-compression point multiple octave-spanning supercontinua are observed (covering 1.6-$7.0~\\mu$m). The results were recorded in a commercially available crystal LiInS$_2$ pumped in the 3-$4~\\mu$m range, but other mid-IR crystals ...

  19. Generation of antigen-specific T cell immunity through T cell receptor gene transfer

    NARCIS (Netherlands)

    Coccoris, Miriam

    2009-01-01

    Cancer cells often escape the attack of immune cells because they originate from self-tissue. Through T cell receptor gene transfer it is possible to equip peripheral T cells with a desired specificity, and this strategy may be useful to generate tumor-specific T cells for the treatment of cancer in

  20. Generation and characterization of human insulin-releasing cell lines

    OpenAIRE

    Joffé Elisa; Machado Marcel CC; Buchanan Cecilia; Terra Letícia F; Stigliano Iván; Krogh Karin; Peters Maria G; Labriola Leticia; Puricelli Lydia; Sogayar Mari C

    2009-01-01

    Abstract Background The in vitro culture of insulinomas provides an attractive tool to study cell proliferation and insulin synthesis and secretion. However, only a few human beta cell lines have been described, with long-term passage resulting in loss of insulin secretion. Therefore, we set out to establish and characterize human insulin-releasing cell lines. Results We generated ex-vivo primary cultures from two independent human insulinomas and from a human nesidioblastosis, all of which w...

  1. Extrathymically generated regulatory T cells control mucosal Th2 inflammation

    OpenAIRE

    Josefowicz, Steven Z.; Niec, Rachel E.; Kim, Hye Young; Treuting, Piper; Chinen, Takatoshi; Zheng, Ye; Umetsu, Dale T.; Rudensky, Alexander Y.

    2012-01-01

    A balance between pro- and anti-inflammatory mechanisms at mucosal interfaces, sites of constitutive exposure to microbes and non-microbial foreign substances, allows for efficient protection against pathogens yet prevents adverse inflammatory responses associated with allergy, asthma, and intestinal inflammation1. Regulatory T (Treg) cells prevent systemic and tissue-specific autoimmunity and inflammatory lesions at mucosal interfaces. These cells are generated in the thymus (tTreg cells) an...

  2. Generation of avian cells resembling osteoclasts from mononuclear phagocytes

    Science.gov (United States)

    Alvarez, J. I.; Teitelbaum, S. L.; Blair, H. C.; Greenfield, E. M.; Athanasou, N. A.; Ross, F. P.

    1991-01-01

    Several lines of indirect evidence suggest that a monocyte family precursor gives rise to the osteoclast, although this hypothesis is controversial. Starting with a uniform population of nonspecific esterase positive, tartrate-sensitive, acid phosphatase-producing, mannose receptor-bearing mononuclear cells, prepared from dispersed marrow of calcium-deprived laying hens by cell density separation and selective cellular adherence, we generated multinucleated cells in vitro. When cultured with devitalized bone, these cells show, by electron microscopy, the characteristic osteoclast morphology in that they are mitochondria-rich, multinucleated, and, most importantly, develop characteristic ruffled membranes at the matrix attachment site. Moreover, as documented by scanning electron microscopy, these cells pit bone slices in a manner identical to freshly isolated osteoclasts. In addition, isoenzymes of acid phosphatase from generated osteoclasts, separated by 7.5% polyacrylamide gel electrophoresis at pH 4, are identical to those of mature osteoclasts in migration pattern and tartrate resistance, although the precursor cells from which the osteoclasts are generated produce an entirely different isoenzyme, which is tartrate-sensitive and migrates less rapidly at pH 4. The fused cells also exhibit a cAMP response to prostaglandin E2. Therefore, osteoclast-like cells can be derived by in vitro culture of a marrow-derived monocyte cell population.

  3. HAIR CELL-LIKE CELL GENERATION INDUCED BY NATURE CULTURE OF ADULT RAT AUDITORY EPITHELIUM

    Institute of Scientific and Technical Information of China (English)

    Liu Hui; Zhu Hongliang; Li Shengli; Yao Xiaobao; Wang Xiaoxia

    2006-01-01

    Objective To establish adult rat auditory epithelial cell culture and try to find precursor cells of auditory hair cells in vitro. Methods With refinement of culture media and techniques, cochlear sensory epithelial cells of adult rat were cultured. Immunocytochemistry and Bromodeoxyuridine (BrdU)labeling were used to detect properties and mitotic status of cultured cells. Results The cultured auditory epithelial cells showed a large, flat epithelial morphotype and expressed F-actin and cytokeratin, a subset of cells generated from auditory epithelium were labeled by calretinin, a specific marker of early hair cell. Conclusion Adult rat auditory epithelium can be induced to generate hair cell-like cells by nature culture, this phenomenon suggests that progenitor cells may exist in rat cochlea and they may give birth to new hair cells. Whether these progenitor cells are tissue specific stem cells is still need more study.

  4. Generation of iPS Cells from Human Peripheral Blood Mononuclear Cells Using Episomal Vectors.

    Science.gov (United States)

    Su, Ruijun Jeanna; Neises, Amanda; Zhang, Xiao-Bing

    2016-01-01

    Peripheral blood is the easy-to-access, minimally invasive, and the most abundant cell source to use for cell reprogramming. The episomal vector is among the best approaches for generating integration-free induced pluripotent stem (iPS) cells due to its simplicity and affordability. Here we describe the detailed protocol for the efficient generation of integration-free iPS cells from peripheral blood mononuclear cells. With this optimized protocol, one can readily generate hundreds of iPS cell colonies from 1 ml of peripheral blood.

  5. NANOG priming before full reprogramming may generate germ cell tumours

    Directory of Open Access Journals (Sweden)

    I Grad

    2011-11-01

    Full Text Available Reprogramming somatic cells into a pluripotent state brings patient-tailored, ethical controversy-free cellular therapy closer to reality. However, stem cells and cancer cells share many common characteristics; therefore, it is crucial to be able to discriminate between them. We generated two induced pluripotent stem cell (iPSC lines, with NANOG pre-transduction followed by OCT3/4, SOX2, and LIN28 overexpression. One of the cell lines, CHiPS W, showed normal pluripotent stem cell characteristics, while the other, CHiPS A, though expressing pluripotency markers, failed to differentiate and gave rise to germ cell-like tumours in vivo. Comparative genomic hybridisation analysis of the generated iPS lines revealed that they were genetically more stable than human embryonic stem cell counterparts. This analysis proved to be predictive for the differentiation potential of analysed cells. Moreover, the CHiPS A line expressed a lower ratio of p53/p21 when compared to CHiPS W. NANOG pre-induction followed by OCT3/4, SOX2, MYC, and KLF4 induction resulted in the same tumour-inducing phenotype. These results underline the importance of a re-examination of the role of NANOG during reprogramming. Moreover, this reprogramming method may provide insights into primordial cell tumour formation and cancer stem cell transformation.

  6. Mesenchymal Stem Cells and Induced Pluripotent Stem Cells as Therapies for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Juan Xiao

    2015-04-01

    Full Text Available Multiple sclerosis (MS is a chronic, autoimmune, inflammatory demyelinating disorder of the central nervous system that leads to permanent neurological deficits. Current MS treatment regimens are insufficient to treat the irreversible neurological disabilities. Tremendous progress in the experimental and clinical applications of cell-based therapies has recognized stem cells as potential candidates for regenerative therapy for many neurodegenerative disorders including MS. Mesenchymal stem cells (MSC and induced pluripotent stem cell (iPSCs derived precursor cells can modulate the autoimmune response in the central nervous system (CNS and promote endogenous remyelination and repair process in animal models. This review highlights studies involving the immunomodulatory and regenerative effects of mesenchymal stem cells and iPSCs derived cells in animal models, and their translation into immunomodulatory and neuroregenerative treatment strategies for MS.

  7. A BAC-bacterial recombination method to generate physically linked multiple gene reporter DNA constructs

    Directory of Open Access Journals (Sweden)

    Gong Shiaochin

    2009-03-01

    Full Text Available Abstract Background Reporter gene mice are valuable animal models for biological research providing a gene expression readout that can contribute to cellular characterization within the context of a developmental process. With the advancement of bacterial recombination techniques to engineer reporter gene constructs from BAC genomic clones and the generation of optically distinguishable fluorescent protein reporter genes, there is an unprecedented capability to engineer more informative transgenic reporter mouse models relative to what has been traditionally available. Results We demonstrate here our first effort on the development of a three stage bacterial recombination strategy to physically link multiple genes together with their respective fluorescent protein (FP reporters in one DNA fragment. This strategy uses bacterial recombination techniques to: (1 subclone genes of interest into BAC linking vectors, (2 insert desired reporter genes into respective genes and (3 link different gene-reporters together. As proof of concept, we have generated a single DNA fragment containing the genes Trap, Dmp1, and Ibsp driving the expression of ECFP, mCherry, and Topaz FP reporter genes, respectively. Using this DNA construct, we have successfully generated transgenic reporter mice that retain two to three gene readouts. Conclusion The three stage methodology to link multiple genes with their respective fluorescent protein reporter works with reasonable efficiency. Moreover, gene linkage allows for their common chromosomal integration into a single locus. However, the testing of this multi-reporter DNA construct by transgenesis does suggest that the linkage of two different genes together, despite their large size, can still create a positional effect. We believe that gene choice, genomic DNA fragment size and the presence of endogenous insulator elements are critical variables.

  8. Real-Time Terrain Storage Generation from Multiple Sensors towards Mobile Robot Operation Interface

    Directory of Open Access Journals (Sweden)

    Wei Song

    2014-01-01

    Full Text Available A mobile robot mounted with multiple sensors is used to rapidly collect 3D point clouds and video images so as to allow accurate terrain modeling. In this study, we develop a real-time terrain storage generation and representation system including a nonground point database (PDB, ground mesh database (MDB, and texture database (TDB. A voxel-based flag map is proposed for incrementally registering large-scale point clouds in a terrain model in real time. We quantize the 3D point clouds into 3D grids of the flag map as a comparative table in order to remove the redundant points. We integrate the large-scale 3D point clouds into a nonground PDB and a node-based terrain mesh using the CPU. Subsequently, we program a graphics processing unit (GPU to generate the TDB by mapping the triangles in the terrain mesh onto the captured video images. Finally, we produce a nonground voxel map and a ground textured mesh as a terrain reconstruction result. Our proposed methods were tested in an outdoor environment. Our results show that the proposed system was able to rapidly generate terrain storage and provide high resolution terrain representation for mobile mapping services and a graphical user interface between remote operators and mobile robots.

  9. Dendritic Cells and Multiple Sclerosis: Disease, Tolerance and Therapy

    Directory of Open Access Journals (Sweden)

    Mohammad G. Mohammad

    2012-12-01

    Full Text Available Multiple sclerosis (MS is a devastating neurological disease that predominantly affects young adults resulting in severe personal and economic impact. The majority of therapies for this disease were developed in, or are beneficial in experimental autoimmune encephalomyelitis (EAE, the animal model of MS. While known to target adaptive anti-CNS immune responses, they also target, the innate immune arm. This mini-review focuses on the role of dendritic cells (DCs, the professional antigen presenting cells of the innate immune system. The evidence for a role for DCs in the appropriate regulation of anti-CNS autoimmune responses and their role in MS disease susceptibility and possible therapeutic utility are discussed. Additionally, the current controversy regarding the evidence for the presence of functional DCs in the normal CNS is reviewed. Furthermore, the role of CNS DCs and potential routes of their intercourse between the CNS and cervical lymph nodes are considered. Finally, the future role that this nexus between the CNS and the cervical lymph nodes might play in site directed molecular and cellular therapy for MS is outlined.

  10. Dendritic cell, monocyte and T cell activation and response to glatiramer acetate in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Hesse, D; Limborg, S;

    2012-01-01

    Background: Treatment with glatiramer acetate (GA) modestly decreases disease activity in multiple sclerosis (MS). The mechanism of action is incompletely understood and differences in the response to treatment between individuals may exist. Objective: To study the activation of CD4+ T cells...

  11. Generating a non-integrating human induced pluripotent stem cell bank from urine-derived cells.

    Directory of Open Access Journals (Sweden)

    Yanting Xue

    Full Text Available Induced pluripotent stem cell (iPS cell holds great potential for applications in regenerative medicine, drug discovery, and disease modeling. We describe here a practical method to generate human iPS cells from urine-derived cells (UCs under feeder-free, virus-free, serum-free condition and without oncogene c-MYC. We showed that this approach could be applied in a large population with different genetic backgrounds. UCs are easily accessible and exhibit high reprogramming efficiency, offering advantages over other cell types used for the purpose of iPS generation. Using the approach described in this study, we have generated 93 iPS cell lines from 20 donors with diverse genetic backgrounds. The non-viral iPS cell bank with these cell lines provides a valuable resource for iPS cells research, facilitating future applications of human iPS cells.

  12. Single cell functional analysis of multiple myeloma cell populations correlates with diffusion profiles in static microfluidic coculture systems.

    Science.gov (United States)

    Moore, Thomas A; Young, Edmond W K

    2016-07-01

    Microfluidic cell culture systems are becoming increasingly useful for studying biology questions, particularly those involving small cell populations that are cultured within microscale geometries mimicking the complex cellular microenvironment. Depending on the geometry and spatial organization of these cell populations, however, paracrine signaling between cell types can depend critically on spatial concentration profiles of soluble factors generated by diffusive transport. In scenarios where single cell data are acquired to study cell population heterogeneities in functional response, uncertainty associated with concentration profiles can lead to interpretation bias. To address this issue and provide important evidence on how diffusion develops within typical microfluidic cell culture systems, a combination of experimental and computational approaches were applied to measure and predict concentration patterns within microfluidic geometries, and characterize the functional response of culture cells based on single-cell resolution transcription factor activation. Using a model coculture system consisting of multiple myeloma cells (MMCs) and neighboring bone marrow stromal cells (BMSCs), we measured concentrations of three cytokines (IL-6, VEGF, and TNF-α) in conditioned media collected from separate culture compartments using a multiplex ELISA system. A 3D numerical model was developed to predict biomolecular diffusion and resulting concentration profiles within the tested microsystems and compared with experimental diffusion of 20 kDa FITC-Dextran. Finally, diffusion was further characterized by controlling exogenous IL-6 diffusion and the coculture spatial configuration of BMSCs to stimulate STAT3 nuclear translocation in MMCs. Results showed agreement between numerical and experimental results, provided evidence of a shallow concentration gradient across the center well of the microsystem that did not lead to a bias in results, and demonstrated that

  13. MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis.

    Science.gov (United States)

    Severin, Mary E; Lee, Priscilla W; Liu, Yue; Selhorst, Amanda J; Gormley, Matthew G; Pei, Wei; Yang, Yuhong; Guerau-de-Arellano, Mireia; Racke, Michael K; Lovett-Racke, Amy E

    2016-06-01

    Transforming growth factor beta (TGFβ) signalling is critical for regulatory T cell development and function, and regulatory T cell dysregulation is a common observation in autoimmune diseases, including multiple sclerosis. In a comprehensive miRNA profiling study of patients with multiple sclerosis naïve CD4 T cells, 19 differentially expressed miRNAs predicted to target the TGFβ signalling pathway were identified, leading to the hypothesis that miRNAs may be responsible for the regulatory T cell defect observed in patients with multiple sclerosis. Patients with multiple sclerosis had reduced levels of TGFβ signalling components in their naïve CD4 T cells. The differentially expressed miRNAs negatively regulated the TGFβ pathway, resulting in a reduced capacity of naïve CD4 T cells to differentiate into regulatory T cells. Interestingly, the limited number of regulatory T cells, that did develop when these TGFβ-targeting miRNAs were overexpressed, were capable of suppressing effector T cells. As it has previously been demonstrated that compromising TGFβ signalling results in a reduced regulatory T cell repertoire insufficient to control autoimmunity, and patients with multiple sclerosis have a reduced regulatory T cell repertoire, these data indicate that the elevated expression of multiple TGFβ-targeting miRNAs in naïve CD4 T cells of patients with multiple sclerosis impairs TGFβ signalling, and dampens regulatory T cell development, thereby enhancing susceptibility to developing multiple sclerosis.

  14. Thymoquinone causes multiple effects, including cell death, on dividing plant cells.

    Science.gov (United States)

    Hassanien, Sameh E; Ramadan, Ahmed M; Azeiz, Ahmed Z Abdel; Mohammed, Rasha A; Hassan, Sabah M; Shokry, Ahmed M; Atef, Ahmed; Kamal, Khalid B H; Rabah, Samar; Sabir, Jamal S M; Abuzinadah, Osama A; El-Domyati, Fotouh M; Martin, Gregory B; Bahieldin, Ahmed

    2013-01-01

    Thymoquinone (TQ) is a major constituent of Nigella sativa oil with reported anti-oxidative activity and anti-inflammatory activity in animal cells. It also inhibits proliferation and induces programmed cell death (apoptosis) in human skin cancer cells. The present study sought to detect the influence of TQ on dividing cells of three plant systems and on expression of Bcl2-associated athanogene-like (BAG-like) genes that might be involved during the process of cell death. BAG genes are known for the regulation of diverse physiological processes in animals, including apoptosis, tumorigenesis, stress responses, and cell division. Synthetic TQ at 0.1mg/mL greatly reduced wheat seed germination rate, whereas 0.2mg/mL completely inhibited germination. An Evans blue assay revealed moderate cell death in the meristematic zone of Glycine max roots after 1h of TQ treatment (0.2mg/mL), with severe cell death occurring in this zone after 2h of treatment. Light microscopy of TQ-treated (0.2mg/mL) onion hairy root tips for 1h revealed anti-mitotic activity and also cell death-associated changes, including nuclear membrane disruption and nuclear fragmentation. Transmission electron microscopy of TQ-treated cells (0.2mg/mL) for 1h revealed shrinkage of the plasma membrane, leakage of cell lysate, degradation of cell walls, enlargement of vacuoles and condensation of nuclei. Expression of one BAG-like gene, previously associated with cell death, was induced 20 min after TQ treatment in Glycine max root tip cells. Thus, TQ has multiple effects, including cell death, on dividing plant cells and plants may serve as a useful system to further investigate the mechanisms underlying the response of eukaryotic cells to TQ. PMID:24296078

  15. Molecular diagnostics of a single drug-resistant multiple myeloma case using targeted next-generation sequencing

    Directory of Open Access Journals (Sweden)

    Ikeda H

    2015-10-01

    Full Text Available Hiroshi Ikeda,1 Kazuya Ishiguro,1 Tetsuyuki Igarashi,1 Yuka Aoki,1 Toshiaki Hayashi,1 Tadao Ishida,1 Yasushi Sasaki,1,2 Takashi Tokino,2 Yasuhisa Shinomura1 1Department of Gastroenterology, Rheumatology and Clinical Immunology, 2Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan Abstract: A 69-year-old man was diagnosed with IgG λ-type multiple myeloma (MM, Stage II in October 2010. He was treated with one cycle of high-dose dexamethasone. After three cycles of bortezomib, the patient exhibited slow elevations in the free light-chain levels and developed a significant new increase of serum M protein. Bone marrow cytogenetic analysis revealed a complex karyotype characteristic of malignant plasma cells. To better understand the molecular pathogenesis of this patient, we sequenced for mutations in the entire coding regions of 409 cancer-related genes using a semiconductor-based sequencing platform. Sequencing analysis revealed eight nonsynonymous somatic mutations in addition to several copy number variants, including CCND1 and RB1. These alterations may play roles in the pathobiology of this disease. This targeted next-generation sequencing can allow for the prediction of drug resistance and facilitate improvements in the treatment of MM patients. Keywords: multiple myeloma, drug resistance, genome-wide sequencing, semiconductor sequencer, target therapy

  16. Identifying the multiplicity of crystallographically equivalent variants generated by iterative phase transformations in Ti.

    Science.gov (United States)

    Grammatikopoulos, Panagiotis; Pond, Robert Charles

    2016-02-01

    This work describes phase transformations in Ti from a purely crystallographic perspective. Iterative heating and cooling above and below 1155 K induce phase transitions between a low-temperature h.c.p. (hexagonal close packed) (6/m mm) and a high-temperature b.c.c. (body centred cubic) (m3m) structure. The crystallography of the two phases has been found to be related by the Burgers Orientation Relationship (Burgers OR). The transitions are accompanied by changes in texture, as an ever-increasing number of crystallographically equivalent variants occur with every cycle. Identifying their multiplicity is important to relate the textures before and after the transformation, in order to predict the resultant one and refine its microstructure. The four-dimensional Frank space was utilized to describe both h.c.p. and b.c.c. structures within the same orthogonal framework, and thus allow for their easy numerical manipulation through matrix algebra. Crystallographic group decomposition showed that the common symmetry maintained in both groups was that of group 2/m; therefore, the symmetry operations that generated the variants were of groups 3m and 23 for cubic and hexagonal generations, respectively. The number of all potential variants was determined for the first three variant generations, and degeneracy was indeed detected, reducing the number of variants from 72 to 57 and from 432 to 180 for the second and third generations, respectively. Degeneracy was attributed on some special alignments of symmetry operators, as a result of the Burgers OR connecting the relative orientation of the two structures. PMID:26830797

  17. Generation of suppressive blood cells for control of allograft rejection.

    Science.gov (United States)

    Kleist, Christian; Sandra-Petrescu, Flavius; Jiga, Lucian; Dittmar, Laura; Mohr, Elisabeth; Greil, Johann; Mier, Walter; Becker, Luis E; Lang, Peter; Opelz, Gerhard; Terness, Peter

    2015-05-01

    Our previous studies in rats showed that incubation of monocytic dendritic cells (DCs) with the chemotherapeutic drug mitomycin C (MMC) renders the cells immunosuppressive. Donor-derived MMC-DCs injected into the recipient prior to transplantation prolonged heart allograft survival. Although the generation of DCs is labour-intensive and time-consuming, peripheral blood mononuclear cells (PBMCs) can be easily harvested. In the present study, we analyse under which conditions DCs can be replaced by PBMCs and examine their mode of action. When injected into rats, MMC-incubated donor PBMCs (MICs) strongly prolonged heart allograft survival. Removal of monocytes from PBMCs completely abrogated their suppressive effect, indicating that monocytes are the active cell population. Suppression of rejection was donor-specific. The injected MICs migrated into peripheral lymphoid organs and led to an increased number of regulatory T-cells (Tregs) expressing cluster of differentiation (CD) markers CD4 and CD25 and forkhead box protein 3 (FoxP3). Tolerance could be transferred to syngeneic recipients with blood or spleen cells. Depletion of Tregs from tolerogenic cells abrogated their suppressive effect, arguing for mediation of immunosuppression by CD4⁺CD25⁺FoxP3⁺ Tregs. Donor-derived MICs also prolonged kidney allograft survival in pigs. MICs generated from donor monocytes were applied for the first time in humans in a patient suffering from therapy-resistant rejection of a haploidentical stem cell transplant. We describe, in the present paper, a simple method for in vitro generation of suppressor blood cells for potential use in clinical organ transplantation. Although the case report does not allow us to draw any conclusion about their therapeutic effectiveness, it shows that MICs can be easily generated and applied in humans.

  18. Infrared Supercontinuum Generation in Multiple Quantum Well Nanostructures under Electromagnetically Induced Transparency

    CERN Document Server

    Borgohain, Nitu; Konar, S

    2015-01-01

    Mid-infrared spectral broadening is of great scientific and technological interest, which till date is mainly achieved using non-silica glass fibers, primarily made of tellurite, fluoride and chalcogenide glasses. We investigate broadband mid-infrared supercontinuum generation at very low power in semiconductor multiple quantum well (MQW) systems facilitated by electromagnetically induced transparency. 100 femto-seconds pulses of peak power close to a Watt have been launched in the electromagnetically induced transparency window of a 30 period 1.374 {\\mu}m long MQW system. Broadband supercontinuum spectra, attributed to self phase modulation and modulation instability, is achievable at the end of the MQW system. The central part of the spectra is dominated by several dips and the far infra-red part of the spectra is more broadened in comparison to the infra-red portion. Key advantage of the proposed scheme is that the supercontinuum source could be easily integrated with other semiconductor devices.

  19. Simple and inexpensive microfluidic devices for the generation of monodisperse multiple emulsions

    KAUST Repository

    Li, Erqiang

    2013-12-16

    Droplet-based microfluidic devices have become a preferred versatile platform for various fields in physics, chemistry and biology. Polydimethylsiloxane soft lithography, the mainstay for fabricating microfluidic devices, usually requires the usage of expensive apparatus and a complex manufacturing procedure. Here, we report the design and fabrication of simple and inexpensive microfluidic devices based on microscope glass slides and pulled glass capillaries, for generating monodisperse multiple emulsions. The advantages of our method lie in a simple manufacturing procedure, inexpensive processing equipment and flexibility in the surface modification of the designed microfluidic devices. Different types of devices have been designed and tested and the experimental results demonstrated their robustness for preparing monodisperse single, double, triple and multi-component emulsions. © 2014 IOP Publishing Ltd.

  20. Simultaneous Cell-to-Cell Transmission of Human Immunodeficiency Virus to Multiple Targets through Polysynapses▿ †

    Science.gov (United States)

    Rudnicka, Dominika; Feldmann, Jérôme; Porrot, Françoise; Wietgrefe, Steve; Guadagnini, Stéphanie; Prévost, Marie-Christine; Estaquier, Jérôme; Haase, Ashley T.; Sol-Foulon, Nathalie; Schwartz, Olivier

    2009-01-01

    Human immunodeficiency virus type 1 (HIV-1) efficiently propagates through cell-to-cell contacts, which include virological synapses (VS), filopodia, and nanotubes. Here, we quantified and characterized further these diverse modes of contact in lymphocytes. We report that viral transmission mainly occurs across VS and through “polysynapses,” a rosette-like structure formed between one infected cell and multiple adjacent recipients. Polysynapses are characterized by simultaneous HIV clustering and transfer at multiple membrane regions. HIV Gag proteins often adopt a ring-like supramolecular organization at sites of intercellular contacts and colocalize with CD63 tetraspanin and raft components GM1, Thy-1, and CD59. In donor cells engaged in polysynapses, there is no preferential accumulation of Gag proteins at contact sites facing the microtubule organizing center. The LFA-1 adhesion molecule, known to facilitate viral replication, enhances formation of polysynapses. Altogether, our results reveal an underestimated mode of viral transfer through polysynapses. In HIV-infected individuals, these structures, by promoting concomitant infection of multiple targets in the vicinity of infected cells, may facilitate exponential viral growth and escape from immune responses. PMID:19369333

  1. RNA interference mediated inhibition of dengue virus multiplication and entry in HepG2 cells.

    Directory of Open Access Journals (Sweden)

    Mohammed Abdelfatah Alhoot

    Full Text Available BACKGROUND: Dengue virus-host cell interaction initiates when the virus binds to the attachment receptors followed by endocytic internalization of the virus particle. Successful entry into the cell is necessary for infection initiation. Currently, there is no protective vaccine or antiviral treatment for dengue infection. Targeting the viral entry pathway has become an attractive therapeutic strategy to block infection. This study aimed to investigate the effect of silencing the GRP78 and clathrin-mediated endocytosis on dengue virus entry and multiplication into HepG2 cells. METHODOLOGY/PRINCIPAL FINDINGS: HepG2 cells were transfected using specific siRNAs to silence the cellular surface receptor (GRP78 and clathrin-mediated endocytosis pathway. Gene expression analysis showed a marked down-regulation of the targeted genes (87.2%, 90.3%, and 87.8% for GRP78, CLTC, and DNM2 respectively in transfected HepG2 cells when measured by RT-qPCR. Intracellular and extracellular viral RNA loads were quantified by RT-qPCR to investigate the effect of silencing the attachment receptor and clathrin-mediated endocytosis on dengue virus entry. Silenced cells showed a significant reduction of intracellular (92.4% and extracellular viral RNA load (71.4% compared to non-silenced cells. Flow cytometry analysis showed a marked reduction of infected cells (89.7% in silenced HepG2 cells compared to non-silenced cells. Furthermore, the ability to generate infectious virions using the plaque assay was reduced 1.07 log in silenced HepG2 cells. CONCLUSIONS/SIGNIFICANCE: Silencing the attachment receptor and clathrin-mediated endocytosis using siRNA could inhibit dengue virus entry and multiplication into HepG2 cells. This leads to reduction of infected cells as well as the viral load, which might function as a unique and promising therapeutic agent for attenuating dengue infection and prevent the development of dengue fever to the severe life-threatening DHF or DSS

  2. Unequal distribution of plastids during generative cell formation in Impatiens.

    Science.gov (United States)

    van Went, J L

    1984-07-01

    This paper describes the unequal distribution of plastids in the developing microspores of Impatiens walleriana and Impatiens glandulifera which leads to the exclusion of plastids from the generative cell. During the development from young microspore to the onset of mitosis a change in the organization of the cytoplasm and distribution of organelles is gradually established. This includes the formation of vacuoles at the poles of the elongate-shaped microspores, the movement of the nucleus to a position near the microspore wall in the central part of the cell, and the accumulation of the plastids to a position near the wall at the opposite side of the cell. In Impatiens walleriana, the accumulated plastids are separated from each other by ER cisterns, and some mitochondria are also accumulated. In both Impatiens species, the portion of the microspore in which the generative cell will be formed is completely devoid of plastids at the time mitosis starts. PMID:24257638

  3. A methanotroph-based biorefinery: Potential scenarios for generating multiple products from a single fermentation.

    Science.gov (United States)

    Strong, P J; Kalyuzhnaya, M; Silverman, J; Clarke, W P

    2016-09-01

    Methane, a carbon source for methanotrophic bacteria, is the principal component of natural gas and is produced during anaerobic digestion of organic matter (biogas). Methanotrophs are a viable source of single cell protein (feed supplement) and can produce various products, since they accumulate osmolytes (e.g. ectoine, sucrose), phospholipids (potential biofuels) and biopolymers (polyhydroxybutyrate, glycogen), among others. Other cell components, such as surface layers, metal chelating proteins (methanobactin), enzymes (methane monooxygenase) or heterologous proteins hold promise as future products. Here, scenarios are presented where ectoine, polyhydroxybutyrate or protein G are synthesised as the primary product, in conjunction with a variety of ancillary products that could enhance process viability. Single or dual-stage processes and volumetric requirements for bioreactors are discussed, in terms of an annual biomass output of 1000 tonnesyear(-1). Product yields are discussed in relation to methane and oxygen consumption and organic waste generation. PMID:27146469

  4. Peer generation of multiple-choice questions: student engagement and experiences.

    Science.gov (United States)

    Rhind, Susan M; Pettigrew, Graham W

    2012-01-01

    A free online system for generation of multiple-choice questions (PeerWise) was implemented in three courses (course A, B, and C) in two different years (second and third year) of a veterinary degree program. Students were asked to author questions, and answer and rate each other's questions. Student experiences of the system were explored using an online survey. The majority of students in both years either agreed or strongly agreed that both authoring and answering questions was helpful for their studies and wanted to use the system again in future courses. Thematic analysis highlighted students' views that engaging with the resource increased breadth and depth of knowledge and understanding and was very useful for revision purposes. There was a statistically significant difference between students in second and third year regarding whether students felt it was necessary for academic staff to be involved in the review process. Thematic analysis of this aspect identified issues relating to confidence in the ability of the peer group and the need for reassurance in the second-year group. Student engagement with the system was correlated with examination performance. In courses A and B there was a positive correlation between number of questions answered and examination performance, in course C there was no correlation. This study highlights the benefits of peer activity around question generation and proposes that such activities are an efficient and effective means to support student learning.

  5. Random number generation deficits in patients with multiple sclerosis: Characteristics and neural correlates.

    Science.gov (United States)

    Geisseler, Olivia; Pflugshaupt, Tobias; Buchmann, Andreas; Bezzola, Ladina; Reuter, Katja; Schuknecht, Bernhard; Weller, David; Linnebank, Michael; Brugger, Peter

    2016-09-01

    Human subjects typically deviate systematically from randomness when attempting to produce a sequence of random numbers. Despite an increasing number of behavioral and functional neuroimaging studies on random number generation (RNG), its structural correlates have never been investigated. We set out to fill this gap in 44 patients with multiple sclerosis (MS), a disease whose impact on RNG has never been studied. The RNG task required the paced (1 Hz) generation of the numbers from 1 to 6 in a sequence as random as possible. The same task was administered in 39 matched healthy controls. To assess neuroanatomical correlates such as cortical thickness, lesion load and third ventricle width, all subjects underwent high-resolution structural MRI. Compared to controls, MS patients exhibited an enhanced tendency to arrange consecutive numbers in an ascending order ("forward counting"). Furthermore, patients showed a higher susceptibility to rule breaks (producing out-of-category digits like 7) and to skip beats of the metronome. Clinico-anatomical correlation analyses revealed two main findings: First, increased counting in MS patients was associated with higher cortical lesion load. Second, increased number of skipped beats was related to widespread cortical thinning. In conclusion, our test results illustrate a loss of behavioral complexity in the course of MS, while the imaging results suggest an association between this loss and cortical pathology. PMID:27403852

  6. Study on the regulatory approach of KNGR multiple steam generator tube rupture events

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Keun Sun; Kweon, Y. C.; Lee, S. J.; Lee, Y. S.; Cheong, D. Y.; Park, T. J.; Lee, M. G.; Cheon, Y. H. [Sunmoon Univ., Asan (Korea, Republic of); Cheong, J. H. [Baekseok College of Cultural Studies, Cheonan (Korea, Republic of)

    2001-10-15

    The scope and contents performed in this project are as follows : firstly, reviews of the structure and contents of local and foreign regulatory requirements as well as analysis of design features related to safety improvement and containment bypass during multiple steam generator tube failure of advanced reactors of domestic and foreign countries. Secondly, analyses of the state-of-the-art of the development of local and foreign regulatory requirements, research trends, design features and safety goals of advanced reactors, especially for technical issues related to the containment bypass during MSGTR event. Thirdly, analyses of the event of MSGTR for the KNGR using MAS 1.4 which is the best-estimate system code developed by Korea Atomic Energy Research Institute. Errors in input-decks established last year have been corrected during this analysis. Fourthly, assessment of the effects of several parameters on the consequences following a MSGTR event. Tube rupture location, selection of affected steam generator, tube modeling method, discharge coefficient (C{sub D}) are examined. Fifthly, establishment of regulatory direction of technical issues related to the containment bypass during MSGTR event.

  7. Random number generation deficits in patients with multiple sclerosis: Characteristics and neural correlates.

    Science.gov (United States)

    Geisseler, Olivia; Pflugshaupt, Tobias; Buchmann, Andreas; Bezzola, Ladina; Reuter, Katja; Schuknecht, Bernhard; Weller, David; Linnebank, Michael; Brugger, Peter

    2016-09-01

    Human subjects typically deviate systematically from randomness when attempting to produce a sequence of random numbers. Despite an increasing number of behavioral and functional neuroimaging studies on random number generation (RNG), its structural correlates have never been investigated. We set out to fill this gap in 44 patients with multiple sclerosis (MS), a disease whose impact on RNG has never been studied. The RNG task required the paced (1 Hz) generation of the numbers from 1 to 6 in a sequence as random as possible. The same task was administered in 39 matched healthy controls. To assess neuroanatomical correlates such as cortical thickness, lesion load and third ventricle width, all subjects underwent high-resolution structural MRI. Compared to controls, MS patients exhibited an enhanced tendency to arrange consecutive numbers in an ascending order ("forward counting"). Furthermore, patients showed a higher susceptibility to rule breaks (producing out-of-category digits like 7) and to skip beats of the metronome. Clinico-anatomical correlation analyses revealed two main findings: First, increased counting in MS patients was associated with higher cortical lesion load. Second, increased number of skipped beats was related to widespread cortical thinning. In conclusion, our test results illustrate a loss of behavioral complexity in the course of MS, while the imaging results suggest an association between this loss and cortical pathology.

  8. Nanoprobe arrays for multiple single cell insertion using heterogeneous nanosphere lithography (HNSL)

    Science.gov (United States)

    Seo, Yoon Ho; Kim, Lo Hyun; Kim, Young-Beom; Ryu, Wonhyoung

    2013-08-01

    Nanoprobe arrays for multiple single cell insertion were developed using heterogeneous nanosphere lithography. Using two heterogeneous nanoparticles as sacrificial and masking particles, high aspect ratio Si nanoprobes were fabricated in an array with spacing between the nanoprobes ranging from a few to tens of micrometers. For registered single cell analysis, multiple and precise insertion of nanoprobes into multiple single cells in a parallel fashion was demonstrated using micropipette suction and micromanipulators.

  9. Multiple account benefit-cost evaluation of the Burrard Thermal Generating Plant

    International Nuclear Information System (INIS)

    The government of British Columbia commissioned a multiple account benefit-cost analysis of the Burrard Thermal Generating Plant to ensure that the power production is in the economic and environmental interest of the province. The power plant consists of 6 natural gas-fired generating units with a combined capacity of 950 MW. It has been updated in recent years to reduce local emissions and to increase plant availability and reliability. Burrard has contributed in a major way to BC Hydro's net revenues, but there have been concerns that BC Hydro's purchases of natural gas for the power plant have contributed to the sharp increases in natural gas prices in 2001. There have also been concerns about air emissions from Burrard, including greenhouse gases and nitrous oxides. Historically, the plant has been beneficial, but this report will determine if it is in the provincial interest to continue operation of Burrard or to turn to alternative scenarios. The alternatives include constraining Burrard's output, or shutting it down and replacing it with other resources and repowering the plant with more efficient combined cycle gas turbine technology. In the constrained scenario, Burrard output and net exports are reduced. In the repowering scenario, investment and output at Burrard is increased. The financial consequences of these impacts are measured by their effect on the net system costs of meeting BC Hydro's load. The report demonstrated that it would not be in the overall interest of the province to constrain the operation of Burrard or shut it down. It was recommended that BC Hydro should review in detail the repowering option for Burrard, and that the government should consider imposing an emission charge reflecting the estimated damage costs associated with local pollutants generated at Burrard. The revenues would be used to fund offset measures in the Lower Fraser Valley airshed. 29 refs., 29 tabs., 3 appendices

  10. Multiple account benefit-cost evaluation of the Burrard Thermal Generating Plant

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-04-01

    The government of British Columbia commissioned a multiple account benefit-cost analysis of the Burrard Thermal Generating Plant to ensure that the power production is in the economic and environmental interest of the province. The power plant consists of 6 natural gas-fired generating units with a combined capacity of 950 MW. It has been updated in recent years to reduce local emissions and to increase plant availability and reliability. Burrard has contributed in a major way to BC Hydro's net revenues, but there have been concerns that BC Hydro's purchases of natural gas for the power plant have contributed to the sharp increases in natural gas prices in 2001. There have also been concerns about air emissions from Burrard, including greenhouse gases and nitrous oxides. Historically, the plant has been beneficial, but this report will determine if it is in the provincial interest to continue operation of Burrard or to turn to alternative scenarios. The alternatives include constraining Burrard's output, or shutting it down and replacing it with other resources and repowering the plant with more efficient combined cycle gas turbine technology. In the constrained scenario, Burrard output and net exports are reduced. In the repowering scenario, investment and output at Burrard is increased. The financial consequences of these impacts are measured by their effect on the net system costs of meeting BC Hydro's load. The report demonstrated that it would not be in the overall interest of the province to constrain the operation of Burrard or shut it down. It was recommended that BC Hydro should review in detail the repowering option for Burrard, and that the government should consider imposing an emission charge reflecting the estimated damage costs associated with local pollutants generated at Burrard. The revenues would be used to fund offset measures in the Lower Fraser Valley airshed. 29 refs., 29 tabs., 3 appendices.

  11. Everolimus for Compassionate Use in Multiple Basal Cell Carcinomas

    Directory of Open Access Journals (Sweden)

    Laura Eibenschutz

    2013-01-01

    Full Text Available Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR and has been shown to have antineoplastic activity in addition to its use as an immunosuppressive agent for the prevention of organ transplant rejection. We report the use of everolimus for the compassionate treatment of four elderly, nontransplant patients presenting with multiple basal cell carcinomas (BCC. All patients had a long history of BCC, had refused surgery as a current treatment option, and did not respond to alternative treatments (including topical 5-fluorouracil and imiquimod. Patients were treated with oral everolimus (1.5–3.0 mg daily for 12 months or longer: a complete and sustained response was seen in one case, and partial responses were seen in two other cases. Everolimus was well tolerated in these elderly patients. These promising preliminary data suggest that further dose-finding, controlled clinical studies are warranted to evaluate the antineoplastic effects of everolimus in patients affected by BCC who cannot or will not undergo surgery.

  12. Generation of bovine transgenics using somatic cell nuclear transfer

    Directory of Open Access Journals (Sweden)

    Stice Steven L

    2003-11-01

    Full Text Available Abstract The ability to produce transgenic animals through the introduction of exogenous DNA has existed for many years. However, past methods available to generate transgenic animals, such as pronuclear microinjection or the use of embryonic stem cells, have either been inefficient or not available in all animals, bovine included. More recently somatic cell nuclear transfer has provided a method to create transgenic animals that overcomes many deficiencies present in other methods. This review summarizes the benefits of using somatic cell nuclear transfer to create bovine transgenics as well as the possible opportunities this method creates for the future.

  13. CIF2Cell: Generating geometries for electronic structure programs

    Science.gov (United States)

    Björkman, Torbjörn

    2011-05-01

    The CIF2Cell program generates the geometrical setup for a number of electronic structure programs based on the crystallographic information in a Crystallographic Information Framework (CIF) file. The program will retrieve the space group number, Wyckoff positions and crystallographic parameters, make a sensible choice for Bravais lattice vectors (primitive or principal cell) and generate all atomic positions. Supercells can be generated and alloys are handled gracefully. The code currently has output interfaces to the electronic structure programs ABINIT, CASTEP, CPMD, Crystal, Elk, Exciting, EMTO, Fleur, RSPt, Siesta and VASP. Program summaryProgram title: CIF2Cell Catalogue identifier: AEIM_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEIM_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU GPL version 3 No. of lines in distributed program, including test data, etc.: 12 691 No. of bytes in distributed program, including test data, etc.: 74 933 Distribution format: tar.gz Programming language: Python (versions 2.4-2.7) Computer: Any computer that can run Python (versions 2.4-2.7) Operating system: Any operating system that can run Python (versions 2.4-2.7) Classification: 7.3, 7.8, 8 External routines: PyCIFRW [1] Nature of problem: Generate the geometrical setup of a crystallographic cell for a variety of electronic structure programs from data contained in a CIF file. Solution method: The CIF file is parsed using routines contained in the library PyCIFRW [1], and crystallographic as well as bibliographic information is extracted. The program then generates the principal cell from symmetry information, crystal parameters, space group number and Wyckoff sites. Reduction to a primitive cell is then performed, and the resulting cell is output to suitably named files along with documentation of the information source generated from any bibliographic information contained in the CIF

  14. Antitumoral Effect of Hibiscus sabdariffa on Human Squamous Cell Carcinoma and Multiple Myeloma Cells.

    Science.gov (United States)

    Malacrida, Alessio; Maggioni, Daniele; Cassetti, Arianna; Nicolini, Gabriella; Cavaletti, Guido; Miloso, Mariarosaria

    2016-10-01

    Cancer is a leading cause of death worldwide. Despite therapeutic improvements, some cancers are still untreatable. Recently there has been an increasing interest in the use of natural substances for cancer prevention and treatment. Hibiscus sabdariffa (HS) is a plant, belonging to Malvaceae family, widespread in South Asia and Central Africa. HS extract (HSE) used in folk medicine, gained researchers' interest thanks to its antioxidant, anti-inflammatory, and chemopreventive properties. In the present study, we initially assessed HSE effect on a panel of human tumor cell lines. Then we focused our study on the following that are most sensitive to HSE action cell lines: Multiple Myeloma (MM) cells (RPMI 8226) and Oral Squamous Cell Carcinoma (OSCC) cells (SCC-25). In both RPMI 8226 and SCC-25 cells, HSE impaired cell growth, exerted a reversible cytostatic effect, and reduced cell motility and invasiveness. We evaluated the involvement of MAPKs ERK1/2 and p38 in HSE effects by using specific inhibitors, U0126 and SB203580, respectively. For both SCC-25 and RPMI 8226, HSE cytostatic effect depends on p38 activation, whereas ERK1/2 modulation is crucial for cell motility and invasiveness. Our results suggest that HSE may be a potential therapeutic agent against MM and OSCC. PMID:27618152

  15. Antitumoral Effect of Hibiscus sabdariffa on Human Squamous Cell Carcinoma and Multiple Myeloma Cells.

    Science.gov (United States)

    Malacrida, Alessio; Maggioni, Daniele; Cassetti, Arianna; Nicolini, Gabriella; Cavaletti, Guido; Miloso, Mariarosaria

    2016-10-01

    Cancer is a leading cause of death worldwide. Despite therapeutic improvements, some cancers are still untreatable. Recently there has been an increasing interest in the use of natural substances for cancer prevention and treatment. Hibiscus sabdariffa (HS) is a plant, belonging to Malvaceae family, widespread in South Asia and Central Africa. HS extract (HSE) used in folk medicine, gained researchers' interest thanks to its antioxidant, anti-inflammatory, and chemopreventive properties. In the present study, we initially assessed HSE effect on a panel of human tumor cell lines. Then we focused our study on the following that are most sensitive to HSE action cell lines: Multiple Myeloma (MM) cells (RPMI 8226) and Oral Squamous Cell Carcinoma (OSCC) cells (SCC-25). In both RPMI 8226 and SCC-25 cells, HSE impaired cell growth, exerted a reversible cytostatic effect, and reduced cell motility and invasiveness. We evaluated the involvement of MAPKs ERK1/2 and p38 in HSE effects by using specific inhibitors, U0126 and SB203580, respectively. For both SCC-25 and RPMI 8226, HSE cytostatic effect depends on p38 activation, whereas ERK1/2 modulation is crucial for cell motility and invasiveness. Our results suggest that HSE may be a potential therapeutic agent against MM and OSCC.

  16. Multi-gene gateway clone design for expression of multiple heterologous genes in living cells: modular construction of multiple cDNA expression elements using recombinant cloning.

    Science.gov (United States)

    Sone, Takefumi; Yahata, Kazuhide; Sasaki, Yukari; Hotta, Junko; Kishine, Hiroe; Chesnut, Jonathan D; Imamoto, Fumio

    2008-09-10

    Much attention has been focused on manipulating multiple genes in living cells for analyzing protein function. In order to perform high-throughput generation of multi-gene expression clones, gateway cloning technology (which represents a high-throughput DNA transfer from vector to vector) can be anticipated. In the conventional strategy for gateway cloning, the construction of two or more expression elements into tandem elements on a single plasmid requires the recombination of multiple entry clones with a destination vector in a single reaction mixture. Use of increasing numbers of entry clones in a single reaction is inefficient due to the difficulty in successfully recognizing multiple pairs of matched att signals simultaneously. To address this problem, a "Modular Destination" vector has been devised and constructed, whereby cDNA inserts are sequentially introduced, resulting in a tandem structure with multiple inserts. Whereas the standard destination vector contains only Cm(R) and ccdB genes flanked by two attR signals, this destination vector contains, in addition, one or two cDNA expression elements. Here, we show the rapid construction of expression vectors containing three or four tandemly arrayed cDNA expression elements and their expression in mammalian cells.

  17. Modelling Action Potential Generation and Propagation in Fibroblastic Cells

    Science.gov (United States)

    Torres, J. J.; Cornelisse, L. N.; Harks, E. G. A.; Theuvenet, A. P. R.; Ypey, D. L.

    2003-04-01

    Using a standard Hodgkin-Huxley (HH) formalism, we present a mathematical model for action potential (AP) generation and intercellular AP propagation in quiescent (serum-deprived) normal rat kidney (NRK) fibroblasts [1], based on the recent experimental identification of the ion channels involved [2]. The principal ion channels described are those of an inwardly rectifying K+ conductance (GKIR), an L-type calcium conductance (GCaL), an intracellular calcium activated Cl- conductance (GCl(Ca)), a residual leak conductance Gleak, and gap junctional channels between the cells (Ggj). The role of each one of these components in the particular shape of the AP wave-form has been analyzed and compared with experimental observations. In addition, we have studied the role of subcellular processes like intracellular calcium dynamics and calcium buffering in AP generation. AP propagation between cells was reconstructed in a hexagonal model of cells coupled by Ggj with physiological conductance values. The model revealed an excitability mechanism of quiescent NRK cells with a particular role of intracellular calcium dynamics. It allows further explorations of the mechanism of signal generation and transmission in NRK cell cultures and its dependence on growth conditions.

  18. Large-scale generation of cell-derived nanovesicles

    Science.gov (United States)

    Jo, W.; Kim, J.; Yoon, J.; Jeong, D.; Cho, S.; Jeong, H.; Yoon, Y. J.; Kim, S. C.; Gho, Y. S.; Park, J.

    2014-09-01

    Exosomes are enclosed compartments that are released from cells and that can transport biological contents for the purpose of intercellular communications. Research into exosomes is hindered by their rarity. In this article, we introduce a device that uses centrifugal force and a filter with micro-sized pores to generate a large quantity of cell-derived nanovesicles. The device has a simple polycarbonate structure to hold the filter, and operates in a common centrifuge. Nanovesicles are similar in size and membrane structure to exosomes. Nanovesicles contain intracellular RNAs ranging from microRNA to mRNA, intracellular proteins, and plasma membrane proteins. The quantity of nanovesicles produced using the device is 250 times the quantity of naturally secreted exosomes. Also, the quantity of intracellular contents in nanovesicles is twice that in exosomes. Nanovesicles generated from murine embryonic stem cells can transfer RNAs to target cells. Therefore, this novel device and the nanovesicles that it generates are expected to be used in exosome-related research, and can be applied in various applications such as drug delivery and cell-based therapy.

  19. Development of a Recombination System for the Generation of Occlusion Positive Genetically Modified Anticarsia Gemmatalis Multiple Nucleopolyhedrovirus

    Directory of Open Access Journals (Sweden)

    Santiago Haase

    2015-03-01

    Full Text Available Anticarsia gemmatalis is an important pest in legume crops in South America and it has been successfully controlled using Anticarsia gemmatalis Multiple Nucleopolyhedrovirus (AgMNPV in subtropical climate zones. Nevertheless, in temperate climates its speed of kill is too slow. Taking this into account, genetic modification of AgMNPV could lead to improvements of its biopesticidal properties. Here we report the generation of a two-component system that allows the production of recombinant AgMNPV. This system is based on a parental AgMNPV in which the polyhedrin gene (polh was replaced by a bacterial β-galactosidase (lacZ gene flanked by two target sites for the homing endonuclease I-PpoI. Co-transfection of insect cells with linearized (I-PpoI-digested parental genome and a transfer vector allowed the restitution of polh and the expression of a heterologous gene upon homologous recombination, with a low background of non-recombinant AgMNPV. The system was validated by constructing a recombinant occlusion-positive (polh+ AgMNPV expressing the green fluorescent protein gene (gfp. This recombinant virus infected larvae normally per os and led to the expression of GFP in cell culture as well as in A. gemmatalis larvae. These results demonstrate that the system is an efficient method for the generation of recombinant AgMNPV expressing heterologous genes, which can be used for manifold purposes, including biotechnological and pharmaceutical applications and the production of orally infectious recombinants with improved biopesticidal properties.

  20. Cross-Generational Reproductive Fitness Enforced by Microchimeric Maternal Cells.

    Science.gov (United States)

    Kinder, Jeremy M; Jiang, Tony T; Ertelt, James M; Xin, Lijun; Strong, Beverly S; Shaaban, Aimen F; Way, Sing Sing

    2015-07-30

    Exposure to maternal tissue during in utero development imprints tolerance to immunologically foreign non-inherited maternal antigens (NIMA) that persists into adulthood. The biological advantage of this tolerance, conserved across mammalian species, remains unclear. Here, we show maternal cells that establish microchimerism in female offspring during development promote systemic accumulation of immune suppressive regulatory T cells (Tregs) with NIMA specificity. NIMA-specific Tregs expand during pregnancies sired by males expressing alloantigens with overlapping NIMA specificity, thereby averting fetal wastage triggered by prenatal infection and non-infectious disruptions of fetal tolerance. Therefore, exposure to NIMA selectively enhances reproductive success in second-generation females carrying embryos with overlapping paternally inherited antigens. These findings demonstrate that genetic fitness, canonically thought to be restricted to Mendelian inheritance, is enhanced in female placental mammals through vertically transferred maternal cells that promote conservation of NIMA and enforce cross-generational reproductive benefits. PMID:26213383

  1. A method for multiple sequential analyses of macrophage functions using a small single cell sample

    Directory of Open Access Journals (Sweden)

    F.R.F. Nascimento

    2003-09-01

    Full Text Available Microbial pathogens such as bacillus Calmette-Guérin (BCG induce the activation of macrophages. Activated macrophages can be characterized by the increased production of reactive oxygen and nitrogen metabolites, generated via NADPH oxidase and inducible nitric oxide synthase, respectively, and by the increased expression of major histocompatibility complex class II molecules (MHC II. Multiple microassays have been developed to measure these parameters. Usually each assay requires 2-5 x 10(5 cells per well. In some experimental conditions the number of cells is the limiting factor for the phenotypic characterization of macrophages. Here we describe a method whereby this limitation can be circumvented. Using a single 96-well microassay and a very small number of peritoneal cells obtained from C3H/HePas mice, containing as little as <=2 x 10(5 macrophages per well, we determined sequentially the oxidative burst (H2O2, nitric oxide production and MHC II (IAk expression of BCG-activated macrophages. More specifically, with 100 µl of cell suspension it was possible to quantify H2O2 release and nitric oxide production after 1 and 48 h, respectively, and IAk expression after 48 h of cell culture. In addition, this microassay is easy to perform, highly reproducible and more economical.

  2. The new generation of vehicles: market opportunities for fuel cells

    Science.gov (United States)

    Chalk, Steven G.; Patil, Pandit G.; Venkateswaran, S. R.

    The Partnership for a New Generation of Vehicles (PNGV), a historic US Government-auto industry partnership initiated in 1993, is pursuing three specific, interrelated goals, including the development of the next generation of vehicles capable of achieving up to three times the fuel efficiency of today's comparable vehicles. Fuel cells have been identified as one of three primary propulsion system candidates to meet this triple fuel efficiency goal, since they can dramatically increase automotive propulsion efficiency combined with very low to zero emissions. The US Government is working closely with industry and research institutions in pursuing a strategy of aggressive research and development (R&D) to accelerate the commercialization of fuel cell vehicles. The US Department of Energy has a major role in this fuel cell technology development effort. R&D activities are focused on overcoming the major technical, economic, and infrastructure-related hurdles. The high efficiency, very low emissions, and other favorable characteristics of fuel cells (such as fuel flexibility, low noise, and vibration) create significant market opportunities for fuel cells over the entire spectrum of transportation applications. While the focus of near-term markets for fuel cell vehicles will be urban areas having severe air-quality problems, long-term market prospects are encouraging since fuel cell vehicles can compete on an even ground with conventional vehicles in all key aspects, including vehicle range and refueling. This paper will discuss near- and long-term market opportunities for fuel cells in transportation and provide an update on driving regulatory developments in the USA at the federal and state level. The paper also provides an introduction to the PNGV (focusing on the role and prospects for fuel cells) and discusses the status of fuel cell vehicle development projects.

  3. The Aryl Hydrocarbon Receptor Antagonist StemRegenin1 Improves In Vitro Generation of Highly Functional Natural Killer Cells from CD34(+) Hematopoietic Stem and Progenitor Cells.

    Science.gov (United States)

    Roeven, Mieke W H; Thordardottir, Soley; Kohela, Arwa; Maas, Frans; Preijers, Frank; Jansen, Joop H; Blijlevens, Nicole M; Cany, Jeannette; Schaap, Nicolaas; Dolstra, Harry

    2015-12-15

    Early natural killer (NK)-cell repopulation after allogeneic stem cell transplantation (allo-SCT) has been associated with reduced relapse rates without an increased risk of graft-versus-host disease, indicating that donor NK cells have specific antileukemic activity. Therefore, adoptive transfer of donor NK cells is an attractive strategy to reduce relapse rates after allo-SCT. Since NK cells of donor origin will not be rejected, multiple NK-cell infusions could be administered in this setting. However, isolation of high numbers of functional NK cells from transplant donors is challenging. Hence, we developed a cytokine-based ex vivo culture protocol to generate high numbers of functional NK cells from granulocyte colony-stimulating factor (G-CSF)-mobilized CD34(+) hematopoietic stem and progenitor cells (HSPCs). In this study, we demonstrate that addition of aryl hydrocarbon receptor antagonist StemRegenin1 (SR1) to our culture protocol potently enhances expansion of CD34(+) HSPCs and induces expression of NK-cell-associated transcription factors promoting NK-cell differentiation. As a result, high numbers of NK cells with an active phenotype can be generated using this culture protocol. These SR1-generated NK cells exert efficient cytolytic activity and interferon-γ production toward acute myeloid leukemia and multiple myeloma cells. Importantly, we observed that NK-cell proliferation and function are not inhibited by cyclosporin A, an immunosuppressive drug often used after allo-SCT. These findings demonstrate that SR1 can be exploited to generate high numbers of functional NK cells from G-CSF-mobilized CD34(+) HSPCs, providing great promise for effective NK-cell-based immunotherapy after allo-SCT.

  4. Generation and characterization of human insulin-releasing cell lines

    Directory of Open Access Journals (Sweden)

    Joffé Elisa

    2009-06-01

    Full Text Available Abstract Background The in vitro culture of insulinomas provides an attractive tool to study cell proliferation and insulin synthesis and secretion. However, only a few human beta cell lines have been described, with long-term passage resulting in loss of insulin secretion. Therefore, we set out to establish and characterize human insulin-releasing cell lines. Results We generated ex-vivo primary cultures from two independent human insulinomas and from a human nesidioblastosis, all of which were cultured up to passage number 20. All cell lines secreted human insulin and C-peptide. These cell lines expressed neuroendocrine and islets markers, confirming the expression profile found in the biopsies. Although all beta cell lineages survived an anchorage independent culture, none of them were able to invade an extracellular matrix substrate. Conclusion We have established three human insulin-releasing cell lines which maintain antigenic characteristics and insulin secretion profiles of the original tumors. These cell lines represent valuable tools for the study of molecular events underlying beta cell function and dysfunction.

  5. Generation and characterization of human insulin-releasing cell lines

    Science.gov (United States)

    Labriola, Leticia; Peters, Maria G; Krogh, Karin; Stigliano, Iván; Terra, Letícia F; Buchanan, Cecilia; Machado, Marcel CC; Joffé, Elisa Bal de Kier; Puricelli, Lydia; Sogayar, Mari C

    2009-01-01

    Background The in vitro culture of insulinomas provides an attractive tool to study cell proliferation and insulin synthesis and secretion. However, only a few human beta cell lines have been described, with long-term passage resulting in loss of insulin secretion. Therefore, we set out to establish and characterize human insulin-releasing cell lines. Results We generated ex-vivo primary cultures from two independent human insulinomas and from a human nesidioblastosis, all of which were cultured up to passage number 20. All cell lines secreted human insulin and C-peptide. These cell lines expressed neuroendocrine and islets markers, confirming the expression profile found in the biopsies. Although all beta cell lineages survived an anchorage independent culture, none of them were able to invade an extracellular matrix substrate. Conclusion We have established three human insulin-releasing cell lines which maintain antigenic characteristics and insulin secretion profiles of the original tumors. These cell lines represent valuable tools for the study of molecular events underlying beta cell function and dysfunction. PMID:19545371

  6. Generation of stomach tissue from mouse embryonic stem cells.

    Science.gov (United States)

    Noguchi, Taka-aki K; Ninomiya, Naoto; Sekine, Mari; Komazaki, Shinji; Wang, Pi-Chao; Asashima, Makoto; Kurisaki, Akira

    2015-08-01

    Successful pluripotent stem cell differentiation methods have been developed for several endoderm-derived cells, including hepatocytes, β-cells and intestinal cells. However, stomach lineage commitment from pluripotent stem cells has remained a challenge, and only antrum specification has been demonstrated. We established a method for stomach differentiation from embryonic stem cells by inducing mesenchymal Barx1, an essential gene for in vivo stomach specification from gut endoderm. Barx1-inducing culture conditions generated stomach primordium-like spheroids, which differentiated into mature stomach tissue cells in both the corpus and antrum by three-dimensional culture. This embryonic stem cell-derived stomach tissue (e-ST) shared a similar gene expression profile with adult stomach, and secreted pepsinogen as well as gastric acid. Furthermore, TGFA overexpression in e-ST caused hypertrophic mucus and gastric anacidity, which mimicked Ménétrier disease in vitro. Thus, in vitro stomach tissue derived from pluripotent stem cells mimics in vivo development and can be used for stomach disease models.

  7. SU-E-T-331: To Evaluate Planning Quality of SBRT with Multiple Lung Metastases Generated with Pinnacle and Tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y [Monmouth Medical Center, Tinton Falls, NJ (United States); Zhang, Y [Cancer Hospital Chinese Academy of Medical Sciences, Chaoyang District, Beijing (China); Zhang, Y [Emory University, Atlanta, GA (United States); Doxsee, K; Yang, C [Monmouth Medical Center, Long Branch, NJ (United States)

    2014-06-01

    Purpose: To evaluate planning quality of SBRT with multiple lung metastases generated with Pinnacle and Tomotherapy Methods: Nine randomly selected patients diagnosed with non small-cell lung cancer with multiple lesions were planned with Pinnacle (version 9.2) and Tomotherapy (version 4.2). Coplanar and non-coplanar plans were generated on Pinnacle. A total dose of 60 Gy was prescribed to 95% of PTV in 3 fractions. Single isocenter was used. Nine static beams were used for Pinnacle plans. Planning outcomes such as minimum and mean dose, V{sub 9} {sub 5}, D{sub 9} {sub 5} (95% of target volume receives prescription dose), D{sub 5}, and D{sub 1} to PTV, maximum dose to heart, esophagus, cord, trachea, brachial plexus, rib, chest wall, and liver, mean dose to liver, total lung, right and left lung, volume of chest wall receives 30 Gy, volume of lungs receives 5 Gy and 20Gy, conformity index (CI = PIV / PTV) and heterogeneity index (HI = D{sub 5} / D{sub 9} {sub 5}) were reported for evaluation. Results: The mean volume of PTV was 37.77 ± 23.4 cm3. D{sub 9} {sub 5} of PTV with Tomo, coplanar, non-coplanar was 60.2 ± 0.3 Gy, 58.6 ± 1.2 Gy, and 59.1 ± 0.7 Gy, respectively. Mean dose to PTV was lower for Tomo (p < 0.0001), so were D{sub 5} (p < 0.0001) and D{sub 1} (p = 0.001). CI was better with Tomo (p < 0.0001), so was HI (p < 0.0001). Maximum dose to other critical organs were also lower exclusively with Tomo plans. Treatment time was recorded only for Tomo plans (73.0 ± 20.6 min). Conclusion: With 51 beam angles, Tomo plans could generally achieve better tumor coverage while sparing more critical structures for multiple lung lesions study. Non-coplanar also has better tumor coverage with lower dose to critical organs such as lungs, liver, chest wall and cord compare to coplanar plans.

  8. Apoptosis of multiple myeloid cells induced by polysaccharides extracts from Hedyotis diffusa and its mechanism

    Institute of Scientific and Technical Information of China (English)

    林圣云

    2013-01-01

    Objective To explore the proliferation inhibition and apoptosis effects of polysaccharides extracts from Hedyotis diffusa(PEHD)on multiple myeloma(MM) cell line RPMI 8226 cells in vitro,so as to provide experimental

  9. The essential role of t cells in multiple sclerosis: A reappraisal

    Directory of Open Access Journals (Sweden)

    Cris S Constantinescu

    2014-04-01

    Full Text Available Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system in which destruction of myelin and nerve axons has been shown to be mediated by immune mechanisms. Although the focus of research has been traditionally on T cells as key mediators of the immunopathology, more recent efforts at understanding this complex disorder have been directed increasingly at other cellular and humoral elements of the immune response. This review is a reappraisal of the crucial role of T cells, in particular the CD4+ helper T-cell subset, in multiple sclerosis. Recent evidence is discussed underlining the predominant contribution of T-cell-associated genes to the genome-wide association study results of multiple sclerosis susceptibility, the loss of T-cell quiescence in the conversion from clinically isolated syndrome to clinically definite multiple sclerosis, and the fact that T cells represent the main target of effective immunomodulatory and immunosuppressive treatments in multiple sclerosis.

  10. Properties of resistant cells generated from lung cancer cell lines treated with EGFR inhibitors

    International Nuclear Information System (INIS)

    Epidermal growth factor receptor (EGFR) signaling plays an important role in non-small cell lung cancer (NSCLC) and therapeutics targeted against EGFR have been effective in treating a subset of patients bearing somatic EFGR mutations. However, the cancer eventually progresses during treatment with EGFR inhibitors, even in the patients who respond to these drugs initially. Recent studies have identified that the acquisition of resistance in approximately 50% of cases is due to generation of a secondary mutation (T790M) in the EGFR kinase domain. In about 20% of the cases, resistance is associated with the amplification of MET kinase. In the remaining 30-40% of the cases, the mechanism underpinning the therapeutic resistance is unknown. An erlotinib resistant subline (H1650-ER1) was generated upon continuous exposure of NSCLC cell line NCI-H1650 to erlotinib. Cancer stem cell like traits including expression of stem cell markers, enhanced ability to self-renew and differentiate, and increased tumorigenicity in vitro were assessed in erlotinib resistant H1650-ER1 cells. The erlotinib resistant subline contained a population of cells with properties similar to cancer stem cells. These cells were found to be less sensitive towards erlotinib treatment as measured by cell proliferation and generation of tumor spheres in the presence of erlotinib. Our findings suggest that in cases of NSCLC accompanied by mutant EGFR, treatment targeting inhibition of EGFR kinase activity in differentiated cancer cells may generate a population of cancer cells with stem cell properties

  11. Generation of Transplantable Beta Cells for Patient-Specific Cell Therapy

    Directory of Open Access Journals (Sweden)

    Xiaojie Wang

    2012-01-01

    Full Text Available Islet cell transplantation offers a potential cure for type 1 diabetes, but it is challenged by insufficient donor tissue and side effects of current immunosuppressive drugs. Therefore, alternative sources of insulin-producing cells and isletfriendly immunosuppression are required to increase the efficiency and safety of this procedure. Beta cells can be transdifferentiated from precursors or another heterologous (non-beta-cell source. Recent advances in beta cell regeneration from somatic cells such as fibroblasts could circumvent the usage of immunosuppressive drugs. Therefore, generation of patient-specific beta cells provides the potential of an evolutionary treatment for patients with diabetes.

  12. Impacts of Variability and Uncertainty in Solar Photovoltaic Generation at Multiple Timescales

    Energy Technology Data Exchange (ETDEWEB)

    Ela, E.; Diakov, V.; Ibanez, E.; Heaney, M.

    2013-05-01

    The characteristics of variability and uncertainty of PV solar power have been studied extensively. These characteristics can create challenges for system operators who must ensure a balance between generation and demand while obeying power system constraints at the lowest possible cost. A number of studies have looked at the impact of wind power plants, and some recent studies have also included solar PV. The simulations that are used in these studies, however, are typically fixed to one time resolution. This makes it difficult to analyze the variability across several timescales. In this study, we use a simulation tool that has the ability to evaluate both the economic and reliability impacts of PV variability and uncertainty at multiple timescales. This information should help system operators better prepare for increases of PV on their systems and develop improved mitigation strategies to better integrate PV with enhanced reliability. Another goal of this study is to understand how different mitigation strategies and methods can improve the integration of solar power more reliably and efficiently.

  13. Dynamics of fragmentation and multiple vacancy generation in irradiated single-walled carbon nanotubes

    International Nuclear Information System (INIS)

    The results from mass spectrometry of clusters sputtered from Cs+ irradiated single-walled carbon nanotubes (SWCNTs) as a function of energy and dose identify the nature of the resulting damage in the form of multiple vacancy generation. For pristine SWCNTs at all Cs+ energies, C2 is the most dominant species, followed by C3, C4 and C1. The experiments were performed in three stages: in the first stage, Cs+ energy E(Cs+) was varied. During the second stage, the nanotubes were irradiated continuously at E(Cs+) = 5 keV for 1,800 s. Afterwards, the entire sequence of irradiation energies was repeated to differentiate between the fragmentation patterns of the pristine and of heavily irradiated SWCNTs. The sputtering and normalized yields identify the quantitative and relative extent of the ion-induced damage by creating double, triple and quadruple vacancies; the single vacancies are least favored. Sputtering from the heavily irradiated SWCNTs occurs not only from the damaged and fragmented nanotubes, but also from the inter-nanotube structures that are grown due to the accumulation of the sputtered clusters. Similar irradiation experiments were performed with the multi-walled carbon nanotubes; the results confirmed the dominant C2 followed by C3, C4 and C1

  14. Efficiency of the coherent biexciton admixture mechanism for multiple exciton generation in InAs nanocrystals

    International Nuclear Information System (INIS)

    We study the coherent mixing between two-particle (single exciton) and four-particle (biexciton) states of a semiconductor nanocrystal resulting from the Coulomb coupling between states with different numbers of electron-hole pairs. Using a simple model of the nanocrystal wave functions and an envelope function approach, we estimate the efficiency of the multiple exciton generation (MEG) process resulting from such coherent admixture mechanism, including all the relevant states in a very broad energy interval. We show that in a typical ensemble of nanocrystals with an average radius of 3nm, the onset of the MEG process appears about 1 eV above the lower edge of the biexciton density of states. This is due to the angular momentum conservation that imposes selection rules and limits the available MEG pathways, thus taking over the role of momentum conservation that hinders this process in bulk. The efficiency of the MEG process reaches 50% for photon energies around 5 eV. The MEG onset shifts to lower energies and therefore the efficiency increases in a certain energy range as the radius grows. The energy dependence of the MEG efficiency differs considerably between ensembles with small and large inhomogeneity of nanocrystal sizes. (paper)

  15. Dynamics of fragmentation and multiple vacancy generation in irradiated single-walled carbon nanotubes

    CERN Document Server

    Javeed, Sumera; Ahmad, Shoaib

    2016-01-01

    The results from mass spectrometry of clusters sputtered from Cs+ irradiated single-walled carbon nano-tubes (SWCNTs) as a function of energy and dose identify the nature of the resulting damage in the form of multiple vacancy generation. For pristine SWCNTs at all Cs+ energies, C2 is the most dominant species, followed by C3, C4 and C1. The experiments were performed in three stages: in the first stage, Cs+ energy E(Cs+) was varied. During the second stage, the nanotubes were irradiated continuously at E(Cs+) = 5 keV for 1,800 s. Afterwards, the entire sequence of irradiation energies was repeated to differentiate between the fragmentation patterns of the pristine and of heavily irradiated SWCNTs. The sputtering and normalized yields identify the quantitative and relative extent of the ion-induced damage by creating double, triple and quadruple vacancies; the single vacancies are least favored. Sputtering from the heavily irradiated SWCNTs occurs not only from the damaged and fragmented nanotubes, but also f...

  16. Study of thermal hydraulic behaviors during steam generator multiple tube rupture events in PWR

    International Nuclear Information System (INIS)

    Since the occurrence probability of multiple steam generator tube rupture (MSGTR) in PWR is low, analytical or experimental investigation for termination of such accidents is not performed explicitly. Therefore, thermal-hydraulic analysis of the plant behavior under the MSGTR (10 and 50 tubes) in all loops or in a single loop with station black out (SBO) were made in this study with use of the code RETRAN3D, and investigations for accident management (AM) of such accidents were made in order to contribute to continuous risk reduction efforts in the future. This study indicated that the water supply function to the SG is quite important for coping with accidents involving MSGTR accompanied by SBO to prevent core damage. Further, if the auxiliary feed water system loses its function, the time to reach the core exposure is predicted to be reduced by 1 hour or more in a MSGTR case as compared to a single-tube SGTR case. Therefore, in order to prevent the core damage during MSGTR, it is desirable to have alternative water injection equipment operable to quickly replace auxiliary feed water system if it fails and to increase the reliability of the auxiliary feed water system. (author)

  17. Cytokine-mediated regulation of plasma cell generation: IL-21 takes center stage

    Directory of Open Access Journals (Sweden)

    Stuart G Tangye

    2014-02-01

    Full Text Available During our life we are surrounded by continuous threats from a diverse range of invading pathogens. Our immune system has evolved multiple mechanisms to efficiently deal with these threats to prevent them causing disease. Differentiation of mature B cells into plasma cells (PC - the antibody (Ab secreting cells of the immune system - is critical for the generation of protective and long-lived humoral immune responses. Indeed, efficient production of antigen (Ag-specific Ab underlies the success of most currently available vaccines. The mature B cell pool is composed of several subsets, distinguished from one according to size, surface marker expression, location and Ag exposure, and they all have the capacity to differentiate into PCs. For a B cell to acquire the capacity to produce Abs, it must undergo an extensive differentiation process driven by changes in gene expression. Two broad categories of Ag exist that cause B cell activation and differentiation: T cell dependent (TD or T cell independent (TI. In addition to the B cell subset and nature of the Ag, it is important to consider the cytokine environment that also influences how B cell differentiation is achieved. Thus, while many cytokines can induce Ab secretion by B cells after activation with mimics of TD and TI stimuli in vitro, they can have different efficacies and specificities, and can often preferentially induce production of one Ig isotype over another. Here, we will provide an overview of in vitro studies (mouse and human origin that evaluated the role the different cytokines in inducing the differentiation of distinct B cell subsets to the PC lineage. We will place particular emphasis on IL-21, which has emerged as the most potent inducer of terminal B cell differentiation in humans. We will also focus on the role of IL-21 and defects in B-cell function and how these contribute to human immunopathologies such as primary immunodeficiencies and B-cell mediated autoimmune

  18. Continuous-variable quantum teleportation with non-Gaussian entangled states generated via multiple-photon subtraction and addition

    CERN Document Server

    Wang, Shuai; Chen, Xian-Feng; Xu, Xue-Fen

    2014-01-01

    We investigate the Einstein-Podolsky-Rosen correlation (EPR), the quadrature squeezing and the continuous variable quantum teleportation when considering non-Gaussian entangled states generated by applying multiple-photon addition and multiple-photon subtraction to a two-mode squeezed vacuum state (TMSVs). Our results indicate that, in the case of symmetric multiple-photon-subtracted TMSVs, the corresponding EPR correlation, the two-mode squeezing, the sum squeezing and the fidelity of teleporting a coherent state and a squeezed vacuum state can be enhanced for any squeezing parameter $r$, and these enhancements increase with the number of the operations in small-squeezing regime. While asymmetric multiple-photon subtractions will generally reduce these quantities. For the multiple-photon added TMSVs, although it holds stronger entanglement, its EPR correlation, two-mode squeezing, sum squeezing and the fidelity of a coherent state are always smaller than that of the TMSVs. Only when considering teleporting a...

  19. Glycogen Synthase Kinase-3 regulates multiple myeloma cell growth and bortezomib-induced cell death

    Directory of Open Access Journals (Sweden)

    Colpo Anna

    2010-10-01

    Full Text Available Abstract Background Glycogen Synthase Kinase-3 (GSK-3 α and β are two serine-threonine kinases controlling insulin, Wnt/β-catenin, NF-κB signaling and other cancer-associated transduction pathways. Recent evidence suggests that GSK-3 could function as growth-promoting kinases, especially in malignant cells. In this study, we have investigated GSK-3α and GSK-3β function in multiple myeloma (MM. Methods GSK-3 α and β expression and cellular localization were investigated by Western blot (WB and immunofluorescence analysis in a panel of MM cell lines and in freshly isolated plasma cells from patients. MM cell growth, viability and sensitivity to bortezomib was assessed upon treatment with GSK-3 specific inhibitors or transfection with siRNAs against GSK-3 α and β isoforms. Survival signaling pathways were studied with WB analysis. Results GSK-3α and GSK-3β were differently expressed and phosphorylated in MM cells. Inhibition of GSK-3 with the ATP-competitive, small chemical compounds SB216763 and SB415286 caused MM cell growth arrest and apoptosis through the activation of the intrinsic pathway. Importantly, the two inhibitors augmented the bortezomib-induced MM cell cytotoxicity. RNA interference experiments showed that the two GSK-3 isoforms have distinct roles: GSK-3β knock down decreased MM cell viability, while GSK-3α knock down was associated with a higher rate of bortezomib-induced cytotoxicity. GSK-3 inhibition caused accumulation of β-catenin and nuclear phospho-ERK1, 2. Moreover, GSK-3 inhibition and GSK-3α knockdown enhanced bortezomib-induced AKT and MCL-1 protein degradation. Interestingly, bortezomib caused a reduction of GSK-3 serine phosphorylation and its nuclear accumulation with a mechanism that resulted partly dependent on GSK-3 itself. Conclusions These data suggest that in MM cells GSK-3α and β i play distinct roles in cell survival and ii modulate the sensitivity to proteasome inhibitors.

  20. High-order harmonics generated from single and multiple molecular orbits in mid-infrared laser fields

    Directory of Open Access Journals (Sweden)

    ZHANG Jingtao

    2015-08-01

    Full Text Available High-order harmonics generated from aligned molecules are studied by a nonperturbative QED theory and the effect of the multiple molecular orbits is included.The harmonic spectra generated from single molecular orbit exhibit an interference minimum which is induced by the molecular structure.The location of the spectral minimum shifts with the laser intensity in long laser pulses,but is fixed in ultrashort laser pulses.This difference is owed to the quiver motion of the electron in the laser pulses.The maximal shift of the spectral minimum equals to the increment of the ponderomotive energy and depends linearly on the laser intensity.The interference between the harmonics generated from multiple molecular orbits has two principal effects:one is obscuring the deep minima in the overall harmonic spectrum,the other is manifesting the phase jump in the harmonics generated from single molecular orbit.

  1. Single cell analysis of yeast replicative aging using a new generation of microfluidic device.

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    Full Text Available A major limitation to yeast aging study has been the inability to track mother cells and observe molecular markers during the aging process. The traditional lifespan assay relies on manual micro-manipulation to remove daughter cells from the mother, which is laborious, time consuming, and does not allow long term tracking with high resolution microscopy. Recently, we have developed a microfluidic system capable of retaining mother cells in the microfluidic chambers while removing daughter cells automatically, making it possible to observe fluorescent reporters in single cells throughout their lifespan. Here we report the development of a new generation of microfluidic device that overcomes several limitations of the previous system, making it easier to fabricate and operate, and allowing functions not possible with the previous design. The basic unit of the device consists of microfluidic channels with pensile columns that can physically trap the mother cells while allowing the removal of daughter cells automatically by the flow of the fresh media. The whole microfluidic device contains multiple independent units operating in parallel, allowing simultaneous analysis of multiple strains. Using this system, we have reproduced the lifespan curves for the known long and short-lived mutants, demonstrating the power of the device for automated lifespan measurement. Following fluorescent reporters in single mother cells throughout their lifespan, we discovered a surprising change of expression of the translation elongation factor TEF2 during aging, suggesting altered translational control in aged mother cells. Utilizing the capability of the new device to trap mother-daughter pairs, we analyzed mother-daughter inheritance and found age dependent asymmetric partitioning of a general stress response reporter between mother and daughter cells.

  2. Genomic definition of multiple ex vivo regulatory T cell subphenotypes

    OpenAIRE

    Feuerer, Markus; Hill, Jonathan A.; Kretschmer, Karsten; von Boehmer, Harald; Mathis, Diane; Benoist, Christophe

    2010-01-01

    Regulatory T (Treg) cells that express the Foxp3 transcription factor are essential for lymphoid homeostasis and immune tolerance to self. Other nonimmunological functions of Treg cells, such as controlling metabolic function in adipose tissue, are also emerging. Treg cells originate primarily in the thymus, but can also be elicited from conventional T cells by in vivo exposure to low-dose antigen or homeostatic expansion or by activation in the presence of TGFβ in vitro. Treg cells are chara...

  3. Generation of Human Induced Pluripotent Stem Cells from Peripheral Blood Mononuclear Cells Using Sendai Virus.

    Science.gov (United States)

    Soares, Filipa A C; Pedersen, Roger A; Vallier, Ludovic

    2016-01-01

    This protocol describes the efficient isolation of peripheral blood mononuclear cells from circulating blood via density gradient centrifugation and subsequent generation of integration-free human induced pluripotent stem cells. Peripheral blood mononuclear cells are cultured for 9 days to allow expansion of the erythroblast population. The erythroblasts are then used to derive human induced pluripotent stem cells using Sendai viral vectors, each expressing one of the four reprogramming factors Oct4, Sox2, Klf4, and c-Myc.

  4. 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...

  5. Generation of Neurospheres from Human Adipose-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Erfang Yang

    2015-01-01

    Full Text Available Transplantation of neural stem cells (NSCs to treat neurodegenerative disease shows promise; however, the clinical application of NSCs is limited by the invasive procurement and ethical concerns. Adipose-derived stem cells (ADSCs are a source of multipotent stem cells that can self-renew and differentiate into various kinds of cells; this study intends to generate neurospheres from human ADSCs by culturing ADSCs on uncoated culture flasks in serum-free neurobasal medium supplemented with B27, basic fibroblast growth factor (bFGF, and epidermal growth factor (EGF; the ADSCs-derived neurospheres were terminally differentiated after growth factor withdrawal. Expression of Nestin, NeuN, MAP2, and GFAP in ADSCs and terminally differentiated neurospheres was shown by quantitative reverse transcription-polymerase chain reaction (qRT-PCR, western blotting, and immunocytochemistry; cell proliferation in neurospheres was evaluated by cell cycle analyses, immunostaining, and flow cytometry. These data strongly support the conclusion that human ADSCs can successfully differentiate into neurospheres efficiently on uncoated culture flasks, which present similar molecular marker pattern and proliferative ability with NSCs derived from embryonic and adult brain tissues. Therefore, human ADSCs may be an ideal alternative source of stem cells for the treatment of neurodegenerative diseases.

  6. A Bio-Based Fuel Cell for Distributed Energy Generation

    Energy Technology Data Exchange (ETDEWEB)

    Anthony Terrinoni; Sean Gifford

    2008-06-30

    The technology we propose consists primarily of an improved design for increasing the energy density of a certain class of bio-fuel cell (BFC). The BFCs we consider are those which harvest electrons produced by microorganisms during their metabolism of organic substrates (e.g. glucose, acetate). We estimate that our technology will significantly enhance power production (per unit volume) of these BFCs, to the point where they could be employed as stand-alone systems for distributed energy generation.

  7. Sustained Arc expression in adult-generated granule cells.

    Science.gov (United States)

    Meconi, Alicia; Lui, Erika; Marrone, Diano F

    2015-08-31

    The dentate gyrus (DG) plays a critical role in memory formation and maintenance. Fitting this specialized role, the DG has many unique characteristics. In addition to being one of the few places in which new neurons are continually added in adulthood, the region also shows a unique long-term sustained transcriptional response of the immediate-early gene Arc to sensory input. Although we know that adult-generated granule cells are reliably recruited into behaviorally-driven neuronal network, it remains unknown whether they display robust late-phase sustained transcription in response to activity like their developmentally-generated counterparts. Since this late-phase of transcription is required for enduring plasticity, knowing if sustained transcription appears as soon as these cells are incorporated provides information on their potential for plasticity. To address this question, adult F344 rats were injected with BrdU (50mg/kg/day for 5 days) and 4 weeks later explored a novel environment. Arc expression in both BrdU- and BrdU+ neurons was determined 0.5h, 1h, 2h, 6h, 8h, 12h, or 24h following this behavior. Recently-generated granule cells showed a robust sustained Arc expression following a discrete behavioral experience. These data provide information on a potential mechanism to sculpt the representations of events occurring within hours of each other to create uncorrelated representations of episodes despite a highly excitable population of neurons. PMID:26219984

  8. Increased T cell expression of CD154 (CD40-ligand) in multiple sclerosis

    DEFF Research Database (Denmark)

    Jensen, J; Krakauer, M; Sellebjerg, F

    2001-01-01

    CD154 (CD40-ligand, gp39), expressed on activated T cells, is crucial in T cell-dependent immune responses and may be involved in the pathogenesis of multiple sclerosis (MS). We studied cerebro-spinal fluid and peripheral blood T cell expression of CD154 in MS by flow cytometry. Patients with sec......CD154 (CD40-ligand, gp39), expressed on activated T cells, is crucial in T cell-dependent immune responses and may be involved in the pathogenesis of multiple sclerosis (MS). We studied cerebro-spinal fluid and peripheral blood T cell expression of CD154 in MS by flow cytometry. Patients...

  9. Regulatory T cell number in multiple sclerosis patients: A meta-analysis.

    Science.gov (United States)

    Noori-Zadeh, Ali; Mesbah-Namin, Seyed Alireza; Bistoon-Beigloo, Sara; Bakhtiyari, Salar; Abbaszadeh, Hojjat-Allah; Darabi, Shahram; Rajabibazl, Masoumeh; Abdanipour, Alireza

    2016-01-01

    Regulatory T cells (Treg cells), defined as CD4(+) CD25(+) FoxP3(+) T cells by expression of CD4, high-affinity IL-2 receptor and the transcription factor, forkhead box P3 (FoxP3). They play a pivotal role in protecting individuals from autoimmunity and a growing body of evidence suggests their role in the prevention of multiple sclerosis development. However, there are discrepancies about the type of defect in the Treg cells of multiple sclerosis patients and especially whether the Treg number alteration could be contributed to multiple sclerosis pathogenesis. Indeed, whether low number of Treg cells can be a risk factor contributing to multiple sclerosis pathogenesis is the matter of debate and there is not any comprehensive agreement on it. Thus, the objective of this systematic review and meta-analysis was to precisely quantify the nature and magnitude of the association between Treg cell number and the risk ratio/odds ratio (OR) of multiple sclerosis in the case-control studies. Hence, medical databases of Embase, PubMed/Medline, PubMed, PubMed Central and SCOPUS were searched for empirical papers using "Regulatory T cell frequency", "Treg frequency" in combination with "multiple sclerosis". In the case-control studies, papers were reviewed for inclusion/exclusion criteria and 8 publications were included. Under random-effect model meta-analysis the data showed that the frequency of Treg cells was not a risk factor in multiple sclerosis using current laboratory methods.

  10. Generation of functional podocytes from human induced pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Osele Ciampi

    2016-07-01

    Full Text Available Generating human podocytes in vitro could offer a unique opportunity to study human diseases. Here, we describe a simple and efficient protocol for obtaining functional podocytes in vitro from human induced pluripotent stem cells. Cells were exposed to a three-step protocol, which induced their differentiation into intermediate mesoderm, then into nephron progenitors and, finally, into mature podocytes. After differentiation, cells expressed the main podocyte markers, such as synaptopodin, WT1, α-Actinin-4, P-cadherin and nephrin at the protein and mRNA level, and showed the low proliferation rate typical of mature podocytes. Exposure to Angiotensin II significantly decreased the expression of podocyte genes and cells underwent cytoskeleton rearrangement. Cells were able to internalize albumin and self-assembled into chimeric 3D structures in combination with dissociated embryonic mouse kidney cells. Overall, these findings demonstrate the establishment of a robust protocol that, mimicking developmental stages, makes it possible to derive functional podocytes in vitro.

  11. Generation of airway epithelial cells with native characteristics from mouse induced pluripotent stem cells.

    Science.gov (United States)

    Yoshie, Susumu; Imaizumi, Mitsuyoshi; Nakamura, Ryosuke; Otsuki, Koshi; Ikeda, Masakazu; Nomoto, Yukio; Wada, Ikuo; Omori, Koichi

    2016-05-01

    Airway epithelial cells derived from induced pluripotent stem (iPS) cells are expected to be a useful source for the regeneration of airway epithelium. Our preliminary study of embryoid body (EB) formation and the air-liquid interface (ALI) method suggested that mouse iPS cells can differentiate into airway epithelial cells. However, whether the cells generated from mouse iPS cells had the character and phenotype of native airway epithelial cells remained uninvestigated. In this study, we generated airway epithelial cells from EBs by culturing them under serum-free conditions supplemented with Activin and bFGF and by the ALI method and characterized the iPS cell-derived airway epithelial cells in terms of their gene expression, immunoreactivity, morphology, and function. Analysis by quantitative real-time reverse transcription-polymerase chain reaction(RT-PCR) revealed that the expression of the undifferentiated cell marker Nanog decreased time-dependently after the induction of differentiation, whereas definitive endoderm markers Foxa2 and Cxcr4 were transiently up-regulated. Thereafter, the expression of airway epithelium markers such as Tubb4a, Muc5ac, and Krt5 was detected by RT-PCR and immunostaining. The formation of tight junctions was also confirmed by immunostaining and permeability assay. Analysis by hematoxylin and eosin staining and scanning electron microscopy indicated that the cells generated from mouse iPS cells formed airway-epithelium-like tissue and had cilia, the movement of which was visualized and observed to be synchronized. These results demonstrate that the airway epithelial cells generated by our method have native characteristics and open new perspectives for the regeneration of injured airway epithelium. PMID:26590823

  12. 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

  13. 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.

  14. Myeloid derived suppressor cells in multiple myeloma: preclinical research and translational opportunities

    Directory of Open Access Journals (Sweden)

    Cirino eBotta

    2014-12-01

    Full Text Available Immunosuppressive cells have been reported to play an important role in tumor progression mainly because of their capability to promote immune-escape, angiogenesis and metastasis. Among them, myeloid derived suppressor cells (MDSCs have been recently identified as immature myeloid cells, induced by tumor-associated inflammation, able to impair both innate and adaptive immunity. While murine MDSCs are usually identified by the expression of CD11b and Gr-1, human MDSCs represent a more heterogeneous population characterized by the expression of CD33 and CD11b, low or no HLA-DR and variable CD14 and CD15. In particular, the last two may alternatively identify monocyte-like or granulocyte-like MDSC subsets with different immunosuppressive properties. Recently, a substantial increase of MDSCs has been found in peripheral blood and bone marrow (BM of multiple myeloma (MM patients with a role in disease progression and/or drug resistance. Preclinical models recapitulating the complexity of the MM-related BM microenvironment (BMM are major tools for the study of the interactions between MM cells and cells of the BMM (including MDSCs and for the development of new agents targeting MM-associated immune suppressive cells.This review will focus on current strategies for human MDSCs generation and investigation of their immunosuppressive function in vitro and in vivo, taking into account the relevant relationship occurring within the MM-BMM. We will then provide trends in MDSC-associated research and suggest potential application for the treatment of MM.

  15. Generation and characterization of functional cardiomyocytes derived from human T cell-derived induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Tomohisa Seki

    Full Text Available Induced pluripotent stem cells (iPSCs have been proposed as novel cell sources for genetic disease models and revolutionary clinical therapies. Accordingly, human iPSC-derived cardiomyocytes are potential cell sources for cardiomyocyte transplantation therapy. We previously developed a novel generation method for human peripheral T cell-derived iPSCs (TiPSCs that uses a minimally invasive approach to obtain patient cells. However, it remained unknown whether TiPSCs with genomic rearrangements in the T cell receptor (TCR gene could differentiate into functional cardiomyocyte in vitro. To address this issue, we investigated the morphology, gene expression pattern, and electrophysiological properties of TiPSC-derived cardiomyocytes differentiated by floating culture. RT-PCR analysis and immunohistochemistry showed that the TiPSC-derived cardiomyocytes properly express cardiomyocyte markers and ion channels, and show the typical cardiomyocyte morphology. Multiple electrode arrays with application of ion channel inhibitors also revealed normal electrophysiological responses in the TiPSC-derived cardiomyocytes in terms of beating rate and the field potential waveform. In this report, we showed that TiPSCs successfully differentiated into cardiomyocytes with morphology, gene expression patterns, and electrophysiological features typical of native cardiomyocytes. TiPSCs-derived cardiomyocytes obtained from patients by a minimally invasive technique could therefore become disease models for understanding the mechanisms of cardiac disease and cell sources for revolutionary cardiomyocyte therapies.

  16. Comparison of Monte-Carlo generator predictions for gap fraction and jet multiplicity observables in t anti t events

    Energy Technology Data Exchange (ETDEWEB)

    Bruscino, Nello; Cristinziani, Markus; Ghneimat, Mazuza; Heer, Sebastian; Kostyukhin, Vadim; Machefer, Evan; Mijovic, Liza; Yau Wong, Kaven [Physikalisches Institut, Universitaet Bonn (Germany)

    2015-07-01

    Predictions from several Monte-Carlo generators are compared for the t anti t production. The predictions are also compared to the data taken by ATLAS in 2011 at √(s)=7 TeV. The focus is on observables sensitive to additional parton radiation: jet multiplicities and gap fraction observables. Generators that have been used for ATLAS analyses of the data collected in the first LHC proton physics run as well as new generators that will be used in the upcoming LHC run are included. The goal of the work is to collect information and studies for discussions between the communities of the ATLAS and CMS experiments and colleagues from theory.

  17. An internal ribosome entry site (IRES mutant library for tuning expression level of multiple genes in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Esther Y C Koh

    Full Text Available A set of mutated Encephalomyocarditis virus (EMCV internal ribosome entry site (IRES elements with varying strengths is generated by mutating the translation initiation codons of 10(th, 11(th, and 12(th AUG to non-AUG triplets. They are able to control the relative expression of multiple genes over a wide range in mammalian cells in both transient and stable transfections. The relative strength of each IRES mutant remains similar in different mammalian cell lines and is not gene specific. The expressed proteins have correct molecular weights. Optimization of light chain over heavy chain expression by these IRES mutants enhances monoclonal antibody expression level and quality in stable transfections. Uses of this set of IRES mutants can be extended to other applications such as synthetic biology, investigating interactions between proteins and its complexes, cell engineering, multi-subunit protein production, gene therapy, and reprogramming of somatic cells into stem cells.

  18. Generation of retinal pigment epithelial cells from human embryonic stem cell-derived spherical neural masses.

    Science.gov (United States)

    Cho, Myung Soo; Kim, Sang Jin; Ku, Seung-Yup; Park, Jung Hyun; Lee, Haksup; Yoo, Dae Hoon; Park, Un Chul; Song, Seul Ae; Choi, Young Min; Yu, Hyeong Gon

    2012-09-01

    Dysfunction and loss of retinal pigment epithelium (RPE) are major pathologic changes observed in various retinal degenerative diseases such as aged-related macular degeneration. RPE generated from human pluripotent stem cells can be a good candidate for RPE replacement therapy. Here, we show the differentiation of human embryonic stem cells (hESCs) toward RPE with the generation of spherical neural masses (SNMs), which are pure masses of hESCs-derived neural precursors. During the early passaging of SNMs, cystic structures arising from opened neural tube-like structures showed pigmented epithelial morphology. These pigmented cells were differentiated into functional RPE by neuroectodermal induction and mechanical purification. Most of the differentiated cells showed typical RPE morphologies, such as a polygonal-shaped epithelial monolayer, and transmission electron microscopy revealed apical microvilli, pigment granules, and tight junctions. These cells also expressed molecular markers of RPE, including Mitf, ZO-1, RPE65, CRALBP, and bestrophin. The generated RPE also showed phagocytosis of isolated bovine photoreceptor outer segment and secreting pigment epithelium-derived factor and vascular endothelial growth factor. Functional RPE could be generated from SNM in our method. Because SNMs have several advantages, including the capability of expansion for long periods without loss of differentiation capability, easy storage and thawing, and no need for feeder cells, our method for RPE differentiation may be used as an efficient strategy for generating functional RPE cells for retinal regeneration therapy.

  19. Generation of retinal pigment epithelial cells from human embryonic stem cell-derived spherical neural masses.

    Science.gov (United States)

    Cho, Myung Soo; Kim, Sang Jin; Ku, Seung-Yup; Park, Jung Hyun; Lee, Haksup; Yoo, Dae Hoon; Park, Un Chul; Song, Seul Ae; Choi, Young Min; Yu, Hyeong Gon

    2012-09-01

    Dysfunction and loss of retinal pigment epithelium (RPE) are major pathologic changes observed in various retinal degenerative diseases such as aged-related macular degeneration. RPE generated from human pluripotent stem cells can be a good candidate for RPE replacement therapy. Here, we show the differentiation of human embryonic stem cells (hESCs) toward RPE with the generation of spherical neural masses (SNMs), which are pure masses of hESCs-derived neural precursors. During the early passaging of SNMs, cystic structures arising from opened neural tube-like structures showed pigmented epithelial morphology. These pigmented cells were differentiated into functional RPE by neuroectodermal induction and mechanical purification. Most of the differentiated cells showed typical RPE morphologies, such as a polygonal-shaped epithelial monolayer, and transmission electron microscopy revealed apical microvilli, pigment granules, and tight junctions. These cells also expressed molecular markers of RPE, including Mitf, ZO-1, RPE65, CRALBP, and bestrophin. The generated RPE also showed phagocytosis of isolated bovine photoreceptor outer segment and secreting pigment epithelium-derived factor and vascular endothelial growth factor. Functional RPE could be generated from SNM in our method. Because SNMs have several advantages, including the capability of expansion for long periods without loss of differentiation capability, easy storage and thawing, and no need for feeder cells, our method for RPE differentiation may be used as an efficient strategy for generating functional RPE cells for retinal regeneration therapy. PMID:22683799

  20. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    International Nuclear Information System (INIS)

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma

  1. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Er-Wen [Guangzhou Institute of Forensic Science, Guangzhou (China); Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Xue, Sheng-Jiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Li, Xiao-Yan [Department of Pharmacy, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xu, Suo-Wen [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Cheng, Jian-Ding; Zheng, Jin-Xiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong [Guangzhou Institute of Forensic Science, Guangzhou (China); Li, Jie, E-mail: mdlijie@sina.com [Department of Anaesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Liu, Chao, E-mail: liuchaogaj@21cn.com [Guangzhou Institute of Forensic Science, Guangzhou (China)

    2014-05-02

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.

  2. A Case Report of Multiple Basal Cell Carcinoma Syndrome

    Directory of Open Access Journals (Sweden)

    A. Ansar

    2007-01-01

    Full Text Available Introduction: Nevoid BCC syndrome (Gorline syndrome is a familial disorder with autosomal dominant inheritense. This syndrome is combination of multiple BCC that occurs at an early age, characteristic faces with: frontal bossing, broad nasal bridge and hypertelorism, jaw cysts, palmoplanter pitting, macrocephaly, skeletal and spinal anomalies include bifid ribes, cervical rib and kyphoscoliosis, CNS abnormality include corpus callusom disgenesia , falx cerebri calcification(at early age and mental deficiency.Case Report: This case was a 25-years-old female presented with multiple and progressive skin lesions with different size in neck, upper trunk and axilla (multiple BCC, palmoplantar pitting, jaw cyst, cervical rib, bifid rib and liver haemangioma.Conclusion: With combination of clinical feature, histopathological reports of skin lesions and radiological reports of mandibular cyst and ribs anomalies, this case was diagnosed as nevoid BCC syndrome.

  3. On generating cell exemplars for detection of mitotic cells in breast cancer histopathology images.

    Science.gov (United States)

    Aloraidi, Nada A; Sirinukunwattana, Korsuk; Khan, Adnan M; Rajpoot, Nasir M

    2014-01-01

    Mitotic activity is one of the main criteria that pathologists use to decide the grade of the cancer. Computerised mitotic cell detection promises to bring efficiency and accuracy into the grading process. However, detection and classification of mitotic cells in breast cancer histopathology images is a challenging task because of the large intra-class variation in the visual appearance of mitotic cells in various stages of cell division life cycle. In this paper, we test the hypothesis that cells in histopathology images can be effectively represented using cell exemplars derived from sub-images of various kinds of cells in an image for the purposes of mitotic cell classification. We compare three methods for generating exemplar cells. The methods have been evaluated in terms of classification performance on the MITOS dataset. The experimental results demonstrate that eigencells combined with support vector machines produce reasonably high detection accuracy among all the methods.

  4. The ROCK inhibitor Y-27632 improves recovery of human embryonic stem cells after fluorescence-activated cell sorting with multiple cell surface markers.

    Directory of Open Access Journals (Sweden)

    Nil Emre

    Full Text Available BACKGROUND: Due to the inherent sensitivity of human embryonic stem cells (hESCs to manipulations, the recovery and survival of hESCs after fluorescence-activated cell sorting (FACS can be low. Additionally, a well characterized and robust methodology for performing FACS on hESCs using multiple-cell surface markers has not been described. The p160-Rho-associated coiled kinase (ROCK inhibitor, Y-27632, previously has been identified as enhancing survival of hESCs upon single-cell dissociation, as well as enhancing recovery from cryopreservation. Here we examined the application of Y-27632 to hESCs after FACS to improve survival in both feeder-dependent and feeder-independent growth conditions. METHODOLOGY/PRINCIPAL FINDINGS: HESCs were sorted using markers for SSEA-3, TRA-1-81, and SSEA-1. Cells were plated after sorting for 24 hours in either the presence or the absence of Y-27632. In both feeder-dependent and feeder-independent conditions, cell survival was greater when Y-27632 was applied to the hESCs after sort. Specifically, treatment of cells with Y-27632 improved post-sort recovery up to four fold. To determine the long-term effects of sorting with and without the application of Y-27632, hESCs were further analyzed. Specifically, hESCs sorted with and without the addition of Y-27632 retained normal morphology, expressed hESC-specific markers as measured by immunocytochemistry and flow cytometry, and maintained a stable karyotype. In addition, the hESCs could differentiate into three germ layers in vitro and in vivo in both feeder-dependent and feeder-independent growth conditions. CONCLUSIONS/SIGNIFICANCE: The application of Y-27632 to hESCs after cell sorting improves cell recovery with no observed effect on pluripotency, and enables the consistent recovery of hESCs by FACS using multiple surface markers. This improved methodology for cell sorting of hESCs will aid many applications such as removal of hESCs from secondary cell types

  5. Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells.

    Directory of Open Access Journals (Sweden)

    Karl Gledhill

    Full Text Available The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes.

  6. Efficient and cost-effective generation of mature neurons from human induced pluripotent stem cells.

    Science.gov (United States)

    Badja, Cherif; Maleeva, Galyna; El-Yazidi, Claire; Barruet, Emilie; Lasserre, Manon; Tropel, Philippe; Binetruy, Bernard; Bregestovski, Piotr; Magdinier, Frédérique

    2014-12-01

    For years, our ability to study pathological changes in neurological diseases has been hampered by the lack of relevant models until the recent groundbreaking work from Yamanaka's group showing that it is feasible to generate induced pluripotent stem cells (iPSCs) from human somatic cells and to redirect the fate of these iPSCs into differentiated cells. In particular, much interest has focused on the ability to differentiate human iPSCs into neuronal progenitors and functional neurons for relevance to a large number of pathologies including mental retardation and behavioral or degenerative syndromes. Current differentiation protocols are time-consuming and generate limited amounts of cells, hindering use on a large scale. We describe a feeder-free method relying on the use of a chemically defined medium that overcomes the need for embryoid body formation and neuronal rosette isolation for neuronal precursors and terminally differentiated neuron production. Four days after induction, expression of markers of the neurectoderm lineage is detectable. Between 4 and 7 days, neuronal precursors can be expanded, frozen, and thawed without loss of proliferation and differentiation capacities or further differentiated. Terminal differentiation into the different subtypes of mature neurons found in the human brain were observed. At 6-35 days after induction, cells express typical voltage-gated and ionotrophic receptors for GABA, glycine, and acetylcholine. This specific and efficient single-step strategy in a chemically defined medium allows the production of mature neurons in 20-40 days with multiple applications, especially for modeling human pathologies.

  7. Generation of functional hepatocyte-like cells from human deciduous periodontal ligament stem cells.

    Science.gov (United States)

    Vasanthan, Punitha; Jayaraman, Pukana; Kunasekaran, Wijenthiran; Lawrence, Anthony; Gnanasegaran, Nareshwaran; Govindasamy, Vijayendran; Musa, Sabri; Kasim, Noor Hayaty Abu

    2016-08-01

    Human deciduous periodontal ligament stem cells have been introduced for as an easily accessible source of stem cells from dental origin. Although recent studies have revealed the ability of these stem cells in multipotential attribute, their efficiency of hepatic lineage differentiation has not been addressed so far. The aim of this study is to investigate hepatic lineage fate competence of periodontal ligament stem cells through direct media induction. Differentiation of periodontal ligament stem cells into hepatocyte-like cells was conducted by the exposure of two phase media induction. First phase was performed in the presence of hepatocyte growth factors to induce a definitive endoderm formation. In the subsequent phase, the cells were treated with oncostatin M and dexamethosone followed by insulin and transferrin to generate hepatocyte-like cells. Hepatic-related characters of the generated hepatocyte-like cells were determined at both mRNA and protein level followed by functional assays. Foremost changes observed in the generation of hepatocyte-like cells were the morphological features in which these cells were transformed from fibroblastic shape to polygonal shape. Temporal expression of hepatic markers ranging from early endodermal up to late markers were detected in the hepatocyte-like cells. Crucial hepatic markers such as glycogen storage, albumin, and urea secretion were also shown. These findings exhibited the ability of periodontal ligament stem cells of dental origin to be directed into hepatic lineage fate. These cells can be regarded as an alternative autologous source in the usage of stem cell-based treatment for liver diseases. PMID:27379400

  8. Generation of functional hepatocyte-like cells from human deciduous periodontal ligament stem cells

    Science.gov (United States)

    Vasanthan, Punitha; Jayaraman, Pukana; Kunasekaran, Wijenthiran; Lawrence, Anthony; Gnanasegaran, Nareshwaran; Govindasamy, Vijayendran; Musa, Sabri; Kasim, Noor Hayaty Abu

    2016-08-01

    Human deciduous periodontal ligament stem cells have been introduced for as an easily accessible source of stem cells from dental origin. Although recent studies have revealed the ability of these stem cells in multipotential attribute, their efficiency of hepatic lineage differentiation has not been addressed so far. The aim of this study is to investigate hepatic lineage fate competence of periodontal ligament stem cells through direct media induction. Differentiation of periodontal ligament stem cells into hepatocyte-like cells was conducted by the exposure of two phase media induction. First phase was performed in the presence of hepatocyte growth factors to induce a definitive endoderm formation. In the subsequent phase, the cells were treated with oncostatin M and dexamethosone followed by insulin and transferrin to generate hepatocyte-like cells. Hepatic-related characters of the generated hepatocyte-like cells were determined at both mRNA and protein level followed by functional assays. Foremost changes observed in the generation of hepatocyte-like cells were the morphological features in which these cells were transformed from fibroblastic shape to polygonal shape. Temporal expression of hepatic markers ranging from early endodermal up to late markers were detected in the hepatocyte-like cells. Crucial hepatic markers such as glycogen storage, albumin, and urea secretion were also shown. These findings exhibited the ability of periodontal ligament stem cells of dental origin to be directed into hepatic lineage fate. These cells can be regarded as an alternative autologous source in the usage of stem cell-based treatment for liver diseases.

  9. Generation of Viable Cell and Biomaterial Patterns by Laser Transfer

    Science.gov (United States)

    Ringeisen, Bradley

    2001-03-01

    In order to fabricate and interface biological systems for next generation applications such as biosensors, protein recognition microarrays, and engineered tissues, it is imperative to have a method of accurately and rapidly depositing different active biomaterials in patterns or layered structures. Ideally, the biomaterial structures would also be compatible with many different substrates including technologically relevant platforms such as electronic circuits or various detection devices. We have developed a novel laser-based technique, termed matrix assisted pulsed laser evaporation direct write (MAPLE DW), that is able to direct write patterns and three-dimensional structures of numerous biologically active species ranging from proteins and antibodies to living cells. Specifically, we have shown that MAPLE DW is capable of forming mesoscopic patterns of living prokaryotic cells (E. coli bacteria), living mammalian cells (Chinese hamster ovaries), active proteins (biotinylated bovine serum albumin, horse radish peroxidase), and antibodies specific to a variety of classes of cancer related proteins including intracellular and extracellular matrix proteins, signaling proteins, cell cycle proteins, growth factors, and growth factor receptors. In addition, patterns of viable cells and active biomolecules were deposited on different substrates including metals, semiconductors, nutrient agar, and functionalized glass slides. We will present an explanation of the laser-based transfer mechanism as well as results from our recent efforts to fabricate protein recognition microarrays and tissue-based microfluidic networks.

  10. Multiple Effects of Berberine Derivatives on Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Luis Miguel Guamán Ortiz

    2014-01-01

    Full Text Available The pharmacological use of the plant alkaloid berberine is based on its antibacterial and anti-inflammatory properties; recently, anticancer activity has been attributed to this compound. To exploit this interesting feature, we synthesized three berberine derivatives, namely, NAX012, NAX014, and NAX018, and we tested their effects on two human colon carcinoma cell lines, that is, HCT116 and SW613-B3, which are characterized by wt and mutated p53, respectively. We observed that cell proliferation is more affected by cell treatment with the derivatives than with the lead compound; moreover, the derivatives proved to induce cell cycle arrest and cell death through apoptosis, thus suggesting that they could be promising anticancer drugs. Finally, we detected typical signs of autophagy in cells treated with berberine derivatives.

  11. Effector memory and central memory NY-ESO-1-specific re-directed T cells for treatment of multiple myeloma.

    Science.gov (United States)

    Schuberth, P C; Jakka, G; Jensen, S M; Wadle, A; Gautschi, F; Haley, D; Haile, S; Mischo, A; Held, G; Thiel, M; Tinguely, M; Bifulco, C B; Fox, B A; Renner, C; Petrausch, U

    2013-04-01

    The cancer-testis antigen NY-ESO-1 is a potential target antigen for immune therapy expressed in a subset of patients with multiple myeloma. We generated chimeric antigen receptors (CARs) recognizing the immunodominant NY-ESO-1 peptide 157-165 in the context of HLA-A*02:01 to re-direct autologous CD8(+) T cells towards NY-ESO-1(+) myeloma cells. These re-directed T cells specifically lysed NY-ESO-1(157-165)/HLA-A*02:01-positive cells and secreted IFNγ. A total of 40% of CCR7(-) re-directed T cells had an effector memory phenotype and 5% a central memory phenotype. Based on CCR7 cell sorting, effector and memory CAR-positive T cells were separated and CCR7(+) memory cells demonstrated after antigen-specific re-stimulation downregulation of CCR7 as sign of differentiation towards effector cells accompanied by an increased secretion of memory signature cytokines such as IL-2. To evaluate NY-ESO-1 as potential target antigen, we screened 78 bone marrow biopsies of multiple myeloma patients where NY-ESO-1 protein was found to be expressed by immunohistochemistry in 9.7% of samples. Adoptively transferred NY-ESO-1-specific re-directed T cells protected mice against challenge with endogenously NY-ESO-1-positive myeloma cells in a xenograft model. In conclusion, re-directed effector- and central memory T cells specifically recognized NY-ESO-1(157-165)/ HLA-A*02:01-positive cells resulting in antigen-specific functionality in vitro and in vivo.

  12. Extrapancreatic insulin-producing cells in multiple organs in diabetes

    OpenAIRE

    Kojima, Hideto; Fujimiya, Mineko; Matsumura, Kazuhiro; Nakahara, Tamio; Hara, Manami; Chan, Lawrence

    2004-01-01

    Insulin-producing cells normally occur only in the pancreas and thymus. Surprisingly, we found widespread insulin mRNA and protein expression in different diabetic mouse and rat models, including streptozotocin-treated mice and rats, ob/ob mice, and mice fed high-fat diets. We detected in diabetic mice proinsulin- and insulin-positive cells in the liver, adipose tissue, spleen, bone marrow, and thymus; many cells also produced glucagon, somatostatin, and pancreatic polypeptide. By in situ nuc...

  13. The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages.

    Science.gov (United States)

    Masumoto, Hidetoshi; Nakane, Takeichiro; Tinney, Joseph P; Yuan, Fangping; Ye, Fei; Kowalski, William J; Minakata, Kenji; Sakata, Ryuzo; Yamashita, Jun K; Keller, Bradley B

    2016-01-01

    Human induced pluripotent stem cells (hiPSCs) are a robust source for cardiac regenerative therapy due to their potential to support autologous and allogeneic transplant paradigms. The in vitro generation of three-dimensional myocardial tissue constructs using biomaterials as an implantable hiPSC-derived myocardium provides a path to realize sustainable myocardial regeneration. We generated engineered cardiac tissues (ECTs) from three cellular compositions of cardiomyocytes (CMs), endothelial cells (ECs), and vascular mural cells (MCs) differentiated from hiPSCs. We then determined the impact of cell composition on ECT structural and functional properties. In vitro force measurement showed that CM+EC+MC ECTs possessed preferential electromechanical properties versus ECTs without vascular cells indicating that incorporation of vascular cells augmented tissue maturation and function. The inclusion of MCs facilitated more mature CM sarcomeric structure, preferential alignment, and activated multiple tissue maturation pathways. The CM+EC+MC ECTs implanted onto infarcted, immune tolerant rat hearts engrafted, displayed both host and graft-derived vasculature, and ameliorated myocardial dysfunction. Thus, a composition of CMs and multiple vascular lineages derived from hiPSCs and incorporated into ECTs promotes functional maturation and demonstrates myocardial replacement and perfusion relevant for clinical translation. PMID:27435115

  14. Releasing dentate nucleus cells from Purkinje cell inhibition generates output from the cerebrocerebellum.

    Directory of Open Access Journals (Sweden)

    Takahiro Ishikawa

    Full Text Available The cerebellum generates its vast amount of output to the cerebral cortex through the dentate nucleus (DN that is essential for precise limb movements in primates. Nuclear cells in DN generate burst activity prior to limb movement, and inactivation of DN results in cerebellar ataxia. The question is how DN cells become active under intensive inhibitory drive from Purkinje cells (PCs. There are two excitatory inputs to DN, mossy fiber and climbing fiber collaterals, but neither of them appears to have sufficient strength for generation of burst activity in DN. Therefore, we can assume two possible mechanisms: post-inhibitory rebound excitation and disinhibition. If rebound excitation works, phasic excitation of PCs and a concomitant inhibition of DN cells should precede the excitation of DN cells. On the other hand, if disinhibition plays a primary role, phasic suppression of PCs and activation of DN cells should be observed at the same timing. To examine these two hypotheses, we compared the activity patterns of PCs in the cerebrocerebellum and DN cells during step-tracking wrist movements in three Japanese monkeys. As a result, we found that the majority of wrist-movement-related PCs were suppressed prior to movement onset and the majority of wrist-movement-related DN cells showed concurrent burst activity without prior suppression. In a minority of PCs and DN cells, movement-related increases and decreases in activity, respectively, developed later. These activity patterns suggest that the initial burst activity in DN cells is generated by reduced inhibition from PCs, i.e., by disinhibition. Our results indicate that suppression of PCs, which has been considered secondary to facilitation, plays the primary role in generating outputs from DN. Our findings provide a new perspective on the mechanisms used by PCs to influence limb motor control and on the plastic changes that underlie motor learning in the cerebrocerebellum.

  15. Development of planar solid oxide fuel cells for power generation applications

    Energy Technology Data Exchange (ETDEWEB)

    Minh, N.Q. [AlliedSignal Aerospce Equipment Systems, Torrance, CA (United States)

    1996-04-01

    Planar solid oxide fuel cells (SOFCs) are presently being developed for a variety of electric power generation application. The planar design offers simple cell geometry, high power density, and multiple fabrication and gas manifolding options. Planar SOFC technology has received much attention recently, and significant progress has been made in this area. Recent effort at AlliedSignal has focused on the development of high-performance, lightweight planar SOFCs, having thin-electrolyte films, that can be operated efficiently at reduced temperatures (< 1000{degrees}C). The advantages of reduced-temperature operation include wider material choice (including use of metallic interconnects), expected longer cell life, reduced thermal stress, improved reliability, and reduced fuel cell cost. The key aspect in the development of thin-film SIFCs is to incorporate the thin electrolyte layer into the desired structure of cells in a manner that yields the required characteristics. AlliedSignal has developed a simple and cost-effective method based on tape calendering for the fabrication of thin-electrolyte SOFCs. Thin-electrolyte cells made by tape calendering have shown extraordinary performance, e.g., producing more than 500mW/cm{sup 2} at 700{degrees}C and 800mW/cm{sup 2} at 800{degrees}C with hydrogen as fuel and air is oxidant. thin-electrolyte single cells have been incorporated into a compliant metallic stack structure and operated at reduced and operated at reduced-temperature conditions.

  16. Genetic engineering of hematopoietic stem cells to generate invariant natural killer T cells.

    Science.gov (United States)

    Smith, Drake J; Liu, Siyuan; Ji, Sunjong; Li, Bo; McLaughlin, Jami; Cheng, Donghui; Witte, Owen N; Yang, Lili

    2015-02-01

    Invariant natural killer T (iNKT) cells comprise a small population of αβ T lymphocytes. They bridge the innate and adaptive immune systems and mediate strong and rapid responses to many diseases, including cancer, infections, allergies, and autoimmunity. However, the study of iNKT cell biology and the therapeutic applications of these cells are greatly limited by their small numbers in vivo (∼0.01-1% in mouse and human blood). Here, we report a new method to generate large numbers of iNKT cells in mice through T-cell receptor (TCR) gene engineering of hematopoietic stem cells (HSCs). We showed that iNKT TCR-engineered HSCs could generate a clonal population of iNKT cells. These HSC-engineered iNKT cells displayed the typical iNKT cell phenotype and functionality. They followed a two-stage developmental path, first in thymus and then in the periphery, resembling that of endogenous iNKT cells. When tested in a mouse melanoma lung metastasis model, the HSC-engineered iNKT cells effectively protected mice from tumor metastasis. This method provides a powerful and high-throughput tool to investigate the in vivo development and functionality of clonal iNKT cells in mice. More importantly, this method takes advantage of the self-renewal and longevity of HSCs to generate a long-term supply of engineered iNKT cells, thus opening up a new avenue for iNKT cell-based immunotherapy.

  17. Generation of Bio-electricity by Microbial Fuel Cells

    Directory of Open Access Journals (Sweden)

    Maksudur R. Khan

    2012-06-01

    Full Text Available Renewable energy is an increasing need in our society. Microbial fuel cell (MFC technology represents a new technology for the regeneration of electricity from what would otherwise be considered waste and can be a vital candidate for energy in this respect. Electricity directly generated by using bacteria while accomplishing wastewater treatment in MFC processes. The present study deals with performance of proton exchange membrane and cation exchange resin for ion transfer. The effect of dimension of Resin Bridge on electricity generation and COD removal was reported. A maximum voltage of 10.5 mV was observed at 400ppm of KMnO4 along with 400ml of dairy in an anode chamber. Average COD removal was in the range of 70% to 90%.

  18. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Figueiredo, Céu; Seruca, Raquel;

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair...... pathways. As such, this review highlights the consequences of H. pylori infection on the integrity of DNA in the host cells. By down-regulating major DNA repair pathways, H. pylori infection has the potential to generate mutations. In addition, H. pylori infection can induce direct changes on the DNA...... of the host, such as oxidative damage, methylation, chromosomal instability, microsatellite instability, and mutations. Interestingly, H. pylori infection generates genetic instability in nuclear and mitochondrial DNA. Based on the reviewed literature we conclude that H. pylori infection promotes gastric...

  19. Different aspects of thalidomide treatment and stem cell transplantation in multiple myeloma patients

    NARCIS (Netherlands)

    Marion, A.M.W. van

    2006-01-01

    Multiple myeloma (MM) is an haematological malignancy caused by an unrestrained proliferation of plasma cells (monoclonally differentiated B-cells), and part of the white blood cell count. This proliferation infiltrates the blood forming skeletal bone marrow, producing osteoclastic factors, causing

  20. Insulin-producing cells generated from dedifferentiated human pancreatic beta cells expanded in vitro.

    Directory of Open Access Journals (Sweden)

    Holger A Russ

    Full Text Available BACKGROUND: Expansion of beta cells from the limited number of adult human islet donors is an attractive prospect for increasing cell availability for cell therapy of diabetes. However, attempts at expanding human islet cells in tissue culture result in loss of beta-cell phenotype. Using a lineage-tracing approach we provided evidence for massive proliferation of beta-cell-derived (BCD cells within these cultures. Expansion involves dedifferentiation resembling epithelial-mesenchymal transition (EMT. Epigenetic analyses indicate that key beta-cell genes maintain open chromatin structure in expanded BCD cells, although they are not transcribed. Here we investigated whether BCD cells can be redifferentiated into beta-like cells. METHODOLOGY/PRINCIPAL FINDING: Redifferentiation conditions were screened by following activation of an insulin-DsRed2 reporter gene. Redifferentiated cells were characterized for gene expression, insulin content and secretion assays, and presence of secretory vesicles by electron microscopy. BCD cells were induced to redifferentiate by a combination of soluble factors. The redifferentiated cells expressed beta-cell genes, stored insulin in typical secretory vesicles, and released it in response to glucose. The redifferentiation process involved mesenchymal-epithelial transition, as judged by changes in gene expression. Moreover, inhibition of the EMT effector SLUG (SNAI2 using shRNA resulted in stimulation of redifferentiation. Lineage-traced cells also gave rise at a low rate to cells expressing other islet hormones, suggesting transition of BCD cells through an islet progenitor-like stage during redifferentiation. CONCLUSIONS/SIGNIFICANCE: These findings demonstrate for the first time that expanded dedifferentiated beta cells can be induced to redifferentiate in culture. The findings suggest that ex-vivo expansion of adult human islet cells is a promising approach for generation of insulin-producing cells for

  1. Fuel cell - An alternative for power and heat generating

    International Nuclear Information System (INIS)

    One of the most promising energy generating technologies is the fuel cell (FC) because of its high efficiency and low emissions. There are even zero chemical emissions FC and cogeneration plants based on FC generate low heat emissions too. FC was invented 160 years ago but it was usually used only since 1960 in space missions. A FC farm tractor was tested 40 years ago. FC was again taken into account by power engineering since 1990 and it is now considered a credible alternative to power and heat generating. The thermal power engineers (and not only they) have two problems of cardinal importance for mankind to solve: - Energy saving (by increasing of energy generating efficiency) and - Environmental protection (by reducing chemical and heat emissions). The possibilities to use FC to generate power and heat are practically endless: on the earth, in the air and outer space, by and under water, in numberless areas of human activities. FC are now powering buses, cars, trains, boats, plains, scooters, highway road signs etc. There are already miniature FC for portable electronics. Homes, schools, hospitals, institutes, banks, police stations, etc are using FC to generate power and heat for their facilities. The methane gas produced by wastewater treatment plants and landfills is converted into electricity by using FC. Being less expensive than nuclear and solar source of energy, FC is now generally used in the space missions (in addition FC generates water). In this work an analysis of the possibilities to use FC especially for combined power and heat generating is presented. FC is favourite as energy source in space missions because it is less expensive than nuclear or solar sources. All major automobile companies have FC powered automobiles in testing stage. Mini FC for phone, laptop, and electronics are already on market. FC will be use to pagers, video recorders, small portable tools, miniature robots, special devices as hearing aid various devices, smoke detectors

  2. Novel nanostructures for next generation dye-sensitized solar cells

    KAUST Repository

    Tétreault, Nicolas

    2012-01-01

    Herein, we review our latest advancements in nanostructured photoanodes for next generation photovoltaics in general and dye-sensitized solar cells in particular. Bottom-up self-assembly techniques are developed to fabricate large-area 3D nanostructures that enable enhanced charge extraction and light harvesting through optical scattering or photonic crystal effects to improve photocurrent, photovoltage and fill factor. Using generalized techniques to fabricate specialized nanostructures enables specific optoelectronic and physical characteristics like conduction, charge extraction, injection, recombination and light harvesting but also helps improve mechanical flexibility and long-term stability in low cost materials. © 2012 The Royal Society of Chemistry.

  3. Lysophosphatidic acid induces reactive oxygen species generation by activating protein kinase C in PC-3 human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chu-Cheng; Lin, Chuan-En; Lin, Yueh-Chien [Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Ju, Tsai-Kai [Instrumentation Center, National Taiwan University, Taipei, Taiwan, ROC (China); Technology Commons, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Huang, Yuan-Li [Department of Biotechnology, Asia University, Taichung, Taiwan, ROC (China); Lee, Ming-Shyue [Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC (China); Chen, Jiun-Hong [Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Lee, Hsinyu, E-mail: hsinyu@ntu.edu.tw [Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Center for Biotechnology, National Taiwan University, Taipei, Taiwan, ROC (China); Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan, ROC (China)

    2013-11-01

    Highlights: •LPA induces ROS generation through LPA{sub 1} and LPA{sub 3}. •LPA induces ROS generation by activating PLC. •PKCζ mediates LPA-induced ROS generation. -- Abstract: Prostate cancer is one of the most frequently diagnosed cancers in males, and PC-3 is a cell model popularly used for investigating the behavior of late stage prostate cancer. Lysophosphatidic acid (LPA) is a lysophospholipid that mediates multiple behaviors in cancer cells, such as proliferation, migration and adhesion. We have previously demonstrated that LPA enhances vascular endothelial growth factor (VEGF)-C expression in PC-3 cells by activating the generation of reactive oxygen species (ROS), which is known to be an important mediator in cancer progression. Using flow cytometry, we showed that LPA triggers ROS generation within 10 min and that the generated ROS can be suppressed by pretreatment with the NADPH oxidase (Nox) inhibitor diphenylene iodonium. In addition, transfection with LPA{sub 1} and LPA{sub 3} siRNA efficiently blocked LPA-induced ROS production, suggesting that both receptors are involved in this pathway. Using specific inhibitors and siRNA, phospholipase C (PLC) and protein kinase C (PKC) were also suggested to participate in LPA-induced ROS generation. Overall, we demonstrated that LPA induces ROS generation in PC-3 prostate cancer cells and this is mediated through the PLC/PKC/Nox pathway.

  4. Development of Cells for Generation of Potential Difference from Aloe Vera

    Directory of Open Access Journals (Sweden)

    Yogendra B. Gandole

    2016-01-01

    Full Text Available Today’s need of this modern world is to introduce the renewable, sustainable, pollution free and an efficient energy sources. In this paper, some fundamental investigations are demonstrated for generating an electrical energy from living plants like Aloe Vera. The energy is generated by embedding the electrodes and cells into the plant to allow flow of ions using redox reaction. Here multiple tests have been conducted using different type of electrodes, cells and plants as an attempt to determine the characteristics of the generating system. Though the research work in this field is in infancy, we were able to produce the potential difference of about 1.221V using single pair of electrode and cell. Such hypothesis has been tested at different time of the day and different seasons of the year. Also, lots of new types of materials has been tested and used in combination to give better performance for the development of such a green energy. In future, this green energy could be used for low power electrical and electronic appliances for their operation

  5. Somatic cell reprogramming-free generation of genetically modified pigs.

    Science.gov (United States)

    Tanihara, Fuminori; Takemoto, Tatsuya; Kitagawa, Eri; Rao, Shengbin; Do, Lanh Thi Kim; Onishi, Akira; Yamashita, Yukiko; Kosugi, Chisato; Suzuki, Hitomi; Sembon, Shoichiro; Suzuki, Shunichi; Nakai, Michiko; Hashimoto, Masakazu; Yasue, Akihiro; Matsuhisa, Munehide; Noji, Sumihare; Fujimura, Tatsuya; Fuchimoto, Dai-Ichiro; Otoi, Takeshige

    2016-09-01

    Genetically modified pigs for biomedical applications have been mainly generated using the somatic cell nuclear transfer technique; however, this approach requires complex micromanipulation techniques and sometimes increases the risks of both prenatal and postnatal death by faulty epigenetic reprogramming of a donor somatic cell nucleus. As a result, the production of genetically modified pigs has not been widely applied. We provide a simple method for CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing in pigs that involves the introduction of Cas9 protein and single-guide RNA into in vitro fertilized zygotes by electroporation. The use of gene editing by electroporation of Cas9 protein (GEEP) resulted in highly efficient targeted gene disruption and was validated by the efficient production of Myostatin mutant pigs. Because GEEP does not require the complex methods associated with micromanipulation for somatic reprogramming, it has the potential for facilitating the genetic modification of pigs. PMID:27652340

  6. Somatic cell reprogramming-free generation of genetically modified pigs

    Science.gov (United States)

    Tanihara, Fuminori; Takemoto, Tatsuya; Kitagawa, Eri; Rao, Shengbin; Do, Lanh Thi Kim; Onishi, Akira; Yamashita, Yukiko; Kosugi, Chisato; Suzuki, Hitomi; Sembon, Shoichiro; Suzuki, Shunichi; Nakai, Michiko; Hashimoto, Masakazu; Yasue, Akihiro; Matsuhisa, Munehide; Noji, Sumihare; Fujimura, Tatsuya; Fuchimoto, Dai-ichiro; Otoi, Takeshige

    2016-01-01

    Genetically modified pigs for biomedical applications have been mainly generated using the somatic cell nuclear transfer technique; however, this approach requires complex micromanipulation techniques and sometimes increases the risks of both prenatal and postnatal death by faulty epigenetic reprogramming of a donor somatic cell nucleus. As a result, the production of genetically modified pigs has not been widely applied. We provide a simple method for CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing in pigs that involves the introduction of Cas9 protein and single-guide RNA into in vitro fertilized zygotes by electroporation. The use of gene editing by electroporation of Cas9 protein (GEEP) resulted in highly efficient targeted gene disruption and was validated by the efficient production of Myostatin mutant pigs. Because GEEP does not require the complex methods associated with micromanipulation for somatic reprogramming, it has the potential for facilitating the genetic modification of pigs. PMID:27652340

  7. Low-Power, Rad-hard Reconfigurable, Bi-directional Flexfet? Level Shifter ReBiLS for Multiple Generation Technology Integration for Space Exploration Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The many different generations of integrated circuit (IC) technologies required for new space exploration systems demand designs operate at multiple and often...

  8. Scheduling of Power System Cells Integrating Stochastic Power Generation

    International Nuclear Information System (INIS)

    Energy supply and climate change are nowadays two of the most outstanding problems which societies have to cope with under a context of increasing energy needs. Public awareness of these problems is driving political willingness to take actions for tackling them in a swift and efficient manner. Such actions mainly focus in increasing energy efficiency, in decreasing dependence on fossil fuels, and in reducing greenhouse gas emissions. In this context, power systems are undergoing important changes in the way they are planned and managed. On the one hand, vertically integrated structures are being replaced by market structures in which power systems are un-bundled. On the other, power systems that once relied on large power generation facilities are witnessing the end of these facilities' life-cycle and, consequently, their decommissioning. The role of distributed energy resources such as wind and solar power generators is becoming increasingly important in this context. However, the large-scale integration of such type of generation presents many challenges due, for instance, to the uncertainty associated to the variability of their production. Nevertheless, advanced forecasting tools may be combined with more controllable elements such as energy storage devices, gas turbines, and controllable loads to form systems that aim to reduce the impacts that may be caused by these uncertainties. This thesis addresses the management under market conditions of these types of systems that act like independent societies and which are herewith named power system cells. From the available literature, a unified view of power system scheduling problems is also proposed as a first step for managing sets of power system cells in a multi-cell management framework. Then, methodologies for performing the optimal day-ahead scheduling of single power system cells are proposed, discussed and evaluated under both a deterministic and a stochastic framework that directly integrates the

  9. Computer-Generated Holograms for Recording Multiple-Phase-Shifte Fiber Bragg Grating Corrugations

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A new method of fabricating multiple-phase-shifte fiber Bragg grating by CGHs is proposed. The authors present an example of such CGH by which a section multiple-phase-shifte fiber Bragg grating with two π/2 phase shifts and grating length L=21.2 μm was produced. The authors describe the production process and finally give an example of a reconstructed fiber grating with two phase-shifts.

  10. ATP release, generation and hydrolysis in exocrine pancreatic duct cells.

    Science.gov (United States)

    Kowal, J M; Yegutkin, G G; Novak, I

    2015-12-01

    Extracellular adenosine triphosphate (ATP) regulates pancreatic duct function via P2Y and P2X receptors. It is well known that ATP is released from upstream pancreatic acinar cells. The ATP homeostasis in pancreatic ducts, which secrete bicarbonate-rich fluid, has not yet been examined. First, our aim was to reveal whether pancreatic duct cells release ATP locally and whether they enzymatically modify extracellular nucleotides/sides. Second, we wished to explore which physiological and pathophysiological factors may be important in these processes. Using a human pancreatic duct cell line, Capan-1, and online luminescence measurement, we detected fast ATP release in response to pH changes, bile acid, mechanical stress and hypo-osmotic stress. ATP release following hypo-osmotic stress was sensitive to drugs affecting exocytosis, pannexin-1, connexins, maxi-anion channels and transient receptor potential cation channel subfamily V member 4 (TRPV4) channels, and corresponding transcripts were expressed in duct cells. Direct stimulation of intracellular Ca(2+) and cAMP signalling and ethanol application had negligible effects on ATP release. The released ATP was sequentially dephosphorylated through ecto-nucleoside triphosphate diphosphohydrolase (NTPDase2) and ecto-5'-nucleotidase/CD73 reactions, with respective generation of adenosine diphosphate (ADP) and adenosine and their maintenance in the extracellular medium at basal levels. In addition, Capan-1 cells express counteracting adenylate kinase (AK1) and nucleoside diphosphate kinase (NDPK) enzymes (NME1, 2), which contribute to metabolism and regeneration of extracellular ATP and other nucleotides (ADP, uridine diphosphate (UDP) and uridine triphosphate (UTP)). In conclusion, we illustrate a complex regulation of extracellular purine homeostasis in a pancreatic duct cell model involving: ATP release by several mechanisms and subsequent nucleotide breakdown and ATP regeneration via counteracting nucleotide

  11. ATP release, generation and hydrolysis in exocrine pancreatic duct cells.

    Science.gov (United States)

    Kowal, J M; Yegutkin, G G; Novak, I

    2015-12-01

    Extracellular adenosine triphosphate (ATP) regulates pancreatic duct function via P2Y and P2X receptors. It is well known that ATP is released from upstream pancreatic acinar cells. The ATP homeostasis in pancreatic ducts, which secrete bicarbonate-rich fluid, has not yet been examined. First, our aim was to reveal whether pancreatic duct cells release ATP locally and whether they enzymatically modify extracellular nucleotides/sides. Second, we wished to explore which physiological and pathophysiological factors may be important in these processes. Using a human pancreatic duct cell line, Capan-1, and online luminescence measurement, we detected fast ATP release in response to pH changes, bile acid, mechanical stress and hypo-osmotic stress. ATP release following hypo-osmotic stress was sensitive to drugs affecting exocytosis, pannexin-1, connexins, maxi-anion channels and transient receptor potential cation channel subfamily V member 4 (TRPV4) channels, and corresponding transcripts were expressed in duct cells. Direct stimulation of intracellular Ca(2+) and cAMP signalling and ethanol application had negligible effects on ATP release. The released ATP was sequentially dephosphorylated through ecto-nucleoside triphosphate diphosphohydrolase (NTPDase2) and ecto-5'-nucleotidase/CD73 reactions, with respective generation of adenosine diphosphate (ADP) and adenosine and their maintenance in the extracellular medium at basal levels. In addition, Capan-1 cells express counteracting adenylate kinase (AK1) and nucleoside diphosphate kinase (NDPK) enzymes (NME1, 2), which contribute to metabolism and regeneration of extracellular ATP and other nucleotides (ADP, uridine diphosphate (UDP) and uridine triphosphate (UTP)). In conclusion, we illustrate a complex regulation of extracellular purine homeostasis in a pancreatic duct cell model involving: ATP release by several mechanisms and subsequent nucleotide breakdown and ATP regeneration via counteracting nucleotide

  12. Acute respiratory distress syndrome due to pulmonary involvement by neoplastic plasma cells in multiple myeloma

    OpenAIRE

    Marmor, D B; Farber, J. L.; Gottlieb, J E

    2006-01-01

    Pulmonary involvement with multiple myeloma occurs infrequently and may be difficult to distinguish from more common primary lung tumours, metastatic disease, or other pleural and parenchymal abnormalities. A patient who developed acute respiratory distress syndrome (ARDS) was subsequently found to have multiple myeloma with involvement of lung parenchyma by neoplastic plasma cells. Only one other report of ARDS in association with multiple myeloma was found, and there are no previous reports...

  13. Busulfan,cyclophosphamide and etoposide as conditioning for autologous stem cell transplantation in multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    张春阳

    2013-01-01

    Objective To evaluate the efficacy and safety of dose-reduced intravenous busulfan,cyclophosphamide and etoposide(BCV)as conditioning for autologous stem cell transplantation(ASCT)in multiple myeloma(MM)

  14. Street-Experienced Peripheral B cells Traffic to the CNS in Multiple Sclerosis

    OpenAIRE

    Lu, Daniel R.; Robinson, William H

    2014-01-01

    High-throughput sequencing of immunoglobulin repertoires in patients with multiple sclerosis reveals that antigen-experienced B cells traffic between the peripheral lymph nodes and the central nervous system, suggesting the involvement of peripheral immunity in the autoimmune pathogenesis of multiple sclerosis.

  15. Enhanced performance of InGaN/GaN multiple quantum well solar cells with double indium content

    Institute of Scientific and Technical Information of China (English)

    Zhao Bi-Jun; Chen Xin; Ren Zhi-Wei; Tong Jin-Hui; Wang Xing-Fu; Li Dan-Wei; Zhuo Xiang-Jing

    2013-01-01

    The performance of a multiple quantum well (MQW) InGaN solar cell with double indium content is investigated.It is found that the adoption of a double indium structure can effectively broaden the spectral response of the external quantum efficiencies and optimize the overall performance of the solar cell.Under AM1.5G illumination,the short-circuit current density (Jsc) and conversion efficiency of the solar cell are enhanced by 65% and 13% compared with those of a normal single-indium-content MQW solar cell.These improvements are mainly attributed to the expansion of the absorption spectrum and better extraction efficiency of the photon-generated carriers induced by higher polarization.

  16. Myelin repair and functional recovery mediated by neural cell transplantation in a mouse model of multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    Lianhua Bai; Jordan Hecker; Amber Kerstetter; Robert H.Miller

    2013-01-01

    Cellular therapies are becoming a major focus for the treatment of demyelinating diseases such as multiple sclerosis (MS),therefore it is important to identify the most effective cell types that promote myelin repair.Several components contribute to the relative benefits of specific cell types including the overall efficacy of the cell therapy,the reproducibility of treatment,the mechanisms of action of distinct cell types and the ease of isolation and generation of therapeutic populations.A range of distinct cell populations promote functional recovery in animal models of MS including neural stem cells and mesenchymal stem cells derived from different tissues.Each of these cell populations has advantages and disadvantages and likely works through distinct mechanisms.The relevance of such mechanisms to myelin repair in the adult central nervous system is unclear since the therapeutic cells are generally derived from developing animals.Here we describe the isolation and characterization of a population of neural cells from the adult spinal cord that are characterized by the expression of the cell surface glycoprotein NG2.In functional studies,injection of adult NG2+ cells into mice with ongoing MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) enhanced remyelination in the CNS while the number of CD3+ T cells in areas of spinal cord demyelination was reduced approximately three-fold.In vivo studies indicated that in EAE,NG2+ cells stimulated endogenous repair while in vitro they responded to signals in areas of induced inflammation by differentiating into oligodendrocytes.These results suggested that adult NG2+ cells represent a useful cell population for promoting neural repair in a variety of different conditions including demyelinating diseases such as MS.

  17. Multiple melanocortin receptors are expressed in bone cells

    Science.gov (United States)

    Zhong, Qing; Sridhar, Supriya; Ruan, Ling; Ding, Ke-Hong; Xie, Ding; Insogna, Karl; Kang, Baolin; Xu, Jianrui; Bollag, Roni J.; Isales, Carlos M.

    2005-01-01

    Melanocortin receptors belong to the seven transmembrane domain, G-protein coupled family of receptors. There are five members of this receptor family labeled MC1R-MC5R. These receptors are activated by fragments derived from a larger molecule, proopiomelanocortin (POMC) and include ACTH, alpha beta and gamma-MSH and beta-endorphin. Because of in vitro and in vivo data suggesting direct effects of these POMC molecules on bone and bone turnover, we examined bone and bone derived cells for the presence of the various members of the melanocortin receptor family. We report that the five known melanocortin receptors are expressed to varying degrees in osteoblast-like and osteoclastic cells. POMC fragments increased proliferation and expression of a variety of genes in osteoblastic cells. Furthermore, POMC mRNA was detected in osteoclastic cells. These data demonstrate that POMC-derived peptide hormones acting through high affinity melanocortin receptors have specific effects on bone cells. Thus, in addition to the indirect effects of POMC-derived hormones on bone turnover through their modulation of steroid hormone secretion, POMC fragments may have direct and specific effects on bone cell subpopulations.

  18. Key bifurcations of bursting polyrhythms in 3-cell central pattern generators.

    Directory of Open Access Journals (Sweden)

    Jeremy Wojcik

    Full Text Available We identify and describe the key qualitative rhythmic states in various 3-cell network motifs of a multifunctional central pattern generator (CPG. Such CPGs are neural microcircuits of cells whose synergetic interactions produce multiple states with distinct phase-locked patterns of bursting activity. To study biologically plausible CPG models, we develop a suite of computational tools that reduce the problem of stability and existence of rhythmic patterns in networks to the bifurcation analysis of fixed points and invariant curves of a Poincaré return maps for phase lags between cells. We explore different functional possibilities for motifs involving symmetry breaking and heterogeneity. This is achieved by varying coupling properties of the synapses between the cells and studying the qualitative changes in the structure of the corresponding return maps. Our findings provide a systematic basis for understanding plausible biophysical mechanisms for the regulation of rhythmic patterns generated by various CPGs in the context of motor control such as gait-switching in locomotion. Our analysis does not require knowledge of the equations modeling the system and provides a powerful qualitative approach to studying detailed models of rhythmic behavior. Thus, our approach is applicable to a wide range of biological phenomena beyond motor control.

  19. Fuel cell generator with fuel electrodes that control on-cell fuel reformation

    Science.gov (United States)

    Ruka, Roswell J.; Basel, Richard A.; Zhang, Gong

    2011-10-25

    A fuel cell for a fuel cell generator including a housing including a gas flow path for receiving a fuel from a fuel source and directing the fuel across the fuel cell. The fuel cell includes an elongate member including opposing first and second ends and defining an interior cathode portion and an exterior anode portion. The interior cathode portion includes an electrode in contact with an oxidant flow path. The exterior anode portion includes an electrode in contact with the fuel in the gas flow path. The anode portion includes a catalyst material for effecting fuel reformation along the fuel cell between the opposing ends. A fuel reformation control layer is applied over the catalyst material for reducing a rate of fuel reformation on the fuel cell. The control layer effects a variable reformation rate along the length of the fuel cell.

  20. Concise review: alchemy of biology: generating desired cell types from abundant and accessible cells.

    Science.gov (United States)

    Pournasr, Behshad; Khaloughi, Keynoush; Salekdeh, Ghasem Hosseini; Totonchi, Mehdi; Shahbazi, Ebrahim; Baharvand, Hossein

    2011-12-01

    A major goal of regenerative medicine is to produce cells to participate in the generation, maintenance, and repair of tissues that are damaged by disease, aging, or trauma, such that function is restored. The establishment of induced pluripotent stem cells, followed by directed differentiation, offers a powerful strategy for producing patient-specific therapies. Given how laborious and lengthy this process can be, the conversion of somatic cells into lineage-specific stem/progenitor cells in one step, without going back to, or through, a pluripotent stage, has opened up tremendous opportunities for regenerative medicine. However, there are a number of obstacles to overcome before these cells can be widely considered for clinical applications. Here, we focus on induced transdifferentiation strategies to convert mature somatic cells to other mature cell types or progenitors, and we summarize the challenges that need to be met if the potential applications of transdifferentiation technology are to be achieved.

  1. Generation of skeletal muscle cells from pluripotent stem cells: advances and challenges.

    Science.gov (United States)

    Abujarour, Ramzey; Valamehr, Bahram

    2015-01-01

    Human pluripotent stem cells (hPSCs) possess unlimited proliferative potential while maintaining the ability to differentiate into any cell type including skeletal muscle cells (SMCs). hPSCs are amenable to genetic editing and can be derived from patient somatic cells, and thus represent a promising option for cell therapies for the treatment of degenerative diseases such as muscular dystrophies. There are unresolved challenges however associated with the derivation and scale-up of hPSCs and generation of differentiated cells in large quantity and high purity. Reported myogenic differentiation protocols are long, require cell sorting and/or rely on ectopic expression of myogenic master regulators. More recent advances have been made with the application of small molecules to enhance the myogenic differentiation efficiency and the identification of more selective markers for the enrichment of myogenic progenitors with enhanced regenerative potential. Here we review the field of myogenic differentiation and highlight areas requiring further research.

  2. Modeling and control of fuel cell based distributed generation systems

    Science.gov (United States)

    Jung, Jin Woo

    This dissertation presents circuit models and control algorithms of fuel cell based distributed generation systems (DGS) for two DGS topologies. In the first topology, each DGS unit utilizes a battery in parallel to the fuel cell in a standalone AC power plant and a grid-interconnection. In the second topology, a Z-source converter, which employs both the L and C passive components and shoot-through zero vectors instead of the conventional DC/DC boost power converter in order to step up the DC-link voltage, is adopted for a standalone AC power supply. In Topology 1, two applications are studied: a standalone power generation (Single DGS Unit and Two DGS Units) and a grid-interconnection. First, dynamic model of the fuel cell is given based on electrochemical process. Second, two full-bridge DC to DC converters are adopted and their controllers are designed: an unidirectional full-bridge DC to DC boost converter for the fuel cell and a bidirectional full-bridge DC to DC buck/boost converter for the battery. Third, for a three-phase DC to AC inverter without or with a Delta/Y transformer, a discrete-time state space circuit model is given and two discrete-time feedback controllers are designed: voltage controller in the outer loop and current controller in the inner loop. And last, for load sharing of two DGS units and power flow control of two DGS units or the DGS connected to the grid, real and reactive power controllers are proposed. Particularly, for the grid-connected DGS application, a synchronization issue between an islanding mode and a paralleling mode to the grid is investigated, and two case studies are performed. To demonstrate the proposed circuit models and control strategies, simulation test-beds using Matlab/Simulink are constructed for each configuration of the fuel cell based DGS with a three-phase AC 120 V (L-N)/60 Hz/50 kVA and various simulation results are presented. In Topology 2, this dissertation presents system modeling, modified space

  3. Very Rapid and Efficient Generation of Induced Pluripotent Stem Cells from Mouse Pre-B Cells.

    Science.gov (United States)

    Di Stefano, Bruno; Graf, Thomas

    2016-01-01

    One of the major obstacles in generating induced pluripotent stem (iPS) cells suitable for therapeutic application is the low efficiency of the process and the long time required, with many iPS lines acquiring genomic aberrations. In this chapter we describe a highly efficient iPS reprogramming system based on the transient expression in pre-B cells of the transcription factor C/EBPα, followed by the induction of the four Yamanaka factors (OSKM). In addition, the process is very rapid, yielding Oct4 positive cells within 2 days and Nanog-positive iPS cell colonies within a week.

  4. Copper anode corrosion affects power generation in microbial fuel cells

    KAUST Repository

    Zhu, Xiuping

    2013-07-16

    Non-corrosive, carbon-based materials are usually used as anodes in microbial fuel cells (MFCs). In some cases, however, metals have been used that can corrode (e.g. copper) or that are corrosion resistant (e.g. stainless steel, SS). Corrosion could increase current through galvanic (abiotic) current production or by increasing exposed surface area, or decrease current due to generation of toxic products from corrosion. In order to directly examine the effects of using corrodible metal anodes, MFCs with Cu were compared with reactors using SS and carbon cloth anodes. MFCs with Cu anodes initially showed high current generation similar to abiotic controls, but subsequently they produced little power (2 mW m-2). Higher power was produced with microbes using SS (12 mW m-2) or carbon cloth (880 mW m-2) anodes, with no power generated by abiotic controls. These results demonstrate that copper is an unsuitable anode material, due to corrosion and likely copper toxicity to microorganisms. © 2013 Society of Chemical Industry.

  5. Quantum Path Interference and Multiple Electron Scattering in Soft X-Ray High-Order Harmonic Generation

    Directory of Open Access Journals (Sweden)

    Jozsef Seres

    2015-01-01

    Full Text Available High-order harmonic generation is an important mechanism to generate coherent radiation in the few–100-eV spectral range with ultrashort laser pulses. Moreover, a closer inspection of the measured spectra provides unique information about the underlying physics and allows deriving guidelines for improvements. The long-range modulation of the spectral envelope is linked to phase matching, and we will show how to improve it with a double-pulse excitation scheme. Additionally, the spectrum contains only every fourth harmonic, which can be well explained by the quantum interference of multiple scattered electrons, and two dominant electron trajectories were selected by X-ray parametric interaction.

  6. Connecting multiple spatial scales to decode the population activity of grid cells

    OpenAIRE

    Stemmler, Martin; Mathis, Alexander; Andreas V. M Herz

    2015-01-01

    Mammalian grid cells fire when an animal crosses the points of an imaginary hexagonal grid tessellating the environment. We show how animals can navigate by reading out a simple population vector of grid cell activity across multiple spatial scales, even though neural activity is intrinsically stochastic. This theory of dead reckoning explains why grid cells are organized into discrete modules within which all cells have the same lattice scale and orientation. The lattice scale changes from m...

  7. Comparison of clinical course of patients with severe acute respiratory syndrome among the multiple generations of nosocomial transmission

    Institute of Scientific and Technical Information of China (English)

    伍卫; 王景峰; 刘品明; 江山平; 陈庆瑜; 陈为宪; 尹松梅; 严励; 詹俊; 陈锡龙; 李建国

    2004-01-01

    Background Severe acute respiratory syndrome (SARS) is characterized by both an atypical pneumonia and efficient nosocomial transmissin. However, it remains unknown whether the infectivity and the virulence of the pathogen will change throughout the successive transmission. This study was conducted to compare the clinical features and management regimens of patients with SARS among the multiple generations from nosocomial transmission initiated by a super-spreader.Methods The clinical data of 84 epidemiologically-linked SARS patients from a hospital outbreak were retrospectively studied. All patients, in whom a clear-cut transmission generation could be noted, had a direct or indirect exposure to the index patient and the epidemic successively propagated through the multiple generations of cases within a short period of time.Results There were 66 women and 18 men with mean age of (29.2 ± 10.3) years in this cluster; and 96.4% of whom were health care workers. Detailed contact tracing identified 35 (41.7%) first-generation cases, 34 (40.5%) second-generation cases, and 15 (17.8%) third-generation cases. No statistical differences among the multiple generations of transmission were found in terms of age, gender, incubation period and length of hospital stay. With the advanced transmission generations, the initial temperature lowered, the number of cases with dry cough decreased. There were no statistical differences in the peak temperature and duration of fever, other accompanying symptoms, leucopenia; however, the time from initial pulmonary infiltrates to radiographic recovery shortened (P0.05). No statistical differences were found in modes of oxygen therapy and sorts of antibiotics prescribed among the various transmission generations (P>0.05); however, as with the advanced transmission generations, the number of cases prescribed with methylprednisolone, human γ-globulin, interferon-α, antiviral drugs (oral ribavirin or oseltamivir) increased (P<0.05) and time

  8. The multiple connections between pRB and cell metabolism.

    Science.gov (United States)

    Nicolay, Brandon N; Dyson, Nicholas J

    2013-12-01

    The pRB tumor suppressor is traditionally seen as an important regulator of the cell cycle. pRB represses the transcriptional activation of a diverse set of genes by the E2F transcription factors and prevents inappropriate S-phase entry. Advances in our understanding of pRB have documented roles that extend beyond the cell cycle and this review summarizes recent studies that link pRB to the control of cell metabolism. pRB has been shown to regulate glucose tolerance, mitogenesis, glutathione synthesis, and the expression of genes involved in central carbon metabolism. Several studies have demonstrated that pRB directly targets a set of genes that are crucial for nucleotide metabolism, and this seems likely to represent one of the ways by which pRB influences the G1/S-phase transition and S-phase progression.

  9. Dehydromonocrotaline generates sequence-selective N-7 guanine alkylation and heat and alkali stable multiple fragment DNA crosslinks.

    OpenAIRE

    Pereira, T N; Webb, R I; Reilly, P E; Seawright, A. A.; Prakash, A S

    1998-01-01

    Monocrotaline is a pyrrolizidine alkaloid known to cause toxicity in humans and animals. Its mechanism of biological action is still unclear although DNA crosslinking has been suggested to a play a role in its activity. In this study we found that an active metabolite of monocrotaline, dehydromonocrotaline (DHM), alkylates guanines at the N7 position of DNA with a preference for 5'-GG and 5'-GA sequences. In addition, it generates piperidine- and heat-resistant multiple DNA crosslinks, as con...

  10. Load Concentration Factor Based Analytical Method for Optimal Placement of Multiple Distribution Generators for Loss Minimization and Voltage Profile Improvement

    OpenAIRE

    Mohsin Shahzad; Ishtiaq Ahmad; Wolfgang Gawlik; Peter Palensky

    2016-01-01

    This paper presents novel separate methods for finding optimal locations, sizes of multiple distributed generators (DGs) simultaneously and operational power factor in order to minimize power loss and improve the voltage profile in the distribution system. A load concentration factor (LCF) is introduced to select the optimal location(s) for DG placement. Exact loss formula based analytical expressions are derived for calculating the optimal sizes of any number of DGs simultaneously. Since nei...

  11. Performance of a direct steam generation solar thermal power plant for electricity production as a function of the solar multiple

    OpenAIRE

    Montes Pita, María José; Abánades Velasco, Alberto; Martínez-Val Peñalosa, Jose Maria

    2009-01-01

    This paper describes the influence of the solar multiple on the annual performance of parabolic trough solar thermal power plants with direct steam generation (DSG). The reference system selected is a 50 M We DSG power plant, with thermal storage and auxiliary natural gas-fired boiler. It is considered that both systems are necessary for an optimum coupling to the electricity grid. Although thermal storage is an opening issue for DSG technology, it gives an additional degree of freedom for pl...

  12. Photoexcited electron and hole dynamics in semiconductor quantum dots: phonon-induced relaxation, dephasing, multiple exciton generation and recombination.

    OpenAIRE

    Kim, Hyeon-Deuk; Prezhdo, Oleg V.

    2012-01-01

    Photoexcited dynamics of electrons and holes in semiconductor quantum dots (QD), including phonon-induced relaxation, multiple exciton generation, fission and recombination (MEG, MEF and MER), were simulated by combining ab initio time-dependent density functional theory and non-adiabatic molecular dynamics. These nonequilibrium phenomena govern the optical properties and photoexcited dynamics of QDs, determining the branching between electronic processes and thermal energy losses. Our approa...

  13. Generation and Characterization of Erythroid Cells from Human Embryonic Stem Cells and Induced Pluripotent Stem Cells: An Overview

    Directory of Open Access Journals (Sweden)

    Kai-Hsin Chang

    2011-01-01

    Full Text Available Because of the imbalance in the supply and demand of red blood cells (RBCs, especially for alloimmunized patients or patients with rare blood phenotypes, extensive research has been done to generate therapeutic quantities of mature RBCs from hematopoietic stem cells of various sources, such as bone marrow, peripheral blood, and cord blood. Since human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs can be maintained indefinitely in vitro, they represent potentially inexhaustible sources of donor-free RBCs. In contrast to other ex vivo stem-cell-derived cellular therapeutics, tumorigenesis is not a concern, as RBCs can be irradiated without marked adverse effects on in vivo function. Here, we provide a comprehensive review of the recent publications relevant to the generation and characterization of hESC- and iPSC-derived erythroid cells and discuss challenges to be met before the eventual realization of clinical usage of these cells.

  14. Human cytomegalovirus protects multiple myeloma cell line KM3 cells from apoptosis induced by growth factor withdrawal

    Institute of Scientific and Technical Information of China (English)

    魏国庆; 林茂芳; 黄河; 蔡真

    2004-01-01

    Background There is a higher rate of cytomegalovirus (CMV) reactivation in patients with multiple myeloma after an autologous stem cell transplantation, but no attention has been given thus far to a possible pathogenetic interplay between CMV and multiple myeloma. CMV can infect many kinds of cells, and CMV infection has been shown to inhibit apoptotic responses in several cell systems. In this study the authors investigated the alterations in apoptosis in the multiple myeloma cell line KM3 after infection with CMV and proposed a possible mechanism.Methods KM3 cells were infected with 100, 10, or 1 TCID50 of CMV and then cultured in serum-free RPMI 1640. An RT-PCR-based assay was used to detect mRNA expression of CMV-IE, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and IL-6 in CMV-infected and mock-infected cells. Flow cytometry was used to detect apoptotic cells. CMV particles and apoptotic cells were also examined with an electron microscope. Results CMV-infected KM3 cells clearly expressed immediate early (IE) antigen mRNA when compared to uninfected cells, and there were fewer apoptotic cells among cells treated with 100 or 10 TCID50 of CMV after culturing in serum-free RPMI 1640. CMV particles were observable in infected cells under an electron microscope. Expression of IL-6 mRNA increased after infection.Conclusion CMV can infect the multiple myeloma cell line KM3, inhibit the apoptotic response in these cells after apoptosis induction in serum-free culture, and increase the expression of IL-6 mRNA.

  15. Solution processing of next-generation nanocrystal solar cells

    Science.gov (United States)

    van Embden, J.; Chesman, A. S. R.; Duffy, N. W.; Della Gaspera, E.; Jasieniak, J. J.

    2013-12-01

    Next-generation solar cells will be fabricated from low-cost and earth abundant elements, using processes that are amenable to printing on a variety of light-weight substrates. The utilization of compositionally and structurally controlled colloidal nanocrystals as building blocks for such devices fulfills these criteria. Our recent efforts in developing kesterite Cu2ZnSnS4 (CZTS) nanocrystals, one of the most promising materials to emerge in this area, enable the deposition of CZTS thin-films directly from a variety of solution-processed methods. Nanocrystalline thin films possess poor electronic properties, which precludes their use in solar cell devices. In order to overcome this, thermal treatment steps under an atmosphere of vaporous selenium are applied to induce large scale crystallite growth and the production of selenized CZTSSe films. This process results in a highly photoactive p-type layer. The n-type cadmium sulfide layer is also deposited from solution using chemical bath deposition. We will discuss each of these accomplishments in detail, highlighting the significant challenges that need to be overcome in order to fabricate working CZTSSe thin film solar cells.

  16. Advances in understanding the cell types and approaches used for generating induced pluripotent stem cells.

    Science.gov (United States)

    Li, Jun; Song, Wei; Pan, Guangjin; Zhou, Jun

    2014-01-01

    Successfully reprogramming somatic cells to a pluripotent state generates induced pluripotent stem (iPS) cells (or iPSCs), which have extensive self-renewal capacity like embryonic stem cells (ESCs). iPSCs can also generate daughter cells that can further undergo differentiation into various lineages or terminally differentiate to reach their final functional state. The discovery of how to produce iPSCs opened a new field of stem cell research with both intellectual and therapeutic benefits. The huge potential implications of disease-specific or patient-specific iPSCs have impelled scientists to solve problems hindering their applications in clinical medicine, especially the issues of convenience and safety. To determine the range of tissue types amenable to reprogramming as well as their particular characteristics, cells from three embryonic germ layers have been assessed, and the advantages that some tissue origins have over fibroblast origins concerning efficiency and accessibility have been elucidated. To provide safe iPSCs in an efficient and convenient way, the delivery systems and combinations of inducing factors as well as the chemicals used to generate iPSCs have also been significantly improved in addition to the efforts on finding better donor cells. Currently, iPSCs can be generated without c-Myc and Klf4 oncogenes, and non-viral delivery integration-free chemically mediated reprogramming methods have been successfully employed with relatively satisfactory efficiency. This paper will review recent advances in iPS technology by highlighting tissue origin and generation of iPSCs. The obstacles that need to be overcome for clinical applications of iPSCs are also discussed.

  17. Multiple Modes of Communication between Neurons and Oligodendrocyte Precursor Cells

    NARCIS (Netherlands)

    Maldonado, Paloma P; Angulo, María Cecilia

    2015-01-01

    The surprising discovery of bona fide synapses between neurons and oligodendrocytes precursor cells (OPCs) 15 years ago placed these progenitors as real partners of neurons in the CNS. The role of these synapses has not been established yet, but a main hypothesis is that neuron-OPC synaptic activity

  18. A Progenitor Cell Expressing Transcription Factor RORγt Generates All Human Innate Lymphoid Cell Subsets.

    Science.gov (United States)

    Scoville, Steven D; Mundy-Bosse, Bethany L; Zhang, Michael H; Chen, Li; Zhang, Xiaoli; Keller, Karen A; Hughes, Tiffany; Chen, Luxi; Cheng, Stephanie; Bergin, Stephen M; Mao, Hsiaoyin C; McClory, Susan; Yu, Jianhua; Carson, William E; Caligiuri, Michael A; Freud, Aharon G

    2016-05-17

    The current model of murine innate lymphoid cell (ILC) development holds that mouse ILCs are derived downstream of the common lymphoid progenitor through lineage-restricted progenitors. However, corresponding lineage-restricted progenitors in humans have yet to be discovered. Here we identified a progenitor population in human secondary lymphoid tissues (SLTs) that expressed the transcription factor RORγt and was unique in its ability to generate all known ILC subsets, including natural killer (NK) cells, but not other leukocyte populations. In contrast to murine fate-mapping data, which indicate that only ILC3s express Rorγt, these human progenitor cells as well as human peripheral blood NK cells and all mature ILC populations expressed RORγt. Thus, all human ILCs can be generated through an RORγt(+) developmental pathway from a common progenitor in SLTs. These findings help establish the developmental signals and pathways involved in human ILC development.

  19. Biomimetic heterogeneous multiple ion channels: a honeycomb structure composite film generated by breath figures

    Science.gov (United States)

    Han, Keyu; Heng, Liping; Wen, Liping; Jiang, Lei

    2016-06-01

    We design a novel type of artificial multiple nanochannel system with remarkable ion rectification behavior via a facile breath figure (BF) method. Notably, even though the charge polarity in the channel wall reverses under different pH values, this nanofluidic device displays the same ionic rectification direction. Compared with traditional nanochannels, this composite multiple ion channel device can be more easily obtained and has directional ionic rectification advantages, which can be applied in many fields.We design a novel type of artificial multiple nanochannel system with remarkable ion rectification behavior via a facile breath figure (BF) method. Notably, even though the charge polarity in the channel wall reverses under different pH values, this nanofluidic device displays the same ionic rectification direction. Compared with traditional nanochannels, this composite multiple ion channel device can be more easily obtained and has directional ionic rectification advantages, which can be applied in many fields. Electronic supplementary information (ESI) available: Pore size distribution histograms of the AAO substrates; SEM images of the side view of pure AAO membranes and top view of the flat PI/AAO composite film; the current-time curves of the flat composite film; the current-voltage characteristics curves of pure AAO nanochannels with different mean pore diameters; CA of the two surfaces of the composite PI/AAO film, the structural formula of the polymer polyimide resin (PI), and solid surface zeta potential. See DOI: 10.1039/c6nr02506d

  20. WORKING FEATURES OF POWER SOURCE SYSTEMS – A MULTIPLE CURRENT PULSE GENERATOR

    Directory of Open Access Journals (Sweden)

    Shs.V. Argun

    2013-04-01

    Full Text Available An analysis of circuit designs as to connecting a magnetic pulse action tool to a power source has been carried out. Design features of a magnetic pulse installation control and monitoring system in a multiple current pulse mode have been revealed. The description of the control and monitoring system block diagrams has been presented.

  1. Sliding Mode Control of the Battery Bank for the Fuel Cell-based Distributed Generation System

    OpenAIRE

    Junsheng Jiao

    2013-01-01

    The dynamic models for the fuel cell power and the configuration of the fuel cell distributed generation system are shown in this paper. Due to nonlinear characteristics of fuel cell model, the output voltage of fuel cell varies greatly when the load changes. A novel interface is designed to provide a constant output voltage for charging of the battery bank of the fuel cell distributed generation. The thesis presents a sliding mode control design of PEMFC distributed generation system. A casc...

  2. Memory-Like CD8+ T Cells Generated during Homeostatic Proliferation Defer to Antigen-Experienced Memory Cells1

    OpenAIRE

    Cheung, Kitty P.; Yang, Edward; Goldrath, Ananda W

    2009-01-01

    Naive T cells proliferate in response to lymphopenia and acquire the phenotypic and functional qualities of memory T cells, providing enhanced protection against infection. How well memory-like T cells generated during lymphopenia-induced homeostatic proliferation (HP)-memory differentiate into secondary memory cells and compete with Ag-experienced true-memory cells is unknown. We found that CD8+ HP-memory T cells generated robust responses upon infection and produced a secondary memory popul...

  3. Intrinsic Connectivity of the Rat Subiculum: II. Properties of Synchronous Spontaneous Activity and a Demonstration of Multiple Generator Regions

    OpenAIRE

    HARRIS, ELANA; Stewart, Mark

    2001-01-01

    Brain structures that can generate epileptiform activity possess excitatory interconnections among principal cells and a subset of these neurons that can be spontaneously active (“pacemaker” cells). We describe electrophysiological evidence for excitatory interactions among rat subicular neurons. Subiculum was isolated from presubiculum, CA1, and entorhinal cortex in ventral horizontal slices. Nominally zero magnesium perfusate, picrotoxin (100 μM), or NMDA (20 μM) was used to induce spontane...

  4. Multiple Timescale Dispatch and Scheduling for Stochastic Reliability in Smart Grids with Wind Generation Integration

    OpenAIRE

    He, Miao; Murugesan, Sugumar; Zhang, Junshan

    2010-01-01

    Integrating volatile renewable energy resources into the bulk power grid is challenging, due to the reliability requirement that at each instant the load and generation in the system remain balanced. In this study, we tackle this challenge for smart grid with integrated wind generation, by leveraging multi-timescale dispatch and scheduling. Specifically, we consider smart grids with two classes of energy users - traditional energy users and opportunistic energy users (e.g., smart meters or sm...

  5. Enhanced generation of retinal progenitor cells from human retinal pigment epithelial cells induced by amniotic fluid

    Directory of Open Access Journals (Sweden)

    Sanie-Jahromi Fatemeh

    2012-04-01

    Full Text Available Abstract Background Retinal progenitor cells are a convenient source of cell replacement therapy in retinal degenerative disorders. The purpose of this study was to evaluate the expression patterns of the homeobox genes PAX6 and CHX10 (retinal progenitor markers during treatment of human retinal pigment epithelium (RPE cells with amniotic fluid (AF, RPE cells harvested from neonatal cadaver globes were cultured in a mixture of DMEM and Ham's F12 supplemented with 10% FBS. At different passages, cells were trypsinized and co-cultured with 30% AF obtained from normal fetuses of 1416 weeks gestational age. Results Compared to FBS-treated controls, AF-treated cultures exhibited special morphological changes in culture, including appearance of spheroid colonies, improved initial cell adhesion and ordered cell alignment. Cell proliferation assays indicated a remarkable increase in the proliferation rate of RPE cells cultivated in 30% AF-supplemented medium, compared with those grown in the absence of AF. Immunocytochemical analyses exhibited nuclear localization of retinal progenitor markers at a ratio of 33% and 27% for CHX10 and PAX6, respectively. This indicated a 3-fold increase in retinal progenitor markers in AF-treated cultures compared to FBS-treated controls. Real-time PCR data of retinal progenitor genes (PAX6, CHX10 and VSX-1 confirmed these results and demonstrated AF's capacity for promoting retinal progenitor cell generation. Conclusion Taken together, the results suggest that AF significantly promotes the rate of retinal progenitor cell generation, indicating that AF can be used as an enriched supplement for serum-free media used for the in vitro propagation of human progenitor cells.

  6. Generation of Human Lens Epithelial-Like Cells From Patient-Specific Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Li, Dan; Qiu, Xiaodi; Yang, Jin; Liu, Tianjin; Luo, Yi; Lu, Yi

    2016-12-01

    Cataractogenesis begins from the dynamic lens epithelial cells (LECs) and adjacent fiber cells. LECs derived from cell lines cannot maintain the crystalline expression as the primary LECs. The current study aimed to efficiently generate large numbers of human LECs from patient-specific induced pluripotent stem cells (iPSCs). Anterior lens capsules were collected from cataract surgery and were used to culture primary hLECs. iPSCs were induced from these primary hLECs by lentiviral transduction of Oct4, Sox2, Klf4, and c-Myc. Then, the generated iPSCs were re-differentiated into hLECs by the 3-step addition of defined factor combinations (Noggin, BMP4/7, bFGF, and EGF) modified from an established method. During the re-differentiation process, colonies of interest were isolated using a glass picking tool and cloning cylinders based on the colony morphology. After two steps of isolation, populations of LEC-like cells (LLCs) were generated and identified by the expression of lens marker genes by qPCR, western blot and immunofluorescence staining. The study introduced a modified protocol to isolate LLCs from iPSCs by defined factors in a short time frame. This technique could be useful for mechanistic studies of lens-related diseases. J. Cell. Physiol. 231: 2555-2562, 2016. © 2016 Wiley Periodicals, Inc. PMID:26991066

  7. Cell assemblies at multiple time scales with arbitrary lag distributions

    OpenAIRE

    Russo, Eleonora; Durstewitz, Daniel

    2016-01-01

    Hebb's idea of a cell assembly as the fundamental unit of neural information processing has dominated neuroscience like no other theoretical concept within the past 60 years. A range of different physiological phenomena, from precisely synchronized spiking to broadly simultaneous rate increases, has been subsumed under this term. Yet progress in this area is hampered by the lack of statistical tools that would enable to extract assemblies with arbitrary constellations of time lags, and at mul...

  8. Generation of embryonic stem cells from mouse adipose-tissue derived cells via somatic cell nuclear transfer.

    Science.gov (United States)

    Qin, Yiren; Qin, Jilong; Zhou, Chikai; Li, Jinsong; Gao, Wei-Qiang

    2015-01-01

    Somatic cells can be reprogrammed into embryonic stem cells (ESCs) by nuclear transfer (NT-ESCs), or into induced pluripotent stem cells (iPSCs) by the "Yamanaka method." However, recent studies have indicated that mouse and human iPSCs are prone to epigenetic and transcriptional aberrations, and that NT-ESCs correspond more closely to ESCs derived from in vitro fertilized embryos than iPSCs. In addition, the procedure of NT-ESCs does not involve gene modification. Demonstration of generation of NT-ESCs using an easily-accessible source of adult cell types would be very important. Adipose tissue is a source of readily accessible donor cells and can be isolated from both males and females at different ages. Here we report that NT-ESCs can be generated from adipose tissue-derived cells (ADCs). At morphological, mRNA and protein levels, these NT-ESCs show classic ESC colonies, exhibit alkaline phosphatase (AP) activity, and display normal diploid karyotypes. Importantly, these cells express pluripotent markers including Oct4, Sox2, Nanog and SSEA-1. Furthermore, they can differentiate in vivo into various types of cells from 3 germinal layers by teratoma formation assays. This study demonstrates for the first time that ESCs can be generated from the adipose tissue by somatic cell nuclear transfer (SCNT) and suggests that ADCs can be a new donor-cell type for potential therapeutic cloning.

  9. MULTIPLE EXCITON GENERATIONSOLAR CELLS USING CdSe QUANTUM DOTS

    Directory of Open Access Journals (Sweden)

    HAFTOM MESFIN GEBRESLASSIE,

    2011-03-01

    Full Text Available Experimental and Simulation works of Nano structured Solar Cells Using CdSe Quantum Dots have been analyzed and investigated. CdSe quantum dots have been synthesized from non coordinating and highboiling solvent Octadecene and a series of increasing CdSe particle sizes are produced. The synthesized CdSe quantum dots are highly examined under a Transmission Electron Microscope and four images ofdifferent sizes of CdSe quantum dots (5.8 nm, 6.4 nm, 7.0 nm and 7.7 nm have been obtained. A 1.1x1.1cm2 TiO2 electrode is prepared using indium tin oxide conducting glass and TiO2 nanoparticles. The CdSe quantum dot (5.8nm was adsorbed on TiO2 photoelectrode and used as sensitizer. In this paper work, a sandwich type cell configuration which is made up of TiO2 photoelectrode, graphite coated counter electrode, an electrolyte of iodine and potassium iodide have been used. This sandwich type cell has been exposed to sun light and we have achieved 0.32 V and 0.2 mA

  10. Electricity generation from the mud by using microbial fuel cell

    Directory of Open Access Journals (Sweden)

    Idris Sitinoor Adeib

    2016-01-01

    Full Text Available Microbial fuel cells (MFCs is a bio-electrochemical device that harnesses the power of respiring microbes to convert organic substrates directly into electrical energy. This is achieved when bacteria transfer electrons to an electrode rather than directly to an electron acceptor. Their technical feasibility has recently been proven and there is great enthusiasm in the scientific community that MFCs could provide a source of “green electricity”. Microbial fuel cells work by allowing bacteria to do what they do best, oxidize and reduce organic molecules. Bacterial respiration is basically one big redox reaction in which electrons are being moved around. The objective is to generate electricity throughout the biochemical process using chemical waste basically sludge, via microbial fuel cells. The methodology includes collecting sludge from different locations, set up microbial fuel cells with the aid of salt bridge and observing the results in voltage measurement. The microbial fuel cells consist of two chambers, iron electrodes, copper wire, air pump (to increase the efficiency of electron transfer, water, sludge and salt bridge. After several observations, it is seen that this MFC can achieve up until 202 milivolts (0.202volts with the presence of air pump. It is proven through the experiments that sludge from different locations gives different results in term of the voltage measurement. This is basically because in different locations of sludge contain different type and amount of nutrients to provide the growth of bacteria. Apart from that, salt bridge also play an important role in order to transport the proton from cathode to anode. A longer salt bridge will give a higher voltage compared to a short salt bridge. On the other hand, the limitations that this experiment facing is the voltage that being produced did not last long as the bacteria activity slows down gradually and the voltage produced are not really great in amount. Lastly to

  11. Next Generation Bipolar Plates for Automotive PEM Fuel Cells

    Energy Technology Data Exchange (ETDEWEB)

    Adrianowycz, Orest; Norley, Julian; Stuart, David J; Flaherty, David; Wayne, Ryan; ; Williams, Warren; Tietze, Roger; Nguyen, Yen-Loan H; Zawodzinski, Tom; Pietrasz, Patrick

    2010-04-15

    The results of a successful U.S. Department of Energy (DoE) funded two-year $2.9 MM program lead by GrafTech International Inc. (GrafTech) are reported and summarized. The program goal was to develop the next generation of high temperature proton exchange membrane (PEM) fuel cell bipolar plates for use in transportation fuel cell applications operating at temperatures up to 120 °C. The bipolar plate composite developed during the program is based on GrafTech’s GRAFCELL resin impregnated flexible graphite technology and makes use of a high temperature Huntsman Advanced Materials resin system which extends the upper use temperature of the composite to the DoE target. High temperature performance of the new composite is achieved with the added benefit of improvements in strength, modulus, and dimensional stability over the incumbent resin systems. Other physical properties, including thermal and electrical conductivity of the new composite are identical to or not adversely affected by the new resin system. Using the new bipolar plate composite system, machined plates were fabricated and tested in high temperature single-cell fuel cells operating at 120 °C for over 1100 hours by Case Western Reserve University. Final verification of performance was done on embossed full-size plates which were fabricated and glued into bipolar plates by GrafTech. Stack testing was done on a 10-cell full-sized stack under a simulated drive cycle protocol by Ballard Power Systems. Freeze-thaw performance was conducted by Ballard on a separate 5-cell stack and shown to be within specification. A third stack was assembled and shipped to Argonne National Laboratory for independent performance verification. Manufacturing cost estimate for the production of the new bipolar plate composite at current and high volume production scenarios was performed by Directed Technologies Inc. (DTI). The production cost estimates were consistent with previous DoE cost estimates performed by DTI for the

  12. A novel in vitro multiple-stress dormancy model for Mycobacterium tuberculosis generates a lipid-loaded, drug-tolerant, dormant pathogen.

    Directory of Open Access Journals (Sweden)

    Chirajyoti Deb

    Full Text Available BACKGROUND: Mycobacterium tuberculosis (Mtb becomes dormant and phenotypically drug resistant when it encounters multiple stresses within the host. Inability of currently available drugs to kill latent Mtb is a major impediment to curing and possibly eradicating tuberculosis (TB. Most in vitro dormancy models, using single stress factors, fail to generate a truly dormant Mtb population. An in vitro model that generates truly dormant Mtb cells is needed to elucidate the metabolic requirements that allow Mtb to successfully go through dormancy, identify new drug targets, and to screen drug candidates to discover novel drugs that can kill dormant pathogen. METHODOLOGY/PRINCIPAL FINDINGS: We developed a novel in vitro multiple-stress dormancy model for Mtb by applying combined stresses of low oxygen (5%, high CO(2 (10%, low nutrient (10% Dubos medium and acidic pH (5.0, conditions Mtb is thought to encounter in the host. Under this condition, Mtb stopped replicating, lost acid-fastness, accumulated triacylglycerol (TG and wax ester (WE, and concomitantly acquired phenotypic antibiotic-resistance. Putative neutral lipid biosynthetic genes were up-regulated. These genes may serve as potential targets for new antilatency drugs. The triacylglycerol synthase1 (tgs1 deletion mutant, with impaired ability to accumulate TG, exhibited a lesser degree of antibiotic tolerance and complementation restored antibiotic tolerance. Transcriptome analysis with microarray revealed the achievement of dormant state showing repression of energy generation, transcription and translation machineries and induction of stress-responsive genes. We adapted this model for drug screening using the Alamar Blue dye to quantify the antibiotic tolerant dormant cells. CONCLUSIONS/SIGNIFICANCE: The new in vitro multiple stress dormancy model efficiently generates Mtb cells meeting all criteria of dormancy, and this method is adaptable to high-throughput screening for drugs that can

  13. Autophagy counteracts apoptosis in human multiple myeloma cells exposed to oridonin in vitro via regulating intracellular ROS and SIRT1

    Institute of Scientific and Technical Information of China (English)

    Rong ZENG; Yan CHEN; Shuai ZHAO; Guo-hui CUI

    2012-01-01

    To explore the mechanisms underlying the oridonin-induced apoptosis and autophagy in human multiple myeloma cells in vitro.Methods:Human multiple myeloma RPMI8266 cells were used.The cell viability was assessed using MTT assay.Morphological changes of apoptosis and autophagy were observed under transmission electron microscope.TUNEL and annexin V-FITC/PI dual staining assays were used to measure apoptosis.Autophagy was analyzed using Western blot analysis and immunofluorescence staining with a QDs605 nm-Anti-LC3 fluorescent probe.Intracellular ROS was estimated with flow cytometry using DCFH-DA fluorescent probe.Protein levels of active caspase 3,Beclin 1 and SIRT1 were determined with Western blot analysis.Results:Exposure to oridonin (1-64 μmol/L) inhibited the proliferation of RPMI8266 cells in a concentration-dependent manner with an IC50 value of 6.74 μmol/L.Exposure to oridonin (7 μmol/L) simultaneously induced caspase 3-mediated apoptosis and Beclin 1-dependent autophagy of RPMI8266 cells.Both the apoptosis and autophagy were time-dependent,and apoptosis was the main effector pathway of cell death.Exposure to oridonin (7 μmol/L) increased intracellular ROS and reduced SIRT1 nuclear protein in a time-dependent manner.The blockade of intracellular generation of ROS by NAC (5 mmol/L) abrogated apoptosis,autophagy and the decrease of SIRT1 in the cells exposed to oridonin (7 μmol/L).The inhibition of autophagy by 3-MA (5 mmol/L) sensitized the cells to oridonin-induced apoptosis,which was accompanied by increased intracellular ROS and decreased SlRT1.Conclusion:Oridonin simultaneously induces apoptosis and autophagy of human multiple myeloma RPMI8266 cells via regulation of intracellular ROS generation and SIRT1 nuclear protein.The cytotoxicity of oridonin is mainly mediated through the apoptotic pathway,whereas the autophagy protects the cells from apoptosis.

  14. Multiple Myeloma

    Science.gov (United States)

    Multiple myeloma is a cancer that begins in plasma cells, a type of white blood cell. These cells ... bones. No one knows the exact causes of multiple myeloma, but it is more common in older people ...

  15. A novel Multiple-Marker Method for the Early Diagnosis of Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Jutta Ries

    2009-01-01

    Full Text Available Objective: Melanoma associated antigens-A (MAGE-A expression is highly specific to cancer cells. Thus, they can be the most suitable targets for the diagnosis of malignancy. The aim of this study was to evaluate the sensitivity of multiple MAGE-A expression analysis for the diagnosis of oral squamous cell carcinoma (OSCC.

  16. Power generation from furfural using the microbial fuel cell

    Science.gov (United States)

    Luo, Yong; Liu, Guangli; Zhang, Renduo; Zhang, Cuiping

    Furfural is a typical inhibitor in the ethanol fermentation process using lignocellulosic hydrolysates as raw materials. In the literature, no report has shown that furfural can be utilized as the fuel to produce electricity in the microbial fuel cell (MFC), a device that uses microbes to convert organic compounds to generate electricity. In this study, we demonstrated that electricity was successfully generated using furfural as the sole fuel in both the ferricyanide-cathode MFC and the air-cathode MFC. In the ferricyanide-cathode MFC, the maximum power densities reached 45.4, 81.4, and 103 W m -3, respectively, when 1000 mg L -1 glucose, a mixture of 200 mg L -1 glucose and 5 mM furfural, and 6.68 mM furfural were used as the fuels in the anode solution. The corresponding Coulombic efficiencies (CE) were 4.0, 7.1, and 10.2% for the three treatments, respectively. For pure furfural as the fuel, the removal efficiency of furfural reached up to 95% within 12 h. In the air-cathode MFC using 6.68 mM furfural as the fuel, the maximum values of power density and CE were 361 mW m -2 (18 W m -3) and 30.3%, respectively, and the COD removal was about 68% at the end of the experiment (about 30 h). Increase in furfural concentrations from 6.68 to 20 mM resulted in increase in the maximum power densities from 361 to 368 mW m -2, and decrease in CEs from 30.3 to 20.6%. These results indicated that some toxic and biorefractory organics such as furfural might still be suitable resources for electricity generation using the MFC technology.

  17. Time Dependent Study of Multiple Exciton Generation in Nanocrystal Quantum Dots

    Science.gov (United States)

    Damtie, Fikeraddis A.; Wacker, Andreas

    2016-03-01

    We study the exciton dynamics in an optically excited nanocrystal quantum dot. Multiple exciton formation is more efficient in nanocrystal quantum dots compared to bulk semiconductors due to enhanced Coulomb interactions and the absence of conservation of momentum. The formation of multiple excitons is dependent on different excitation parameters and the dissipation. We study this process within a Lindblad quantum rate equation using the full many-particle states. We optically excite the system by creating a single high energy exciton ESX in resonance to a double exciton EDX. With Coulomb electron-electron interaction, the population can be transferred from the single exciton to the double exciton state by impact ionisation (inverse Auger process). The ratio between the recombination processes and the absorbed photons provide the yield of the structure. We observe a quantum yield of comparable value to experiment assuming typical experimental conditions for a 4 nm PbS quantum dot.

  18. Multiple junction II-VI compound photoelectrochemical cells

    Science.gov (United States)

    Russak, Michael A.

    1986-12-01

    The application of concepts used in producing tandem solid state photovoltaic devices to photoelectrochemical cells has resulted in improved spectral response and photovoltaic output. As in solid state devices, the key to achieving good photovoltaic performance is optimization of the semiconductor properties in each part of the tandem arrangement. This has been done for the thin film CdS/CdSe/sulfide-polysulfide system with an improvement of over 15 percent in conversion efficiency being obtained. Preliminary results showing significant current enhancement by the addition of a CdSe backwall electrode to the CdTe/selenide-polyselenide system are also reported.

  19. Effect of computer-generated prompts on physician prescribing of multiple daily doses.

    Science.gov (United States)

    Atkinson, V; Andrews, J D

    1987-06-01

    Cost containment of health care costs and computerization of pharmacy services are two trends that have become evident in recent years. The work described here was an attempt to reduce the prescribing of multiple daily doses of medications that could be prescribed once or twice daily by utilizing a pharmacy computer system. Ten drugs were identified as being prescribed more than 30% of the time in more frequent dosing schedules than recommended in the literature. Five of the drugs were randomly assigned to an experimental group and five to a control group. The computer system included a reminder with all experimental drug group orders for drugs effective given once or twice daily for maintenance therapy. This reminder was printed on both the physician's active medication profile and the nurse's medication administration record. The control period was designated as being the four month period prior to the initiation of the study. The experimental period was identified as the following four months where reminders were included with the drugs. No information concerning the study was circulated to the physicians or nursing staff. The results revealed no trend of fewer orders for multiple doses in the experimental group. In fact, all drugs in both the experimental and control groups showed random fluctuations in the number of orders for multiple doses. Possible reasons for the failure of this project include the impact of the reminders on the physicians, the timing of the study, and the medical condition of the patients. PMID:10282583

  20. HIGH EFFICIENCY, LOW EMISSIONS, SOLID OXIDE FUEL CELL SYSTEMS FOR MULTIPLE APPLICATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Sara Ward; Michael A. Petrik

    2004-07-28

    Technology Management Inc. (TMI), teamed with the Ohio Office of Energy Efficiency and Renewable Energy, has engineered, constructed, and demonstrated a stationary, low power, multi-module solid oxide fuel cell (SOFC) prototype system operating on propane and natural gas. Under Phase I, TMI successfully operated two systems in parallel, in conjunction with a single DC-AC inverter and battery bus, and produced net AC electricity. Phase II testing expanded to include alternative and renewable fuels typically available in rural regions of Ohio. The commercial system is expected to have ultra-low pollution, high efficiency, and low noise. The TMI SOFC uses a solid ceramic electrolyte operating at high temperature (800-1000 C) which electrochemically converts gaseous fuels (hydrogen or mixed gases) and oxygen into electricity. The TMI system design oxidizes fuel primarily via electrochemical reactions and uses no burners (which pollute and consume fuel)--resulting in extremely clean exhaust. The use of proprietary sulfur tolerant materials developed by TMI allows system operation without additional fuel pre-processing or sulfur removal. Further, the combination of high operating temperatures and solid state operation increases the potential for higher reliability and efficiencies compared to other types of fuel cells. Applications for the TMI SOFC system cover a wide range of transportation, building, industrial, and military market sectors. A generic technology, fuel cells have the potential to be embodied into multiple products specific to Department of Energy (DOE) Office of Energy Efficiency and Renewable Energy (EERE) program areas including: Fuel Cells and Microturbines, School Buildings, Transportation, and Bioenergy. This program focused on low power stationary applications using a multi-module system operating on a range of common fuels. By producing clean electricity more efficiently (thus using less fuel), fuel cells have the triple effect of cleaning up the

  1. Generation of functional CD8+ T Cells by human dendritic cells expressing glypican-3 epitopes

    Directory of Open Access Journals (Sweden)

    Farzaneh Farzin

    2010-05-01

    Full Text Available Abstract Background Glypican 3 (GPC-3 is an oncofoetal protein that is expressed in most hepatocellular carcinomas (HCC. Since it is a potential target for T cell immunotherapy, we investigated the generation of functional, GPC-3 specific T cells from peripheral blood mononuclear cells (PBMC. Methods Dendritic cells (DC were derived from adherent PBMC cultured at 37°C for 7 days in X-Vivo, 1% autologous plasma, and 800 u/ml GM-CSF plus 500 u/ml IL-4. Immature DC were transfected with 20 μg of in vitro synthesised GPC-3 mRNA by electroporation using the Easy-ject plus system (Equibio, UK (300 V, 150 μF and 4 ms pulse time, or pulsed with peptide, and subsequently matured with lipopolysaccharide (LPS. Six predicted GPC-3 peptide epitopes were synthesized using standard f-moc technology and tested for their binding affinity to HLA-A2.1 molecules using the cell line T2. Results DC transfected with GPC-3 mRNA but not control DC demonstrated strong intracellular staining for GPC-3 and in vitro generated interferon-gamma expressing T cells from autologous PBMC harvested from normal subjects. One peptide, GPC-3522-530 FLAELAYDL, fulfilled our criteria as a naturally processed, HLA-A2-restricted cytotoxic T lymphocyte (CTL epitope: i it showed high affinity binding to HLA-A2, in T2 cell binding assay; ii it was generated by the MHC class I processing pathway in DC transfected with GPC-3 mRNA, and iii HLA-A2 positive DC loaded with the peptide stimulated proliferation in autologous T cells and generated CTL that lysed HLA-A2 and GPC-3 positive target cells. Conclusions These findings demonstrate that electroporation of GPC-3 mRNA is an efficient method to load human monocyte-derived DC with antigen because in vitro they generated GPC-3-reactive T cells that were functional, as shown by interferon-gamma production. Furthermore, this study identified a novel naturally processed, HLA-A2-restricted CTL epitope, GPC-3522-530 FLAELAYDL, which can be used to

  2. Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Pratheeshkumar, Poyil; Son, Young-Ok; Divya, Sasidharan Padmaja; Roy, Ram Vinod; Hitron, John Andrew; Wang, Lei [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Kim, Donghern; Dai, Jin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Asha, Padmaja [National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Cochin (India); Zhang, Zhuo [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Wang, Yitao [State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau (China); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States)

    2014-12-01

    Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Inhibition of metal induced carcinogenesis by a dietary antioxidant is a novel approach. Luteolin, a natural dietary flavonoid found in fruits and vegetables, possesses potent antioxidant and anti-inflammatory activity. We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5 μM) showed a drastic increase in ROS generation, NADPH oxidase (NOX) activation, lipid peroxidation, and glutathione depletion, which were significantly inhibited by the treatment with luteolin in a dose dependent manner. Treatment with luteolin decreased AP-1, HIF-1α, COX-2, and iNOS promoter activity induced by Cr(VI) in BEAS-2B cells. In addition, luteolin protected BEAS-2B cells from malignant transformation induced by chronic Cr(VI) exposure. Moreover, luteolin also inhibited the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and VEGF in chronic Cr(VI) exposed BEAS-2B cells. Western blot analysis showed that luteolin inhibited multiple gene products linked to survival (Akt, Fak, Bcl-2, Bcl-xL), inflammation (MAPK, NF-κB, COX-2, STAT-3, iNOS, TNF-α) and angiogenesis (HIF-1α, VEGF, MMP-9) in chronic Cr(VI) exposed BEAS-2B cells. Nude mice injected with BEAS-2B cells chronically exposed to Cr(VI) in the presence of luteolin showed reduced tumor incidence compared to Cr(VI) alone treated group. Overexpression of catalase (CAT) or SOD2, eliminated Cr(VI)-induced malignant transformation. Overall, our results indicate that luteolin protects BEAS-2B cells from Cr(VI)-induced carcinogenesis by scavenging ROS and modulating multiple cell signaling mechanisms that are linked to ROS. Luteolin, therefore, serves as a potential chemopreventive agent against Cr(VI)-induced carcinogenesis. - Highlights: • Luteolin inhibited Cr(VI)-induced oxidative stress. • Luteolin inhibited chronic Cr(VI)-induced malignant transformation.

  3. Tuning cell migration: contractility as an integrator of intracellular signals from multiple cues.

    Science.gov (United States)

    Bordeleau, Francois; Reinhart-King, Cynthia A

    2016-01-01

    There has been immense progress in our understanding of the factors driving cell migration in both two-dimensional and three-dimensional microenvironments over the years. However, it is becoming increasingly evident that even though most cells share many of the same signaling molecules, they rarely respond in the same way to migration cues. To add to the complexity, cells are generally exposed to multiple cues simultaneously, in the form of growth factors and/or physical cues from the matrix. Understanding the mechanisms that modulate the intracellular signals triggered by multiple cues remains a challenge. Here, we will focus on the molecular mechanism involved in modulating cell migration, with a specific focus on how cell contractility can mediate the crosstalk between signaling initiated at cell-matrix adhesions and growth factor receptors. PMID:27508074

  4. Multiple loci are associated with white blood cell phenotypes.

    Directory of Open Access Journals (Sweden)

    Michael A Nalls

    2011-06-01

    Full Text Available White blood cell (WBC count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2, including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across

  5. Cytotoxicity of graphene oxide and graphene oxide loaded with doxorubicin on human multiple myeloma cells

    Directory of Open Access Journals (Sweden)

    Wu S

    2014-03-01

    Full Text Available Shaoling Wu,1 Xindong Zhao,2 Zhongguang Cui,1 Chunting Zhao,1 Yuzhen Wang,1 Li Du,1 Yanhui Li3 1Department of Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, People's Republic of China; 2Department of Hematology, Medical College of Qingdao University, Qingdao, Shandong, People's Republic of China; 3Laboratory of Fiber Materials and Modern Textile, The Growing Base for State Key Laboratory, Qingdao University, Qingdao, Shandong, People's Republic of China Abstract: The purpose of this study was to evaluate the cytotoxicity of human multiple myeloma cells (RPMI-8226 treated with graphene oxide (GO, doxorubicin (DOX, and GO loaded with DOX (GO/DOX. Cell viability was determined using the Cell Counting Kit-8 assay and analyzing the cell cycle and cell apoptosis. Cells treated with GO, GO/DOX, and pure DOX for 24 hours showed a decrease in proliferation. GO/DOX significantly inhibited cell proliferation as compared with pure DOX (P<0.01. When the effects of GO were removed, there was no observed difference between GO/DOX and pure DOX (P>0.05. Flow cytometry analysis of untreated and GO-, DOX-, and GO/DOX-treated cells found no significant differences in the G0/G1 phase (P>0.05, while significant differences were observed in the total apoptotic rates (P<0.05. No significant differences existed in the total apoptotic rates of GO-treated and untreated cells (P>0.05. These findings suggest that GO caused low cytotoxicity and did not induce cell apoptosis or change the cell cycle in multiple myeloma cells. Moreover, GO did not affect the antitumor activity of DOX. In conclusion, GO would be suitable as an anticancer drug nanocarrier and used to treat hematological malignancies. Keywords: graphene oxide, doxorubicin, human multiple myeloma cell, CCK-8, cell cycle, cell apoptosis

  6. Peripheral Blood Mononuclear Cell Membrane Fluidity and Disease Outcome in Patients with Multiple Sclerosis

    OpenAIRE

    Gloudina M Hon; Hassan, Mogamat S.; van Rensburg, Susan J.; Abel, Stefan; Erasmus, Rajiv T; Matsha, Tandi

    2011-01-01

    Immune cell membrane lipids are important determinants of membrane fluidity, eicosanoid production and phagocytosis and fatty acid metabolic abnormalities have been reported in immune cells from patients with multiple sclerosis. The aim of this study was to investigate the relationship between peripheral blood mononuclear cell membrane fluidity, permeability status, and disease outcome as measured by the Kurtzke expanded disability status scale. Phospholipids, fatty acids and cholesterol comp...

  7. Generation of multiple optical frequencies referenced to a frequency comb for precision free-space frequency transfer

    Science.gov (United States)

    Chun, Byung Jae; Kang, Hyun Jay; Kim, Young-Jin; Kim, Seung-Woo

    2016-03-01

    Generating multiple optical frequencies referenced to the frequency standard is an important task in optical clock dissemination and optical communication. An apparatus for frequency-comb-referenced generation of multiple optical frequencies is demonstrated for high-precision free-space transfer of multiple optical frequencies. The relative linewidth and frequency instability at each channel corresponds to sub-1 Hz and 1.06×10-15 at 10 s averaging time, respectively. During the free-space transfer, the refractive index change of transmission media caused by atmospheric turbulences induces phase and frequency noise on optical frequencies. These phase and frequency noise causes induced linewidth broadening and frequency shift in optical frequencies which can disturb the accurate frequency transfer. The proposed feedback loop with acousto-optic modulator can monitor and compensate phase/frequency noise on optical frequencies. As a result, a frequency-comb-referenced single optical mode is compensated with a high signal to noise ratio (SNR) of 80 dB. By sharing the same optical paths, this feedback loop is confirmed to be successfully transferred to the neighboring wavelength channels (a 100 GHz spaced channel). This result confirms our proposed system can transfer optical frequencies to the remote site in free-space without performance degradation.

  8. Multiple knickpoints in an alluvial river generated by a single instantaneous drop in base level: experimental investigation

    Science.gov (United States)

    Cantelli, A.; Muto, T.

    2014-05-01

    Knickpoints often form in bedrock rivers in response to base-level lowering. These knickpoints can migrate upstream without dissipating. In the case of alluvial rivers, an impulsive lowering of base level due to, for example, a fault associated with an earthquake or dam removal commonly produces smooth, upstream-progressing degradation; the knickpoint associated with suddenly lowered base level quickly dissipates. Here, however, we use experiments to demonstrate that under conditions of Froude-supercritical flow over an alluvial bed, an instantaneous drop in base level can lead to the formation of upstream-migrating knickpoints that do not dissipate. The base-level fall can generate a single knickpoint, or multiple knickpoints. Multiple knickpoints take the form of cyclic steps, that is, trains of upstream-migrating bedforms, each bounded by a hydraulic jump upstream and downstream. In our experiments, trains of knickpoints were transient, eventually migrating out of the alluvial reach as the bed evolved to a new equilibrium state regulated with lowered base level. Thus the allogenic perturbation of base-level fall can trigger the autogenic generation of multiple knickpoints which are sustained until the alluvial reach recovers a graded state.

  9. Structural templating of multiple polycrystalline layers in organic photovoltaic cells

    Energy Technology Data Exchange (ETDEWEB)

    Lassiter, Brian E; Lunt, Richard R; Renshaw, Kyle; Forrest, Stephen R.

    2010-09-01

    We demonstrate that organic photovoltaic cell performance is influenced by changes in the crystalline orientation of composite layer structures. A 1.5 nm thick self-organized, polycrystalline template layer of 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) orients subsequently deposited layers of a diindenoperylene exciton blocking layer, and the donor, copper phthalocyanine (CuPc). Control over the crystalline orientation of the CuPc leads to changes in its frontier energy levels, absorption coefficient, and surface morphology, resulting in an increase of power conversion efficiency at 1 sun from 1.42 ± 0.04% to 2.19 ± 0.05% for a planar heterojunction and from 1.89 ± 0.05% to 2.49 ± 0.03% for a planar-mixed heterojunction.

  10. Structural templating of multiple polycrystalline layers in organic photovoltaic cells.

    Science.gov (United States)

    Lassiter, Brian E; Lunt, Richard R; Renshaw, C Kyle; Forrest, Stephen R

    2010-09-13

    We demonstrate that organic photovoltaic cell performance is influenced by changes in the crystalline orientation of composite layer structures. A 1.5 nm thick self-organized, polycrystalline template layer of 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) orients subsequently deposited layers of a diindenoperylene exciton blocking layer, and the donor, copper phthalocyanine (CuPc). Control over the crystalline orientation of the CuPc leads to changes in its frontier energy levels, absorption coefficient, and surface morphology, resulting in an increase of power conversion efficiency at 1 sun from 1.42 ± 0.04% to 2.19 ± 0.05% for a planar heterojunction and from 1.89 ± 0.05% to 2.49 ± 0.03% for a planar-mixed heterojunction. PMID:21165074

  11. Germ Cell Cancer and Multiple Relapses: Toxicity and Survival

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Kier, Maria G.G.; Mortensen, Mette S.;

    2015-01-01

    Purpose: A small number of patients with germ cell cancer (GCC) receive more than one line of treatment for disseminated disease. The purpose of this study was to evaluate late toxicity and survival in an unselected cohort of patients who experienced relapse after receiving first-line treatment...... for disseminated disease. Methods: From the Danish Testicular Cancer database, we identified all patients who received more than one line of treatment for disseminated disease. Information about late toxicity and mortality was obtained by means of linkage to national registers. Prognostic factors for relapse...... chorionic gonadotropin as independent factors. We identified increasing age as a possible new prognostic factor for treatment failure after second-line treatment (HR, 1.2 per 10 years; 95% CI, 1.2 to 15). Conclusion: Patients with GCC who survive after more than one line of treatment for disseminated...

  12. The Correlation Function of Multiple Dependent Poisson Processes Generated by the Alternating Renewal Process Method

    CERN Document Server

    Johnson, Don H

    2008-01-01

    We derive conditions under which alternating renewal processes can be used to construct correlated Poisson processes. The pairwise correlation function is also derived, showing that the resulting correlations can be negative. The technique and the analysis can be extended to the generation of two or more dependent renewal processes.

  13. Deficient Fas expression by CD4+ CCR5+ T cells in multiple sclerosis

    DEFF Research Database (Denmark)

    Julià, Eva; Montalban, Xavier; Al-Zayat, Hammad;

    2006-01-01

    OBJECTIVE: To evaluate whether T cells expressing CCR5 and CXCR3 from multiple sclerosis (MS) patients are more resistant to apoptosis. METHODS: Expression of CD69, TNF-R1, Fas, FasL, bcl-2, and bax was investigated in 41 MS patients and 12 healthy controls by flow cytometry in CD4+ and CD8+ T...... cells expressing CCR5 and CXCR3. RESULTS: In MS patients, the percentage of CD69 was increased and Fas expression decreased in CD4+ CCR5+ T cells. INTERPRETATION: The lower Fas expression in activated CD4+ CCR5+ T cells might contribute to disease pathogenesis by prolonging cell survival and favoring...

  14. Multiple-cylindrical Electrode System for Rotational Electric Field Generation in Particle Rotation Applications

    Directory of Open Access Journals (Sweden)

    Prateek Benhal

    2015-07-01

    Full Text Available Lab-on-a-chip micro-devices utilizing electric field-mediated particle movement provide advantages over current cell rotation techniques due to the flexibility in configuring micro-electrodes. Recent technological advances in micro-milling, three-dimensional (3D printing and photolithography have facilitated fabrication of complex micro-electrode shapes. Using the finite-element method to simulate and optimize electric field induced particle movement systems can save time and cost by simplifying the analysis of electric fields within complex 3D structures. Here we investigated different 3D electrode structures to obtain and analyse rotational electric field vectors. Finite-element analysis was conducted by an electric current stationary solver based on charge relaxation theory. High-resolution data were obtained for three-, four-, six- and eight-cylindrical electrode arrangements to characterize the rotational fields. The results show that increasing the number of electrodes within a fixed circular boundary provides larger regions of constant amplitude rotational electric field. This is a very important finding in practice, as larger rotational regions with constant electric field amplitude make placement of cells into these regions, where cell rotation occurs, a simple task – enhancing flexibility in cell manipulation. Rotation of biological particles over the extended region would be useful for biotechnology applications which require guiding cells to a desired location, such as automation of nuclear transfer cloning.

  15. Multiplication of human NHIK 3025 cells exposed to porphyrins in combination with light.

    OpenAIRE

    Christensen, T.

    1981-01-01

    Cells from the established line NHIK 3025 were exposed to haematoporphyrin derivative and light. After this photodynamic treatment the first interphase of surviving cells was prolonged. Furthermore, a pronounced effect on the progression through the first mitosis was observed. Mainly the duration of metaphase was increased. Some of the cells were irreversibly arrested in mitosis and the cells that were able to complete mitosis after treatment multiplied in the subsequent generations at the sa...

  16. SIRT1 deacetylates RORγt and enhances Th17 cell generation

    OpenAIRE

    Lim, Hyung W; Kang, Seung Goo; Ryu, Jae Kyu; Schilling, Birgit; Fei, Mingjian; Lee, Intelly S; Kehasse, Amanuel; Shirakawa, Kotaro; Yokoyama, Masaru; Schnölzer, Martina; Kasler, Herbert G; Kwon, Hye-Sook; Bradford W Gibson; Sato, Hironori; Akassoglou, Katerina

    2015-01-01

    The balance of effector and regulatory T cell function, dependent on multiple signals and epigenetic regulators, is critical to immune self-tolerance. Dysregulation of T helper 17 (Th17) effector cells is associated with multiple autoimmune diseases, including multiple sclerosis. Here, we report that Sirtuin 1 (SIRT1), a protein deacetylase previously reported to have an antiinflammatory function, in fact promotes autoimmunity by deacetylating RORγt, the signature transcription factor of Th17...

  17. Automatic selection of informative sentences: The sentences that can generate multiple choice questions

    Directory of Open Access Journals (Sweden)

    Mukta Majumder

    2014-12-01

    Full Text Available Traditional education cannot meet the expectation and requirement of a Smart City; it require more advance forms like active learning, ICT education etc. Multiple choice questions (MCQs play an important role in educational assessment and active learning which has a key role in Smart City education. MCQs are effective to assess the understanding of well-defined concepts. A fraction of all the sentences of a text contain well-defined concepts or information that can be asked as a MCQ. These informative sentences are required to be identified first for preparing multiple choice questions manually or automatically. In this paper we propose a technique for automatic identification of such informative sentences that can act as the basis of MCQ. The technique is based on parse structure similarity. A reference set of parse structures is compiled with the help of existing MCQs. The parse structure of a new sentence is compared with the reference structures and if similarity is found then the sentence is considered as a potential candidate. Next a rule-based post-processing module works on these potential candidates to select the final set of informative sentences. The proposed approach is tested in sports domain, where many MCQs are easily available for preparing the reference set of structures. The quality of the system selected sentences is evaluated manually. The experimental result shows that the proposed technique is quite promising.

  18. Effect of secondary convective cells on turbulence intensity profiles, flow generation, and transport

    Energy Technology Data Exchange (ETDEWEB)

    Yi, S.; Kwon, J. M.; Rhee, T. [National Fusion Research Institute, Eoeun-dong, Yuseong-gu, Daejeon 305-333 (Korea, Republic of); Diamond, P. H. [National Fusion Research Institute, Eoeun-dong, Yuseong-gu, Daejeon 305-333 (Korea, Republic of); Center for Astrophysics and Space Sciences and Department of Physics, University of California San Diego, La Jolla, California 92093-0429 (United States)

    2012-11-15

    This paper reports the results of gyrokinetic simulation studies of ion temperature gradient driven turbulence which investigate the role of non-resonant modes in turbulence spreading, turbulence regulation, and self-generated plasma rotation. Non-resonant modes, which are those without a rational surface within the simulation domain, are identified as nonlinearly driven, radially extended convective cells. Even though the amplitudes of such convective cells are much smaller than that of the resonant, localized turbulence eddies, we find from bicoherence analysis that the mode-mode interactions in the presence of such convective cells increase the efficiency of turbulence spreading associated with nonlocality phenomena. Artificial suppression of the convective cells shows that turbulence spreading is reduced, and that the turbulence intensity profile is more localized. The more localized turbulence intensity profile produces stronger Reynolds stress and E Multiplication-Sign B shear flows, which in turn results in more effective turbulence self-regulation. This suggests that models without non-resonant modes may significantly underestimate turbulent fluctuation levels and transport.

  19. Generation of broadband and multiple-peak THz radiation in aperiodically poled lithium niobate

    Institute of Scientific and Technical Information of China (English)

    Fucheng Chen; Xianfeng Chen; Yuping Chen; Yuxing Xia

    2005-01-01

    @@ We theoretically analyze the generation of broadened and multi-peak terahertz (THz) radiation in aperiodically poled lithium niobate (APPLN), whose sequence of opposite domains is optimized by simulated annealing (SA) algorithm. The full-width at half maximum (FWHM) of the broadened THz radiation in our simulation is 0.26 THz. Both of the central wavelength and FWHM can be easily tuned by choosing proper objective functions. THz radiation with wider and flatter FWHM can be achieved by increasing the length of the lithium niobate crystal. The two-peak THz generation is also provided as an example of multi-peak with the central wavelengths at 1.68 and 1.80 THz, respectively.

  20. Generating anagrams from multiple core strings employing user-defined vocabularies and orthographic parameters.

    Science.gov (United States)

    Jordan, Timothy R; Monteiro, Axel

    2003-02-01

    Anagrams are used widely in psychological research. However, generating a range of strings with the same letter content is an inherently difficult and time-consuming task for humans, and current computer-based anagram generators do not provide the controls necessary for psychological research. In this article, we present a computational algorithm that overcomes these problems. Specifically, the algorithm processes automatically each word in a user-defined source vocabulary and outputs, for each word, all possible anagrams that exist as words (or as nonwords, if required) as defined by the same source vocabulary. Moreover, we show how the output of the algorithm can be filtered to produce anagrams within specific user-defined orthographic parameters. For example, the anagrams produced can be filtered to produce words that share, with each other or with other words in the source vocabulary, letters in only certain positions. Finally, we provide free access to the complete Windows-based program and source code containing these facilities for anagram generation.

  1. Electricity generation from tetrathionate in microbial fuel cells by acidophiles

    Energy Technology Data Exchange (ETDEWEB)

    Sulonen, Mira L.K., E-mail: mira.sulonen@tut.fi; Kokko, Marika E.; Lakaniemi, Aino-Maija; Puhakka, Jaakko A.

    2015-03-02

    Highlights: • Electricity can be generated from tetrathionate in MFCs at pH below 2.5. • Tetrathionate disproportionated to sulfate and elemental sulfur. • Biohydrometallurgical process waters contained electrochemically active bacteria. • Acidithiobacillus spp. and Ferroplasma spp. were identified from the MFCs. - Abstract: Inorganic sulfur compounds, such as tetrathionate, are often present in mining process and waste waters. The biodegradation of tetrathionate was studied under acidic conditions in aerobic batch cultivations and in anaerobic anodes of two-chamber flow-through microbial fuel cells (MFCs). All four cultures originating from biohydrometallurgical process waters from multimetal ore heap bioleaching oxidized tetrathionate aerobically at pH below 3 with sulfate as the main soluble metabolite. In addition, all cultures generated electricity from tetrathionate in MFCs at pH below 2.5 with ferric iron as the terminal cathodic electron acceptor. The maximum current and power densities during MFC operation and in the performance analysis were 79.6 mA m{sup −2} and 13.9 mW m{sup −2} and 433 mA m{sup −2} and 17.6 mW m{sup −2}, respectively. However, the low coulombic efficiency (below 5%) indicates that most of the electrons were directed to other processes, such as aerobic oxidation of tetrathionate and unmeasured intermediates. The microbial community analysis revealed that the dominant species both in the anolyte and on the anode electrode surface of the MFCs were Acidithiobacillus spp. and Ferroplasma spp. This study provides a proof of concept that tetrathionate serves as electron donor for biological electricity production in the pH range of 1.2–2.5.

  2. Electricity generation from tetrathionate in microbial fuel cells by acidophiles

    International Nuclear Information System (INIS)

    Highlights: • Electricity can be generated from tetrathionate in MFCs at pH below 2.5. • Tetrathionate disproportionated to sulfate and elemental sulfur. • Biohydrometallurgical process waters contained electrochemically active bacteria. • Acidithiobacillus spp. and Ferroplasma spp. were identified from the MFCs. - Abstract: Inorganic sulfur compounds, such as tetrathionate, are often present in mining process and waste waters. The biodegradation of tetrathionate was studied under acidic conditions in aerobic batch cultivations and in anaerobic anodes of two-chamber flow-through microbial fuel cells (MFCs). All four cultures originating from biohydrometallurgical process waters from multimetal ore heap bioleaching oxidized tetrathionate aerobically at pH below 3 with sulfate as the main soluble metabolite. In addition, all cultures generated electricity from tetrathionate in MFCs at pH below 2.5 with ferric iron as the terminal cathodic electron acceptor. The maximum current and power densities during MFC operation and in the performance analysis were 79.6 mA m−2 and 13.9 mW m−2 and 433 mA m−2 and 17.6 mW m−2, respectively. However, the low coulombic efficiency (below 5%) indicates that most of the electrons were directed to other processes, such as aerobic oxidation of tetrathionate and unmeasured intermediates. The microbial community analysis revealed that the dominant species both in the anolyte and on the anode electrode surface of the MFCs were Acidithiobacillus spp. and Ferroplasma spp. This study provides a proof of concept that tetrathionate serves as electron donor for biological electricity production in the pH range of 1.2–2.5

  3. Weighted Hashing with Multiple Cues for Cell-Level Analysis of Histopathological Images.

    Science.gov (United States)

    Zhang, Xiaofan; Su, Hai; Yang, Lin; Zhang, Shaoting

    2015-01-01

    Recently, content-based image retrieval has been investigated for histopathological image analysis, focusing on improving the accuracy and scalability. The main motivation is to interpret a new image (i.e., query image) by searching among a potentially large-scale database of training images in real-time. Hashing methods have been employed because of their promising performance. However, most previous works apply hashing algorithms on the whole images, while the important information of histopathological images usually lies in individual cells. In addition, they usually only hash one type of features, even though it is often necessary to inspect multiple cues of cells. Therefore, we propose a probabilistic-based hashing framework to model multiple cues of cells for accurate analysis of histopathological images. Specifically, each cue of a cell is compressed as binary codes by kernelized and supervised hashing, and the importance of each hash entry is determined adaptively according to its discriminativity, which can be represented as probability scores. Given these scores, we also propose several feature fusion and selection schemes to integrate their strengths. The classification of the whole image is conducted by aggregating the results from multiple cues of all cells. We apply our algorithm on differentiating adenocarcinoma and squamous carcinoma, i.e., two types of lung cancers, using a large dataset containing thousands of lung microscopic tissue images. It achieves 90.3% accuracy by hashing and retrieving multiple cues of half-million cells.

  4. Hollow fiber integrated microfluidic platforms for in vitro Co-culture of multiple cell types.

    Science.gov (United States)

    Huang, Jen-Huang; Harris, Jennifer F; Nath, Pulak; Iyer, Rashi

    2016-10-01

    This study demonstrates a rapid prototyping approach for fabricating and integrating porous hollow fibers (HFs) into microfluidic device. Integration of HF can enhance mass transfer and recapitulate tubular shapes for tissue-engineered environments. We demonstrate the integration of single or multiple HFs, which can give the users the flexibility to control the total surface area for tissue development. We also present three microfluidic designs to enable different co-culture conditions such as the ability to co-culture multiple cell types simultaneously on a flat and tubular surface, or inside the lumen of multiple HFs. Additionally, we introduce a pressurized cell seeding process that can allow the cells to uniformly adhere on the inner surface of HFs without losing their viabilities. Co-cultures of lung epithelial cells and microvascular endothelial cells were demonstrated on the different platforms for at least five days. Overall, these platforms provide new opportunities for co-culturing of multiple cell types in a single device to reconstruct native tissue micro-environment for biomedical and tissue engineering research. PMID:27613401

  5. Weighted Hashing with Multiple Cues for Cell-Level Analysis of Histopathological Images.

    Science.gov (United States)

    Zhang, Xiaofan; Su, Hai; Yang, Lin; Zhang, Shaoting

    2015-01-01

    Recently, content-based image retrieval has been investigated for histopathological image analysis, focusing on improving the accuracy and scalability. The main motivation is to interpret a new image (i.e., query image) by searching among a potentially large-scale database of training images in real-time. Hashing methods have been employed because of their promising performance. However, most previous works apply hashing algorithms on the whole images, while the important information of histopathological images usually lies in individual cells. In addition, they usually only hash one type of features, even though it is often necessary to inspect multiple cues of cells. Therefore, we propose a probabilistic-based hashing framework to model multiple cues of cells for accurate analysis of histopathological images. Specifically, each cue of a cell is compressed as binary codes by kernelized and supervised hashing, and the importance of each hash entry is determined adaptively according to its discriminativity, which can be represented as probability scores. Given these scores, we also propose several feature fusion and selection schemes to integrate their strengths. The classification of the whole image is conducted by aggregating the results from multiple cues of all cells. We apply our algorithm on differentiating adenocarcinoma and squamous carcinoma, i.e., two types of lung cancers, using a large dataset containing thousands of lung microscopic tissue images. It achieves 90.3% accuracy by hashing and retrieving multiple cues of half-million cells. PMID:26221682

  6. [Monomorphic post-transplant T-lymphoproliferative disorder after autologous stem cell transplantation for multiple myeloma].

    Science.gov (United States)

    Ishikawa, Tetsuya; Shimizu, Hiroaki; Takei, Toshifumi; Koya, Hiroko; Iriuchishima, Hirono; Hosiho, Takumi; Hirato, Junko; Kojima, Masaru; Handa, Hiroshi; Nojima, Yoshihisa; Murakami, Hirokazu

    2016-01-01

    We report a rare case of T cell type monomorphic post-transplant lymphoproliferative disorders (PTLD) after autologous stem cell transplantation. A 53-year-old man with multiple myeloma received autologous stem cell transplantation and achieved a very good partial response. Nine months later, he developed a high fever and consciousness disturbance, and had multiple swollen lymph nodes and a high titer of Epstein-Barr (EB) virus DNA in his peripheral blood. Neither CT nor MRI of the brain revealed any abnormalities. Cerebrospinal fluid contained no malignant cells, but the EB virus DNA titer was high. Lymph node biopsy revealed T cell type monomorphic PTLD. Soon after high-dose treatment with methotrexate and cytosine arabinoside, the high fever and consciousness disturbance subsided, and the lymph node swelling and EB virus DNA disappeared. Given the efficacy of chemotherapy in this case, we concluded that the consciousness disturbance had been induced by central nervous system involvement of monomorphic PTLD.

  7. Peroxiredoxin 1 knockdown sensitizes cancer cells to reactive oxygen species-generating drugs - an alternative approach for chemotherapy.

    Science.gov (United States)

    He, Tiantian; Hatem, Elie; Vernis, Laurence; Huang, Meng-Er

    2014-10-01

    Peroxiredoxins have multiple cellular functions as major antioxidants, signaling regulators and tumor suppressors. Peroxiredoxin 1 (PRX1) is the most abundant among the six isoforms of human peroxiredoxins, catalyzing the reduction of peroxides utilizing thioredoxin 1as an electron donor. PRX1 is frequently over-expressed in various cancer cells, which is thought to be associated with carcinogenesis, metastasis and resistance to radiotherapy or chemotherapy. We investigated how modulations of intracellular redox system, especially PRX1, affect cancer cell sensitivity to reactive oxygen species (ROS)-generating drugs. We observed that stable and transient Prx1 knockdown (Prx1-) significantly enhances HeLa cell sensitivity to β-lapachone (β-lap), a potential anticancer agent, and to other ROS-generating molecules. ROS accumulation played a crucial role in drug-enhanced Prx1- cell death. For β-lap, Prx1- cells sensitization is achieved through combined action of accumulation of ROS and enhancement of mitogen-activated protein kinase pathway activation. The effect of other ROS-inducing drugs on Prx1- cell survival will also be presented and discussed. Taken together, our data provide evidence that PRX1 could be an interesting anticancer target and modulation of intracellular redox states through PRX1 inhibition could be an alternative approach to enhance cancer cell sensitivity to ROS-generating drugs. PMID:26461286

  8. GiMMiK-Generating bespoke matrix multiplication kernels for accelerators: Application to high-order Computational Fluid Dynamics

    Science.gov (United States)

    Wozniak, Bartosz D.; Witherden, Freddie D.; Russell, Francis P.; Vincent, Peter E.; Kelly, Paul H. J.

    2016-05-01

    Matrix multiplication is a fundamental linear algebra routine ubiquitous in all areas of science and engineering. Highly optimised BLAS libraries (cuBLAS and clBLAS on GPUs) are the most popular choices for an implementation of the General Matrix Multiply (GEMM) in software. In this paper we present GiMMiK-a generator of bespoke matrix multiplication kernels for the CUDA and OpenCL platforms. GiMMiK exploits a prior knowledge of the operator matrix to generate highly performant code. The performance of GiMMiK's kernels is particularly apparent in a block-by-panel type of matrix multiplication, where the block matrix is typically small (e.g. dimensions of 96 × 64). Such operations are characteristic to our motivating application in PyFR-an implementation of Flux Reconstruction schemes for high-order fluid flow simulations on mixed unstructured meshes. GiMMiK fully unrolls the matrix-vector product and embeds matrix entries directly in the code to benefit from the use of the constant cache and compiler optimisations. Further, it reduces the number of floating-point operations by removing multiplications by zeros. Together with the ability of our kernels to avoid the poorly optimised cleanup code, executed by library GEMM, we are able to outperform cuBLAS on two NVIDIA GPUs: GTX 780 Ti and Tesla K40c. We observe speedups of our kernels over cuBLAS GEMM of up to 9.98 and 63.30 times for a 294×1029 99% sparse PyFR matrix in double precision on the Tesla K40c and GTX 780 Ti correspondingly. In single precision, observed speedups reach 12.20 and 13.07 times for a 4×8 50% sparse PyFR matrix on the two aforementioned cards. Using GiMMiK as the matrix multiplication kernel provider allows us to achieve a speedup of up to 1.70 (2.19) for a simulation of an unsteady flow over a cylinder executed with PyFR in double (single) precision on the Tesla K40c. All results were generated with GiMMiK version 1.0.

  9. ELECTRICITY GENERATION FROM SWINE WASTEWATER USING MICROBIAL FUEL CELL

    Directory of Open Access Journals (Sweden)

    Chimezie Jason Ogugbue

    2015-11-01

    Full Text Available Electricity generation from swine wastewater using microbial fuel cell (MFC was investigated. Swine wastewater was collected into dual-chambered (aerobic and anaerobic fuel cell. The maximum power output using copper and carbon electrodes were 250.54 and 52.33 µW, while 10.0 and 5.0 cm salt bridge length between the cathode and anode were 279.50 and 355.26 µW, respectively. Potassium permanganate and ordinal water gave a maximum power output of 1287.8 and 13 9.18 µW. MFCs utilize microbial communities to degrade organic materials found within wastewater and converted stored chemical energy to electrical energy in a single step. The initial bacterial and fungal counts were 7.4×106 and 1.1×103 CFU ml-1. Bacterial counts steadily increased with time to 1.40×107 CFU ml-1 while fungal count declined to 4.4×106 CFU ml-1 after day 60. The declined in microbial counts may be attributed to the time necessary for acclimatization of microbes to the anode. The genera identified were Bacillus, Citrobacter, Pseudomonas, Lactobacillus, Escherichia coli, Aspergillus and Rhizopus. These microbes acted as primary and secondary utilizers, utilizing carbon and other organics of the wastewater. Chemical parameters indicated that the biochemical oxygen demand ranged from 91.4–23.2 mg/L, giving 75% while the chemical oxygen demand ranged from 243.1–235.2 mg/L, representing 3.3%. Although, the metabolic activities of microbes were responsible for the observed degradation, leading to electricity, the overall power output depended on the distance between the anode and cathode compartment, types of electrode materials and mediators and oxygen reaction at the cathode.

  10. Incorporating Environmental Justice into Second Generation Indices of Multiple Deprivation: Lessons from the UK and Progress Internationally

    Directory of Open Access Journals (Sweden)

    Jon Fairburn

    2016-07-01

    Full Text Available Second generation area-based indices of multiple deprivation have been extensively used in the UK over the last 15 years. They resulted from significant developments in political, technical, and conceptual spheres for deprivation data. We review the parallel development of environmental justice research and how and when environmental data was incorporated into these indices. We explain the transfer of these methods from the UK to Germany and assess the progress internationally in developing such indices. Finally, we illustrate how billions of pounds in the UK was allocated by using these tools to tackle neighbourhood deprivation and environmental justice to address the determinants of health.

  11. Geometric ortho-rectification and generation of sigma(0) image products from multiple incidence synthetic aperture radar images

    Science.gov (United States)

    Curlander, James; Leberl, Franz; Kruse, Fred

    1992-01-01

    The results of the first phase of a cooperative effort in geometric orthorectification and generation of sigma(0) images of multiple incidence SAR images are presented. The geometric accuracy of the final image products is approximately 18 m or 1.5 pixels. A method for registering radar imagery collected from an airborne platform to an existing digital elevation model despite the effects of unmodeled variations in the flight path of the platform is demonstrated. The results indicate the requirements for a more detailed digital elevation model.

  12. Rogue waves generation via nonlinear soliton collision in multiple-soliton state of a mode-locked fiber laser.

    Science.gov (United States)

    Peng, Junsong; Tarasov, Nikita; Sugavanam, Srikanth; Churkin, Dmitry

    2016-09-19

    We report for the first time, rogue waves generation in a mode-locked fiber laser that worked in multiple-soliton state in which hundreds of solitons occupied the whole laser cavity. Using real-time spatio-temporal intensity dynamics measurements, it is unveiled that nonlinear soliton collision accounts for the formation of rogue waves in this laser state. The nature of interactions between solitons are also discussed. Our observation may suggest similar formation mechanisms of rogue waves in other systems. PMID:27661869

  13. Incorporating Environmental Justice into Second Generation Indices of Multiple Deprivation: Lessons from the UK and Progress Internationally

    Science.gov (United States)

    Fairburn, Jon; Maier, Werner; Braubach, Matthias

    2016-01-01

    Second generation area-based indices of multiple deprivation have been extensively used in the UK over the last 15 years. They resulted from significant developments in political, technical, and conceptual spheres for deprivation data. We review the parallel development of environmental justice research and how and when environmental data was incorporated into these indices. We explain the transfer of these methods from the UK to Germany and assess the progress internationally in developing such indices. Finally, we illustrate how billions of pounds in the UK was allocated by using these tools to tackle neighbourhood deprivation and environmental justice to address the determinants of health. PMID:27472347

  14. Efficient Multiple Exciton Generation Observed in Colloidal PbSe Quantum Dots with Temporally and Spectrally Resolved Intraband Excitation

    KAUST Repository

    Ji, Minbiao

    2009-03-11

    We have spectrally resolved the intraband transient absorption of photogenerated excitons to quantify the exciton population dynamics in colloidal PbSe quantum dots (QDs). These measurements demonstrate that the spectral distribution, as well as the amplitude, of the transient spectrum depends on the number of excitons excited in a QD. To accurately quantify the average number of excitons per QD, the transient spectrum must be spectrally integrated. With spectral integration, we observe efficient multiple exciton generation In colloidal PbSe QDs. © 2009 American Chemical Society.

  15. CD34+ cells cultured in stem cell factor and interleukin-2 generate CD56+ cells with antiproliferative effects on tumor cell lines

    Directory of Open Access Journals (Sweden)

    Hensel Nancy

    2005-04-01

    Full Text Available Abstract In vitro stimulation of CD34+ cells with IL-2 induces NK cell differentiation. In order to define the stages of NK cell development, which influence their generation from CD34 cells, we cultured G-CSF mobilized peripheral blood CD34+ cells in the presence of stem cell factor and IL-2. After three weeks culture we found a diversity of CD56+ subsets which possessed granzyme A, but lacked the cytotoxic apparatus required for classical NK-like cytotoxicity. However, these CD56+ cells had the unusual property of inhibiting proliferation of K562 and P815 cell lines in a cell-contact dependent fashion.

  16. Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma.

    Science.gov (United States)

    Peacock, Craig D; Wang, Qiuju; Gesell, Gregory S; Corcoran-Schwartz, Ian M; Jones, Evan; Kim, Jynho; Devereux, Wendy L; Rhodes, Jonathan T; Huff, Carol A; Beachy, Philip A; Watkins, D Neil; Matsui, William

    2007-03-01

    The cancer stem cell hypothesis suggests that malignant growth depends on a subset of tumor cells with stem cell-like properties of self-renewal. Because hedgehog (Hh) signaling regulates progenitor cell fate in normal development and homeostasis, aberrant pathway activation might be involved in the maintenance of such a population in cancer. Indeed, mutational activation of the Hh pathway is associated with medulloblastoma and basal cell carcinoma; pathway activity is also critical for growth of other tumors lacking such mutations, although the mechanism of pathway activation is poorly understood. Here we study the role and mechanism of Hh pathway activation in multiple myeloma (MM), a malignancy with a well defined stem cell compartment. In this model, rare malignant progenitors capable of clonal expansion resemble B cells, whereas the much larger tumor cell population manifests a differentiated plasma cell phenotype that pathologically defines the disease. We show that the subset of MM cells that manifests Hh pathway activity is markedly concentrated within the tumor stem cell compartment. The Hh ligand promotes expansion of MM stem cells without differentiation, whereas the Hh pathway blockade, while having little or no effect on malignant plasma cell growth, markedly inhibits clonal expansion accompanied by terminal differentiation of purified MM stem cells. These data reveal that Hh pathway activation is heterogeneous across the spectrum of MM tumor stem cells and their more differentiated progeny. The potential existence of similar relationships in other adult cancers may have important biologic and clinical implications for the study of aberrant Hh signaling.

  17. Basalt generation at the Apollo 12 site. Part 2: Source heterogeneity, multiple melts, and crustal contamination

    Science.gov (United States)

    Neal, Clive R.; Hacker, Matthew D.; Snyder, Gregory A.; Taylor, Lawrence A.; Liu, Yun-Gang; Schmitt, Roman A.

    1994-01-01

    The petrogenesis of Apollo 12 mare basalts has been examined with emphasis on trace-element ratios and abundances. Vitrophyric basalts were used as parental compositions for the modeling, and proportions of fractionating phases were determined using the MAGFOX prograqm of Longhi (1991). Crystal fractionation processes within crustal and sub-crustal magma chambers are evaluated as a function of pressure. Knowledge of the fractionating phases allows trace-element variations to be considered as either source related or as a product of post-magma-generation processes. For the ilmenite and olivine basalts, trace-element variations are inherited from the source, but the pigeonite basalt data have been interpreted with open-system evolution processes through crustal assimilation. Three groups of basalts have been examined: (1) Pigeonite basalts-produced by the assimilation of lunar crustal material by a parental melt (up to 3% assimilation and 10% crystal fractionation, with an 'r' value of 0.3). (2) Ilmenite basalts-produced by variable degrees of partial melting (4-8%) of a source of olivine, pigeonite, augite, and plagioclase, brought together by overturn of the Lunar Magma Ocean (LMO) cumulate pile. After generation, which did not exhaust any of the minerals in the source, these melts experienced closed-system crystal fractionation/accumulation. (3) Olivine basalts-produced by variable degrees of partial melting (5-10%) of a source of olivine, pigeonite, and augite. After generation, again without exhausting any of the minerals in the source, these melts evolved through crystal accumulation. The evolved liquid counterparts of these cumulates have not been sampled. The source compositions for the ilmenite and olivine basalts were calculated by assuming that the vitrophyric compositions were primary and the magmas were produced by non-modal batch melting. Although the magnitude is unclear, evaluation of these source regions indicates that both be composed of early- and

  18. Multiple exciton generation in nano-crystals revisited: Consistent calculation of the yield based on pump-probe spectroscopy

    CERN Document Server

    Karki, Khadga J; Zheng, Kaibo; Zidek, Karel; Mousa, Abdelrazek; Abdellah, Mohamed A; Messing, Maria; Wallenberg, L Reine; Yartsev, Arkadi; Pullerits, Tonu

    2013-01-01

    Multiple exciton generation (MEG) is a process in which more than one exciton is generated upon the absorption of a high energy photon, typically higher than two times the band gap, in semiconductor nanocrystals. It can be observed experimentally using time resolved spectroscopy such as the transient absorption measurements. Quantification of the MEG yield is usu- ally done by assuming that the bi-exciton signal is twice the signal from a single exciton. Herein we show that this assumption is not always justified and may lead to significant errors in the estimated MEG yields. We develop a methodology to determine proper scaling factors to the signals from the transient absorption experiments. Using the methodology we find modest MEG yields in lead chalcogenide nanocrystals including the nanorods.

  19. Fast high-resolution computer-generated hologram computation using multiple graphics processing unit cluster system.

    Science.gov (United States)

    Takada, Naoki; Shimobaba, Tomoyoshi; Nakayama, Hirotaka; Shiraki, Atsushi; Okada, Naohisa; Oikawa, Minoru; Masuda, Nobuyuki; Ito, Tomoyoshi

    2012-10-20

    To overcome the computational complexity of a computer-generated hologram (CGH), we implement an optimized CGH computation in our multi-graphics processing unit cluster system. Our system can calculate a CGH of 6,400×3,072 pixels from a three-dimensional (3D) object composed of 2,048 points in 55 ms. Furthermore, in the case of a 3D object composed of 4096 points, our system is 553 times faster than a conventional central processing unit (using eight threads).

  20. Collective force generated by multiple biofilaments can exceed the sum of forces due to individual ones

    CERN Document Server

    Das, Dipjyoti; Padinhateeri, Ranjith

    2013-01-01

    Collective dynamics and force generation by cytoskeletal filaments are crucial in many cellular processes. Investigating growth dynamics of a bundle of N independent cytoskeletal filaments pushing against a wall, we show that ATP/GTP hydrolysis leads to a collective phenomena that is currently unknown. Obtaining force-velocity relations for different models that capture chemical switching, we show, analytically and numerically, that the collective stall force of N filaments is greater than N times the stall force of a single filament. Simulating growing actin and microtubule bundles, considering both sequential and random hydrolysis, we make quantitative predictions of the excess forces.

  1. Carbon fiber enhanced bioelectricity generation in soil microbial fuel cells.

    Science.gov (United States)

    Li, Xiaojing; Wang, Xin; Zhao, Qian; Wan, Lili; Li, Yongtao; Zhou, Qixing

    2016-11-15

    The soil microbial fuel cell (MFC) is a promising biotechnology for the bioelectricity recovery as well as the remediation of organics contaminated soil. However, the electricity production and the remediation efficiency of soil MFC are seriously limited by the tremendous internal resistance of soil. Conductive carbon fiber was mixed with petroleum hydrocarbons contaminated soil and significantly enhanced the performance of soil MFC. The maximum current density, the maximum power density and the accumulated charge output of MFC mixed carbon fiber (MC) were 10, 22 and 16 times as high as those of closed circuit control due to the carbon fiber productively assisted the anode to collect the electron. The internal resistance of MC reduced by 58%, 83% of which owed to the charge transfer resistance, resulting in a high efficiency of electron transfer from soil to anode. The degradation rates of total petroleum hydrocarbons enhanced by 100% and 329% compared to closed and opened circuit controls without the carbon fiber respectively. The effective range of remediation and the bioelectricity recovery was extended from 6 to 20cm with the same area of air-cathode. The mixed carbon fiber apparently enhanced the bioelectricity generation and the remediation efficiency of soil MFC by means of promoting the electron transfer rate from soil to anode. The use of conductively functional materials (e.g. carbon fiber) is very meaningful for the remediation and bioelectricity recovery in the bioelectrochemical remediation.

  2. Carbon fiber enhanced bioelectricity generation in soil microbial fuel cells.

    Science.gov (United States)

    Li, Xiaojing; Wang, Xin; Zhao, Qian; Wan, Lili; Li, Yongtao; Zhou, Qixing

    2016-11-15

    The soil microbial fuel cell (MFC) is a promising biotechnology for the bioelectricity recovery as well as the remediation of organics contaminated soil. However, the electricity production and the remediation efficiency of soil MFC are seriously limited by the tremendous internal resistance of soil. Conductive carbon fiber was mixed with petroleum hydrocarbons contaminated soil and significantly enhanced the performance of soil MFC. The maximum current density, the maximum power density and the accumulated charge output of MFC mixed carbon fiber (MC) were 10, 22 and 16 times as high as those of closed circuit control due to the carbon fiber productively assisted the anode to collect the electron. The internal resistance of MC reduced by 58%, 83% of which owed to the charge transfer resistance, resulting in a high efficiency of electron transfer from soil to anode. The degradation rates of total petroleum hydrocarbons enhanced by 100% and 329% compared to closed and opened circuit controls without the carbon fiber respectively. The effective range of remediation and the bioelectricity recovery was extended from 6 to 20cm with the same area of air-cathode. The mixed carbon fiber apparently enhanced the bioelectricity generation and the remediation efficiency of soil MFC by means of promoting the electron transfer rate from soil to anode. The use of conductively functional materials (e.g. carbon fiber) is very meaningful for the remediation and bioelectricity recovery in the bioelectrochemical remediation. PMID:27162144

  3. Electricity generation from rapeseed straw hydrolysates using microbial fuel cells.

    Science.gov (United States)

    Jablonska, Milena A; Rybarczyk, Maria K; Lieder, Marek

    2016-05-01

    Rapeseed straw is an attractive fuel material for microbial fuel cells (MFCs) due to its high content of carbohydrates (more than 60% carbohydrates). This study has demonstrated that reducing sugars can be efficiently extracted from raw rapeseed straw by combination of hydrothermal pretreatment and enzymatic hydrolysis followed by utilization as a fuel in two-chamber MFCs for electrical power generation. The most efficient method of saccharification of this lignocellulosic biomass (17%) turned out hydrothermal pretreatment followed by enzymatic hydrolysis. Electricity was produced using hydrolysate concentrations up to 150 mg/dm(3). The power density reached 54 mW/m(2), while CEs ranged from 60% to 10%, corresponding to the initial reducing sugar concentrations of 10-150 mg/dm(3). The COD degradation rates based on charge calculation increased from 0.445 g COD/m(2)/d for the hydrolysate obtained with the microwave treatment to 0.602 g COD/m(2)/d for the most efficient combination of hydrothermal treatment followed by enzymatic hydrolysis.

  4. Electricity generation from tetrathionate in microbial fuel cells by acidophiles.

    Science.gov (United States)

    Sulonen, Mira L K; Kokko, Marika E; Lakaniemi, Aino-Maija; Puhakka, Jaakko A

    2015-03-01

    Inorganic sulfur compounds, such as tetrathionate, are often present in mining process and waste waters. The biodegradation of tetrathionate was studied under acidic conditions in aerobic batch cultivations and in anaerobic anodes of two-chamber flow-through microbial fuel cells (MFCs). All four cultures originating from biohydrometallurgical process waters from multimetal ore heap bioleaching oxidized tetrathionate aerobically at pH below 3 with sulfate as the main soluble metabolite. In addition, all cultures generated electricity from tetrathionate in MFCs at pH below 2.5 with ferric iron as the terminal cathodic electron acceptor. The maximum current and power densities during MFC operation and in the performance analysis were 79.6 mA m(-2) and 13.9 mW m(-2) and 433 mA m(-2) and 17.6 mW m(-2), respectively. However, the low coulombic efficiency (below 5%) indicates that most of the electrons were directed to other processes, such as aerobic oxidation of tetrathionate and unmeasured intermediates. The microbial community analysis revealed that the dominant species both in the anolyte and on the anode electrode surface of the MFCs were Acidithiobacillus spp. and Ferroplasma spp. This study provides a proof of concept that tetrathionate serves as electron donor for biological electricity production in the pH range of 1.2-2.5.

  5. A Multiple Z-Pinch Configuration for the Generation of High-Density, Magnetized Plasmas

    Science.gov (United States)

    Tarditi, Alfonso G.

    2015-11-01

    The z-pinch is arguably the most straightforward and economical approach for the generation and confinement of hot plasmas, with a long history of theoretical investigations and experimental developments. While most of the past studies were focused on countering the natural tendency of z-pinches to develop instabilities, this study attempts to take advantage of those unstable regimes to form a quasi-stable plasma, with higher density and temperature, possibly of interest for a fusion reactor concept. For this purpose, a configuration with four z-pinch discharges, with axis parallel to each other and symmetrically positioned, is considered. Electrodes for the generation of the discharges and magnetic coils are arranged to favor the formation of concave discharge patterns. The mutual attraction from the co-streaming discharge currents enhances this pattern, leading to bent plasma streams, all nearing towards the axis. This configuration is intended to excite and sustain a ``kink'' unstable mode for each z-pinch, eventually producing either plasmoid structures, detached from each discharge, or sustained kink patterns: both these cases appear to lead to plasmas merging in the central region. The feasibility of this approach in creating a higher density, hotter, meta-stable plasma regime is investigated computationally, addressing both the kink excitation phase and the dynamics of the converging plasma columns.

  6. CD8+ T cells cause disability and axon loss in a mouse model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Chandra Deb

    Full Text Available BACKGROUND: The objective of this study was to test the hypothesis that CD8+ T cells directly mediate motor disability and axon injury in the demyelinated central nervous system. We have previously observed that genetic deletion of the CD8+ T cell effector molecule perforin leads to preservation of motor function and preservation of spinal axons in chronically demyelinated mice. METHODOLOGY/PRINCIPAL FINDINGS: To determine if CD8+ T cells are necessary and sufficient to directly injure demyelinated axons, we adoptively transferred purified perforin-competent CD8+ spinal cord-infiltrating T cells into profoundly demyelinated but functionally preserved perforin-deficient host mice. Transfer of CD8+ spinal cord-infiltrating T cells rapidly and irreversibly impaired motor function, disrupted spinal cord motor conduction, and reduced the number of medium- and large-caliber spinal axons. Likewise, immunodepletion of CD8+ T cells from chronically demyelinated wildtype mice preserved motor function and limited axon loss without altering other disease parameters. CONCLUSIONS/SIGNIFICANCE: In multiple sclerosis patients, CD8+ T cells outnumber CD4+ T cells in active lesions and the number of CD8+ T cells correlates with the extent of ongoing axon injury and functional disability. Our findings suggest that CD8+ T cells may directly injure demyelinated axons and are therefore a viable therapeutic target to protect axons and motor function in patients with multiple sclerosis.

  7. Generation model of positional values as cell operation during the development of multicellular organisms.

    Science.gov (United States)

    Ogawa, Ken-ichiro; Miyake, Yoshihiro

    2011-03-01

    Many conventional models have used the positional information hypothesis to explain each elementary process of morphogenesis during the development of multicellular organisms. Their models assume that the steady concentration patterns of morphogens formed in an extracellular environment have an important property of positional information, so-called "robustness". However, recent experiments reported that a steady morphogen pattern, the concentration gradient of the Bicoid protein, during early Drosophila embryonic development is not robust for embryo-to-embryo variability. These reports encourage a reconsideration of a long-standing problem in systematic cell differentiation: what is the entity of positional information for cells? And, what is the origin of the robust boundary of gene expression? To address these problems at a cellular level, in this article we pay attention to the re-generative phenomena that show another important property of positional information, "size invariance". In view of regenerative phenomena, we propose a new mathematical model to describe the generation mechanism of a spatial pattern of positional values. In this model, the positional values are defined as the values into which differentiable cells transform a spatial pattern providing positional information. The model is mathematically described as an associative algebra composed of various terms, each of which is the multiplication of some fundamental operators under the assumption that the operators are derived from the remarkable properties of cell differentiation on an amputation surface in regenerative phenomena. We apply this model to the concentration pattern of the Bicoid protein during the anterior-posterior axis formation in Drosophila, and consider the conditions needed to establish the robust boundary of the expression of the hunchback gene. PMID:21167904

  8. Multiple nephron-sparing procedures in solitary kidney with recurrent, metachronous, nonfamilial renal cell carcinoma.

    Science.gov (United States)

    Nosnik, Israel P; Mouraviev, Vladimir; Nelson, Rendon; Polascik, Thomas J

    2006-12-01

    Patients with metachronous bilateral renal cell carcinoma pose a significant challenge given the high mortality of renal cell carcinoma and the poor quality of life should dialysis become necessary. In addition, patients may be subject to morbidity due to potential multiple treatments of the multifocal renal tumors. We present the case of a 71-year-old woman with multifocal, bilateral clear cell carcinoma who maintained a minimal change in serum creatinine after undergoing unilateral radical nephrectomy, subsequent percutaneous radiofrequency ablation, percutaneous cryoablation, laparoscopic cryoablation, and open partial nephrectomy for recurrent renal cell carcinoma in a solitary kidney.

  9. Adult T-cell leukemia/lymphoma presenting multiple lymphomatous polyposis

    Institute of Scientific and Technical Information of China (English)

    Akira Hokama; Nobuyuki Takasu; Jiro Fujita; Takeaki Tomoyose; Yu-ichi Yamamoto; Takako Watanabe; Tetsuo Hirata; Fukunori Kinjo; Seiya Kato; Koichi Ohshima; Hiroshi Uezato

    2008-01-01

    Multiple lymphomatous polyposis (HLP) is an unusual form of non-Hodgkin's lymphoma characterized by polyps throughout the gastrointestinal tract. It has been reported that most MLP are observed in cases with mantle cell lymphoma of B-cell type. We herein present a case of a 66-year-old man with adult T-cell leukemia/lymphoma (ATLL). Colonoscopy revealed MLP throughout the colon and histopathological findings of ATLL cell infiltration. The patient died despite combination of chemotherapy. The literature of manifestations of colonic involvement of ATLL is reviewed and the importance of endoscopic evaluation to differentiate ATLL intestinal lesions from opportunistic infectious enterocolitis is discussed.

  10. Generation of Alveolar Epithelial Spheroids via Isolated Progenitor Cells from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Shimpei Gotoh

    2014-09-01

    Full Text Available No methods for isolating induced alveolar epithelial progenitor cells (AEPCs from human embryonic stem cells (hESCs and induced pluripotent stem cells (hiPSCs have been reported. Based on a study of the stepwise induction of alveolar epithelial cells (AECs, we identified carboxypeptidase M (CPM as a surface marker of NKX2-1+ “ventralized” anterior foregut endoderm cells (VAFECs in vitro and in fetal human and murine lungs. Using SFTPC-GFP reporter hPSCs and a 3D coculture system with fetal human lung fibroblasts, we showed that CPM+ cells isolated from VAFECs differentiate into AECs, demonstrating that CPM is a marker of AEPCs. Moreover, 3D coculture differentiation of CPM+ cells formed spheroids with lamellar-body-like structures and an increased expression of surfactant proteins compared with 2D differentiation. Methods to induce and isolate AEPCs using CPM and consequently generate alveolar epithelial spheroids would aid human pulmonary disease modeling and regenerative medicine.

  11. Killing multiple myeloma cells with the small molecule 3-bromopyruvate: implications for therapy.

    Science.gov (United States)

    Majkowska-Skrobek, Grażyna; Augustyniak, Daria; Lis, Paweł; Bartkowiak, Anna; Gonchar, Mykhailo; Ko, Young H; Pedersen, Peter L; Goffeau, Andre; Ułaszewski, Stanisław

    2014-07-01

    The small molecule 3-bromopyruvate (3-BP), which has emerged recently as the first member of a new class of potent anticancer agents, was tested for its capacity to kill multiple myeloma (MM) cancer cells. Human MM cells (RPMI 8226) begin to lose viability significantly within 8 h of incubation in the presence of 3-BP. The Km (0.3 mmol/l) for intracellular accumulation of 3-BP in MM cells is 24 times lower than that in control cells (7.2 mmol/l). Therefore, the uptake of 3-BP by MM cells is significantly higher than that by peripheral blood mononuclear cells. Further, the IC50 values for human MM cells and control peripheral blood mononuclear cells are 24 and 58 µmol/l, respectively. Therefore, specificity and selectivity of 3-BP toward MM cancer cells are evident on the basis of the above. In MM cells the transcription levels of the gene encoding the monocarboxylate transporter MCT1 is significantly amplified compared with control cells. The level of intracellular ATP in MM cells decreases by over 90% within 1 h after addition of 100 µmol/l 3-BP. The cytotoxicity of 3-BP, exemplified by a marked decrease in viability of MM cells, is potentiated by the inhibitor of glutathione synthesis buthionine sulfoximine. In addition, the lack of mutagenicity and its superior capacity relative to Glivec to kill MM cancer cells are presented in this study. PMID:24557015

  12. Generation of Corneal Keratocytes from Human Embryonic Stem Cells.

    Science.gov (United States)

    Hertsenberg, Andrew J; Funderburgh, James L

    2016-01-01

    Human Embryonic Stem Cells (hESC) offer an important resource as a limitless supply of any differentiated cell type of the human body. Keratocytes, cells from the corneal stroma, may have the potential for restoration of vision in cell therapy and biomedical engineering applications, but these specialized cells are not readily expanded in vitro. Here we describe a two-part method to produce keratocytes from the H1 hESC cell line. The hESC cells, maintained and expanded in feeder-free culture medium are first differentiated to neural crest cells using the stromal-derived inducing activity (SDIA) of the PA6 mouse embryonic fibroblast cell line. The resulting neural crest cells are selected by their expression of cell-surface CD271 and subsequently cultured as 3D pellets in a defined differentiation medium to induce a keratocyte phenotype.

  13. Multiple processes generate productivity-diversity relationships in experimental wood-fall communities.

    Science.gov (United States)

    McClain, Craig R; Barry, James P; Eernisse, Douglas; Horton, Tammy; Judge, Jenna; Kakui, Keiichi; Mah, Chris; Warén, Anders

    2016-04-01

    Energy availability has long been recognized as a predictor of community structure, and changes in both terrestrial and marine productivity under climate change necessitate a deeper understanding of this relationship. The productivity-diversity relationship (PDR) is well explored in both empirical and theoretical work in ecology, but numerous questions remain. Here, we test four different theories for PDRs (More-Individuals Hypothesis, Resource-Ratio Theory, More Specialization Theory, and the Connectivity-Diversity Hypothesis) with experimental deep-sea wood falls. We manipulated productivity by altering wood-fall sizes and measured responses after 5 and 7 years. In November 2006, 32 Acacia sp. logs were deployed at 3203 m in the Northeast Pacific Ocean (Station Deadwood: 36.154098 degrees N, 122.40852 degrees W). Overall, we found a significant increase in diversity with increased wood-fall size for these communities. Increases in diversity with wood-fall size occurred because of the addition of rare species and increases of overall abundance, although individual species responses varied. We also found that limited dispersal helped maintain the positive PDR relationship. Our experiment suggests that multiple interacting mechanisms influence PDRs. PMID:27220205

  14. Reduced Test Pattern Generation of Multiple SIC Vectors with Input and Output Delay Faults

    Directory of Open Access Journals (Sweden)

    P.T.Sairam

    2014-11-01

    Full Text Available In recent years, the design for low power has become one of the greatest challenges in high-performance very large scale integration (VLSI design. Most of the methods focus on the power consumption during normal mode operation, while test mode operation has not normally been a predominant concern. However, it has been found that the power consumed during test mode operation is often much higher than during normal mode operation [1]. This is because most of the consumed power results from the switching activity in the nodes of the circuit under test (CUT, which is much higher during test mode than during normal mode operation [1]–[3]. In the proposed pattern, each generated vector applied to each scan chain is an SIC vector, which can minimize the input transition and reduce test power. In VLSI testing, power reduction is achieved by increasing the correlation between consecutive test patterns.

  15. Flow cytometric assay detecting cytotoxicity against human endogenous retrovirus antigens expressed on cultured multiple sclerosis cells

    DEFF Research Database (Denmark)

    Møller-Larsen, A; Brudek, T; Petersen, T;

    2013-01-01

    as control antibody. Without antibodies this system is suitable for analyses of natural killer cell activity. In optimization of the assay we have used effector lymphocytes from healthy donors. The most effective effector cells are CD56(+) cells. CD8(+) T cells also express CD107a in ADCC. Using the adapted......Damage of target cells by cytotoxicity, either mediated by specific lymphocytes or via antibody-dependent reactions, may play a decisive role in causing the central nervous system (CNS) lesions seen in multiple sclerosis (MS). Relevant epitopes, antibodies towards these epitopes and a reliable...... assay are all mandatory parts in detection and evaluation of the pertinence of such cytotoxicity reactions. We have adapted a flow cytometry assay detecting CD107a expression on the surface of cytotoxic effector cells to be applicable for analyses of the effect on target cells from MS patients...

  16. Effect of Natalizumab on Circulating CD4(+) T-Cells in Multiple Sclerosis

    DEFF Research Database (Denmark)

    Börnsen, Lars; Christensen, Jeppe Romme; Ratzer, Rikke;

    2012-01-01

    In multiple sclerosis (MS), treatment with the monoclonal antibody natalizumab effectively reduces the formation of acute lesions in the central nervous system (CNS). Natalizumab binds the integrin very late antigen (VLA)-4, expressed on the surface of immune cells, and inhibits VLA-4 dependent......-cells due to reduced extravasation of activated and pro-inflammatory T-cells or due to induction of VLA-4 mediated co-stimulatory signals by natalizumab. In this study we examined how natalizumab treatment altered the distribution of effector and memory T-cell subsets in the blood compartment and if T......(HIGH) T-cells, in blood, and natalizumab decreased the expression of CD134 on MBP-reactive CD26(HIGH)CD4(+) T-cells in vitro. Otherwise CD4(+) T-cells from natalizumab-treated and untreated MS patients showed similar responses to MBP. In conclusion natalizumab treatment selectively increased...

  17. 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...

  18. Determination of cell survival after irradiation via clonogenic assay versus multiple MTT Assay - A comparative study

    International Nuclear Information System (INIS)

    For studying proliferation and determination of survival of cancer cells after irradiation, the multiple MTT assay, based on the reduction of a yellow water soluble tetrazolium salt to a purple water insoluble formazan dye by living cells was modified from a single-point towards a proliferation assay. This assay can be performed with a large number of samples in short time using multi-well-plates, assays can be performed semi-automatically with a microplate reader. Survival, the calculated parameter in this assay, is determined mathematically. Exponential growth in both control and irradiated groups was proven as the underlying basis of the applicability of the multiple MTT assay. The equivalence to a clonogenic survival assay with its disadvantages such as time consumption was proven in two setups including plating of cells before and after irradiation. Three cell lines (A 549, LN 229 and F 98) were included in the experiment to study its principal and general applicability

  19. Complex heterogeneous tissue constructs containing multiple cell types prepared by inkjet printing technology.

    Science.gov (United States)

    Xu, Tao; Zhao, Weixin; Zhu, Jian-Ming; Albanna, Mohammad Z; Yoo, James J; Atala, Anthony

    2013-01-01

    This study was designed to develop a versatile method for fabricating complex and heterogeneous three-dimensional (3D) tissue constructs using simultaneous ink-jetting of multiple cell types. Human amniotic fluid-derived stem cells (hAFSCs), canine smooth muscle cells (dSMCs), and bovine aortic endothelial cells (bECs), were separately mixed with ionic cross-linker calcium chloride (CaCl(2)), loaded into separate ink cartridges and printed using a modified thermal inkjet printer. The three cell types were delivered layer-by-layer to pre-determined locations in a sodium alginate-collagen composite located in a chamber under the printer. The reaction between CaCl(2) and sodium alginate resulted in a rapid formation of a solid composite gel and the printed cells were anchored in designated areas within the gel. The printing process was repeated for several cycles leading to a complex 3D multi-cell hybrid construct. The biological functions of the 3D printed constructs were evaluated in vitro and in vivo. Each of the printed cell types maintained their viability and normal proliferation rates, phenotypic expression, and physiological functions within the heterogeneous constructs. The bioprinted constructs were able to survive and mature into functional tissues with adequate vascularization in vivo. These findings demonstrate the feasibility of fabricating complex heterogeneous tissue constructs containing multiple cell types using inkjet printing technology.

  20. Multiple metastatic basal cell carcinoma with concurrent metastatic pleomorphic sarcoma in chronic lymphedema area - Case report *

    OpenAIRE

    Giuliano da Paz Oliveira; Régio José Santiago Girão; Cléverson Teixeira Soares; Edgard Jose Franco Mello Junior

    2012-01-01

    Chronic lymphedema presents as interstitial fluid retention due to a failure in the lymphatic system drainage. The affected region becomes more vulnerable immunologically and predisposed to the onset of neoplasms. Basal Cell Carcinoma is the most common sort of neoplasm, nevertheless it rarely metastisizes. Sarcomas are malignant mesenchymal neoplasms, locally aggressive, which can spread. Here is reported an infrequent case of multiple basal cell carcinoma, synchronous to a poorly differenti...

  1. Determination of cell survival after irradiation via clonogenic assay versus multiple MTT Assay - A comparative study

    OpenAIRE

    Buch Karl; Peters Tanja; Nawroth Thomas; Sänger Markus; Schmidberger Heinz; Langguth Peter

    2012-01-01

    Abstract For studying proliferation and determination of survival of cancer cells after irradiation, the multiple MTT assay, based on the reduction of a yellow water soluble tetrazolium salt to a purple water insoluble formazan dye by living cells was modified from a single-point towards a proliferation assay. This assay can be performed with a large number of samples in short time using multi-well-plates, assays can be performed semi-automatically with a microplate reader. Survival, the calc...

  2. Remyelination of the Corpus Callosum by Olfactory Ensheathing Cell in an Experimental Model of Multiple Sclerosis

    OpenAIRE

    Mohammad Azimi Alamouti; Mehrdad Bakhtiyari; Fatemeh Moradi; Tahmineh Mokhtari; Azim Hedayatpour; Fariba Zafari; Mohammad Barbarestani

    2015-01-01

    Multiple Sclerosis (MS) causes loss of the myelin sheath, which leads to loss of neurons. Regeneration of myelin sheath stimulates axon regeneration and neurons’ survival. In this study, olfactory ensheathing cell (OEC) transplantation is investigated to restore myelin sheath in an experimental model of MS in male mice.OECs were isolated from the olfactory mucosa of seven-day-old infant rats and cultured. Then, cells were evaluated and approved by flow cytometry by p75 and GFAP markers. A tot...

  3. Safety and T Cell Modulating Effects of High Dose Vitamin D3 Supplementation in Multiple Sclerosis

    OpenAIRE

    Joost Smolders; Evelyn Peelen; Mariëlle Thewissen; Jan Willem Cohen Tervaert; Paul Menheere; Raymond Hupperts; Jan Damoiseaux

    2010-01-01

    Background A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS). Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS) patients. In the present study, we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures. Methodology/Principal Findings Fifteen RRMS patients were supplemented with 20 000 IU/d vitamin D3 for 12 weeks...

  4. Imaging of multiple myeloma and related monoclonal plasma cell diseases. An update

    International Nuclear Information System (INIS)

    Multiple myeloma is a hematologic disorder characterized by the infiltration and proliferation of monoclonal plasma cells mainly in the bone marrow. The main symptoms are hypercalcemia, renal impairment, cytopenia/anemia and bone disease - summarized as CRAB-criteria. Symptomatic multiple myeloma is consistently preceded by asymptomatic premalignant stages called monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Staging of multiple myeloma is based on the measurement of the monoclonal protein in serum and urine as well as the assessment of impairment of hematopoiesis, renal function and mineralized bone. In the last decade the development of novel therapeutic agents has led to an increase in response rates and survival time of patients with multiple myeloma, which further stresses the value of response assessment by imaging. Cross sectional imaging like MRI and CT is currently replacing conventional radiological surveys in the initial work-up and follow-up of patients with monoclonal plasma cell diseases. The added value of MRI is to improve initial staging by unraveling a diffuse infiltration of bone marrow by plasma cells, a focal pattern or a combination of both. Furthermore, a complete remission of myeloma confirmed by MRI and CT goes along with a better prognosis compared to a complete response based only on serological parameters.

  5. Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells

    Science.gov (United States)

    Yang, Ruifeng; Zheng, Ying; Burrows, Michelle; Liu, Shujing; Wei, Zhi; Nace, Arben; Guo, Wei; Kumar, Suresh; Cotsarelis, George; Xu, Xiaowei

    2014-01-01

    Epithelial stem cells (EpSCs) in the hair follicle bulge are required for hair follicle growth and cycling. The isolation and propagation of human EpSCs for tissue engineering purposes remains a challenge. Here we develop a strategy to differentiate human iPSCs (hiPSCs) into CD200+/ITGA6+ EpSCs that can reconstitute the epithelial components of the hair follicle and interfollicular epidermis. The hiPSC-derived CD200+/ITGA6+ cells show a similar gene expression signature as EpSCs directly isolated from human hair follicles. Human iPSC-derived CD200+/ITGA6+ cells are capable of generating all hair follicle lineages including the hair shaft, and the inner and outer root sheaths in skin reconstitution assays. The regenerated hair follicles possess a KRT15+ stem cell population and produce hair shafts expressing hair specific keratins. These results suggest an approach for generating large numbers of human EpSCs for tissue engineering and new treatments for hair loss, wound healing and other degenerative skin disorders. PMID:24468981

  6. Effect of input multiplicity on the establishment of simian virus 40 persistent infections in rhesus monkey kidney cells.

    Science.gov (United States)

    Norkin, L C

    1977-12-01

    Monolayer cultures of LLC-MK2 rhesus monkey kidney cells become persistently infected with simian virus 40 after infection at input multiplicities of 100, 10, or 1 plaque-forming unit per cell. After 3 weeks, all cells of the cultures infected at a multiplicity of 1 plaque-forming unit per cell produced the simian virus 40 T antigen. In contrast, 8 to 11 weeks elapsed before all the cells in the cultures infected at a multiplicity of 100 plaque-forming units per cell produced T antigen. Defective interfering particles and interferon production were not evident during this time.

  7. Label-free morphology-based prediction of multiple differentiation potentials of human mesenchymal stem cells for early evaluation of intact cells.

    Directory of Open Access Journals (Sweden)

    Hiroto Sasaki

    Full Text Available Precise quantification of cellular potential of stem cells, such as human bone marrow-derived mesenchymal stem cells (hBMSCs, is important for achieving stable and effective outcomes in clinical stem cell therapy. Here, we report a method for image-based prediction of the multiple differentiation potentials of hBMSCs. This method has four major advantages: (1 the cells used for potential prediction are fully intact, and therefore directly usable for clinical applications; (2 predictions of potentials are generated before differentiation cultures are initiated; (3 prediction of multiple potentials can be provided simultaneously for each sample; and (4 predictions of potentials yield quantitative values that correlate strongly with the experimental data. Our results show that the collapse of hBMSC differentiation potentials, triggered by in vitro expansion, can be quantitatively predicted far in advance by predicting multiple potentials, multi-lineage differentiation potentials (osteogenic, adipogenic, and chondrogenic and population doubling potential using morphological features apparent during the first 4 days of expansion culture. In order to understand how such morphological features can be effective for advance predictions, we measured gene-expression profiles of the same early undifferentiated cells. Both senescence-related genes (p16 and p21 and cytoskeleton-related genes (PTK2, CD146, and CD49 already correlated to the decrease of potentials at this stage. To objectively compare the performance of morphology and gene expression for such early prediction, we tested a range of models using various combinations of features. Such comparison of predictive performances revealed that morphological features performed better overall than gene-expression profiles, balancing the predictive accuracy with the effort required for model construction. This benchmark list of various prediction models not only identifies the best morphological feature

  8. A New Cell Block Method for Multiple Immunohistochemical Analysis of Circulating Tumor Cells in Patients with Liver Cancer

    Science.gov (United States)

    Nam, Soo Jeong; Yeo, Hyun Yang; Chang, Hee Jin; Kim, Bo Hyun; Hong, Eun Kyung; Park, Joong-Won

    2016-01-01

    Purpose We developed a new method of detecting circulating tumor cells (CTCs) in liver cancer patients by constructing cell blocks from peripheral blood cells, including CTCs, followed by multiple immunohistochemical analysis. Materials and Methods Cell blockswere constructed from the nucleated cell pellets of peripheral blood afterremoval of red blood cells. The blood cell blocks were obtained from 29 patients with liver cancer, and from healthy donor blood spikedwith seven cell lines. The cell blocks and corresponding tumor tissues were immunostained with antibodies to seven markers: cytokeratin (CK), epithelial cell adhesion molecule (EpCAM), epithelial membrane antigen (EMA), CK18, α-fetoprotein (AFP), Glypican 3, and HepPar1. Results The average recovery rate of spiked SW620 cells from blood cell blocks was 91%. CTCs were detected in 14 out of 29 patients (48.3%); 11/23 hepatocellular carcinomas (HCC), 1/2 cholangiocarcinomas (CC), 1/1 combined HCC-CC, and 1/3 metastatic cancers. CTCs from 14 patients were positive for EpCAM (57.1%), EMA (42.9%), AFP (21.4%), CK18 (14.3%), Gypican3 and CK (7.1%, each), and HepPar1 (0%). Patients with HCC expressed EpCAM, EMA, CK18, and AFP in tissue and/or CTCs, whereas CK, HepPar1, and Glypican3 were expressed only in tissue. Only EMA was significantly associated with the expressions in CTC and tissue. CTC detection was associated with higher T stage and portal vein invasion in HCC patients. Conclusion This cell block method allows cytologic detection and multiple immunohistochemical analysis of CTCs. Our results show that tissue biomarkers of HCC may not be useful for the detection of CTC. EpCAM could be a candidate marker for CTCs in patients with HCC. PMID:27034142

  9. B cell follicle-like structures in multiple sclerosis-with focus on the role of B cell activating factor

    DEFF Research Database (Denmark)

    Morten, Haugen; Frederiksen, Jette L; Vinter, Matilda Degn

    2014-01-01

    B lymphocytes play an important role in the pathogenesis of multiple sclerosis (MS). Follicle-like structures (FLS) have recently been found in the subarachnoid space in the leptomeninges in some patients with secondary progressive MS (SPMS). They contain proliferating B lymphocytes, plasma cells...

  10. Quantification of multiple fault parameters in flexible turbo-generator systems with incomplete rundown vibration data

    Science.gov (United States)

    Lal, Mohit; Tiwari, Rajiv

    2013-12-01

    A turbo-generator system of the modern rotating machinery consists of the driver and driven shafts, which are coupled through flexible couplings and mounted on flexible bearings. Dynamic characterisation of vital machine elements of such rotating machinery is a challenging problem for reliable and accurate response predictions. In this paper, a key intention is to estimate the bearing and coupling dynamic parameters along with residual unbalances at predefined planes, and the misalignment forces and moments at the coupling based on the rundown vibration data. To tackle a practical difficulty of limited measurements and a numerical difficulty of the conventional dynamic condensation in the development of identification algorithm, a novel condensation technique has been implemented especially to overcome measurement of transverse rotational DOFs. Numerical examples are also presented to show the effectiveness of the proposed method. The measurement noise has been added in numerically simulated responses that are used in the present algorithm to identify the parameters and it is found to be robust. Modelling errors of few physical parameters are also considered and estimates are found to be very good.

  11. Seismic Tremor Generated by Multiple Processes, Vatnajökull Glacier, Iceland

    Science.gov (United States)

    Eibl, E. P. S.; Bean, C. J.; Vogfjord, K. S.

    2014-12-01

    Vatnajökull glacier in eastern Iceland covers five volcanic systems in which Bárdarbunga and Grimsvötn are the most active volcanoes. Whilst fluctuating ice cover mitigates against year-round near-field monitoring of the volcanoes, important information can be gleaned from stations deployed at the glacier's edge. Glacial cover significantly increases the complexity of and the solution space for observed seismic signals. For example tremor can be caused by magmatic activity, intra-glacier interactions, melt water flow or hydrothermal boiling. A better understanding of hazard requires a more indepth understanding of the signals generated by these processes at Vatnajökull. We augmented the sparse network in the region with two seven-element broad band seismometer arrays west of Vatnajökull, in Jökulheimar and near Laki respectively. Observed seismic tremor-like transients (< 2 Hz) originating from two cauldrons west of Grimsvötn are directly associated with small flooding events (jökulhaups), as subsequently confirmed by radar and hydrological observations. For larger longer duration floods dominant harmonic tremor frequencies of 2 to 4 Hz are observed, but they change in amplitude and frequency with time, likely reflecting variable feed and flow rates, associated with a moving source. Our aim is to 'fingerprint' these events such that they can be distinguished from seismic tremor signals associated with magmatic activity.

  12. DSM generation using multiple radar data for relief change detection in North Peloponnese

    Science.gov (United States)

    Nikolakopoulos, Konstantinos G.; Kyriou, Aggeliki; Sabatakakis, Nikolaos; Anastassopoulos, Vassilis

    2016-08-01

    Interferometry constitutes a technique of acquisition height information with a range of applications, such as Digital Surface Model (DSM) generation in order to monitoring the Earth's surface. This work is focused on interferometric DSM creation utilizing radar data of Sentinel-1 and TerraSAR-X missions, covering the wider area of Northern Peloponnese. This area is characterized of loose geological formations and intense active tectonics resulting in continuous and intense relief changes. In this context, the accuracy and the update of the DSMs is essential in order to detect and map any terrain change. The selection of Sentinel-1 and TerraSAR-X images was based on the fact that both missions provide timely, with short revisiting period and satisfactory spatial resolution data. In particular, two ranges of radar data from both missions were submitted in interferometric process aimed at DSM creation. The produced DSMs were compared both visually and statistically to a very accurate reference DSM produced from airphotos by the Greek Cadastral. Furthermore, in order to estimate the accuracy of the DSMs and detect variations of terrain's surface, points of known elevation have been used. 2D RMSE, correlation and the percentile value were computed and the results are presented.

  13. Using Flow Electrodes in Multiple Reactors in Series for Continuous Energy Generation from Capacitive Mixing

    KAUST Repository

    Hatzell, Marta C.

    2014-12-09

    Efficient conversion of “mixing energy” to electricity through capacitive mixing (CapMix) has been limited by low energy recoveries, low power densities, and noncontinuous energy production resulting from intermittent charging and discharging cycles. We show here that a CapMix system based on a four-reactor process with flow electrodes can generate constant and continuous energy, providing a more flexible platform for harvesting mixing energy. The power densities were dependent on the flow-electrode carbon loading, with 5.8 ± 0.2 mW m–2 continuously produced in the charging reactor and 3.3 ± 0.4 mW m–2 produced in the discharging reactor (9.2 ± 0.6 mW m–2 for the whole system) when the flow-electrode carbon loading was 15%. Additionally, when the flow-electrode electrolyte ion concentration increased from 10 to 20 g L–1, the total power density of the whole system (charging and discharging) increased to 50.9 ± 2.5 mW m–2.

  14. A primitive study of voxel feature generation by multiple stacked denoising autoencoders for detecting cerebral aneurysms on MRA

    Science.gov (United States)

    Nemoto, Mitsutaka; Hayashi, Naoto; Hanaoka, Shouhei; Nomura, Yukihiro; Miki, Soichiro; Yoshikawa, Takeharu; Ohtomo, Kuni

    2016-03-01

    The purpose of this study is to evaluate the feasibility of a novel feature generation, which is based on multiple deep neural networks (DNNs) with boosting, for computer-assisted detection (CADe). It is hard and time-consuming to optimize the hyperparameters for DNNs such as stacked denoising autoencoder (SdA). The proposed method allows using SdA based features without the burden of the hyperparameter setting. The proposed method was evaluated by an application for detecting cerebral aneurysms on magnetic resonance angiogram (MRA). A baseline CADe process included four components; scaling, candidate area limitation, candidate detection, and candidate classification. Proposed feature generation method was applied to extract the optimal features for candidate classification. Proposed method only required setting range of the hyperparameters for SdA. The optimal feature set was selected from a large quantity of SdA based features by multiple SdAs, each of which was trained using different hyperparameter set. The feature selection was operated through ada-boost ensemble learning method. Training of the baseline CADe process and proposed feature generation were operated with 200 MRA cases, and the evaluation was performed with 100 MRA cases. Proposed method successfully provided SdA based features just setting the range of some hyperparameters for SdA. The CADe process by using both previous voxel features and SdA based features had the best performance with 0.838 of an area under ROC curve and 0.312 of ANODE score. The results showed that proposed method was effective in the application for detecting cerebral aneurysms on MRA.

  15. Systematic identification of yeast cell cycle transcription factors using multiple data sources

    Directory of Open Access Journals (Sweden)

    Li Wen-Hsiung

    2008-12-01

    Full Text Available Abstract Background Eukaryotic cell cycle is a complex process and is precisely regulated at many levels. Many genes specific to the cell cycle are regulated transcriptionally and are expressed just before they are needed. To understand the cell cycle process, it is important to identify the cell cycle transcription factors (TFs that regulate the expression of cell cycle-regulated genes. Results We developed a method to identify cell cycle TFs in yeast by integrating current ChIP-chip, mutant, transcription factor binding site (TFBS, and cell cycle gene expression data. We identified 17 cell cycle TFs, 12 of which are known cell cycle TFs, while the remaining five (Ash1, Rlm1, Ste12, Stp1, Tec1 are putative novel cell cycle TFs. For each cell cycle TF, we assigned specific cell cycle phases in which the TF functions and identified the time lag for the TF to exert regulatory effects on its target genes. We also identified 178 novel cell cycle-regulated genes, among which 59 have unknown functions, but they may now be annotated as cell cycle-regulated genes. Most of our predictions are supported by previous experimental or computational studies. Furthermore, a high confidence TF-gene regulatory matrix is derived as a byproduct of our method. Each TF-gene regulatory relationship in this matrix is supported by at least three data sources: gene expression, TFBS, and ChIP-chip or/and mutant data. We show that our method performs better than four existing methods for identifying yeast cell cycle TFs. Finally, an application of our method to different cell cycle gene expression datasets suggests that our method is robust. Conclusion Our method is effective for identifying yeast cell cycle TFs and cell cycle-regulated genes. Many of our predictions are validated by the literature. Our study shows that integrating multiple data sources is a powerful approach to studying complex biological systems.

  16. Multiple facial basal cell carcinomas in xeroderma pigmentosum treated with topical imiquimod 5% cream.

    Science.gov (United States)

    Yang, Jian-Qiang; Chen, Xian-Yu; Engle, Michelle Yixiao; Wang, Jian-You

    2015-01-01

    Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by solar sensitivity, photophobia, early onset of freckling, and solar-induced cutaneous neoplastic changes. Management of patients with XP is a therapeutic challenge as they usually develop multiple cutaneous malignancies, making surgical therapy difficult, and continue to form skin malignancies at a high rate. We describe a 30-year-old Chinese man with XP who had been previously treated with excision and dermatoplasty. Upon recurrence of multiple superficial, ulcerative, and pigmented lesions, imiquimod 5% cream was recommended for 4 months. His multiple facial lesions demonstrated an excellent response to topical imiquimod 5% cream with minor side effects. This favorable response indicates that topical application of imiquimod 5% cream is an effective means of treating multiple basal cell carcinomas in XP. PMID:25754701

  17. N-cadherin-mediated interaction with multiple myeloma cells inhibits osteoblast differentiation

    NARCIS (Netherlands)

    R.W.J. Groen; M.F.M. de Rooij; K.A. Kocemba; R.M. Reijmers; A. de Haan-Kramer; M.B. Overdijk; L. Aalders; H. Rozemuller; A.C.M. Martens; P.L. Bergsagel; M.J. Kersten; S.T. Pals; M. Spaargaren

    2011-01-01

    Background Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow microenviro

  18. A Case of Mature Natural Killer-Cell Neoplasm Manifesting Multiple Choroidal Lesions: Primary Intraocular Natural Killer-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Yoshiaki Tagawa

    2015-11-01

    Full Text Available Purpose: Natural killer (NK cell neoplasm is a rare disease that follows an acute course and has a poor prognosis. It usually emerges from the nose and appears in the ocular tissue as a metastasis. Herein, we describe a case of NK-cell neoplasm in which the eye was considered to be the primary organ. Case: A 50-year-old female displayed bilateral anterior chamber cells, vitreous opacity, bullous retinal detachment, and multiple white choroidal mass lesions. Although malignant lymphoma or metastatic tumor was suspected, various systemic examinations failed to detect any positive results. A vitrectomy was performed OS; however, histocytological analyses from the vitreous sample showed no definite evidence of malignancy, and IL-10 concentration was low. Enlarged choroidal masses were fused together. Three weeks after the first visit, the patient suddenly developed an attack of fever, night sweat, and hepatic dysfunction, and 5 days later, she passed away due to multiple organ failure. Immunohistochemisty and in situ hybridization revealed the presence of atypical cells positive for CD3, CD56, and Epstein-Barr virus-encoded RNAs, resulting in the diagnosis of NK-cell neoplasm. With the characteristic clinical course, we concluded that this neoplasm was a primary intraocular NK-cell lymphoma. Conclusions: This is the first report to describe primary intraocular NK-cell neoplasm. When we encounter atypical choroidal lesions, we should consider the possibility of NK-cell lymphoma, even though it is a rare disease.

  19. Human embryonic stem cells have enhanced repair of multiple forms of DNA damage

    DEFF Research Database (Denmark)

    Maynard, Scott; Swistowska, Anna Maria; Lee, Jae Wan;

    2008-01-01

    cells compared with various differentiated murine cells. Using single-cell gel electrophoresis (comet assay) we found that human embryonic stem cells (BG01, I6) have more efficient repair of different types of DNA damage (generated from H2O2, UV-C, ionizing radiation, or psoralen) than human primary...... fibroblasts (WI-38, hs27) and, with the exception of UV-C damage, HeLa cells. Microarray gene expression analysis showed that mRNA levels of several DNA repair genes are elevated in human embryonic stem cells compared with their differentiated forms (embryoid bodies). These data suggest that genomic...... maintenance pathways are enhanced in human embryonic stem cells, relative to differentiated human cells....

  20. Effects of arsenic trioxide on voltage-dependent potassium channels and on cell proliferation of human multiple myeloma cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jin; WANG Wei; WEI Qing-fang; FENG Tie-ming; TAN Li-jun; YANG Bao-feng

    2007-01-01

    @@ Arsenic trioxide (ATO) can induce cellular apoptosis and inhibit the activities of multiple myeloma (MM)cells in vitro,1 but how it works is not very clear. Recent studies showed that ATO worked on the voltagedependent potassium channel and L-type calcium channel in myocardial cells,2-5 but the effect of ATO on ion channels of tumor cells was rarely reported. As the potassium channel plays an important role in controlling cell proliferation,6 we studied the effects of ATO on the voltage-dependent potassium current (Ikv) of the voltage-dependent potassium channel in an MM cell line,and probed into the relationship between changes of the Ikv caused by ATO and cell proliferation.

  1. Cell-matrix adhesion characterization using multiple shear stress zones in single stepwise microchannel

    Science.gov (United States)

    Kim, Min-Ji; Doh, Il; Bae, Gab-Yong; Cha, Hyuk-Jin; Cho, Young-Ho

    2014-08-01

    This paper presents a cell chip capable to characterize cell-matrix adhesion by monitoring cell detachment rate. The proposed cell chip can supply multiple levels of shear stress in single stepwise microchannel. As epithelial-mesenchymal transition (EMT), one of hallmarks of cancer metastasis is closely associated to the interaction with extracelluar matrix (ECM), we took advantage of two lung cancer cell models with different adhesion properties to ECM depending their epithelial or mesenchymal properties, including the pair of lung cancer cells with (A549sh) or without E-cadherin expression (A549sh-Ecad), which would be optimal model to examine the alteration of adhesion properties after EMT induction. The cell-matrix adhesion resisting to shear stress appeared to be remarkably differed between lung cancer cells. The detachment rate of epithelial-like H358 and mesenchymal-like H460 cells was 53%-80% and 25%-66% in the shear stress range of 34-60 dyn/cm2, respectively. A549sh-Ecad cells exhibits lower detachment rate (5%-9%) compared to A549sh cells (14%-40%). By direct comparison of adhesion between A549sh and A549sh-Ecad, we demonstrated that A549shE-cad to mimic EMT were more favorable to the ECM attachment under the various levels of shear stress. The present method can be applied to quantitative analysis of tumor cell-ECM adhesion.

  2. Multiple Redundant Effector Mechanisms of CD8+ T Cells Protect against Influenza Infection

    OpenAIRE

    Hamada, Hiromasa; Bassity, Elizabeth; Flies, Amanda; Strutt, Tara M.; Garcia-Hernandez, Maria de Luz; McKinstry, K. Kai; Zou, Tie; Swain, Susan L.; Dutton, Richard W.

    2012-01-01

    We have previously shown that mice challenged with a lethal dose of PR8-OVAI are protected by injection of 4 to 8 × 106 in vitro - generated Tc1 or Tc17 CD8+ effectors. Viral load, lung damage and loss of lung function are all reduced following transfer. Weight loss is reduced and survival increased. We sought here to define the mechanism of this protection. CD8+ effectors exhibit multiple effector activities, perforin-, FasL- and TRAIL- mediated cytotoxicity, secretion of multiple cytokin...

  3. Experimental Evaluation of the Burst Pressure of Steam Generator Tube with Multiple Part-through-wall Cracks

    International Nuclear Information System (INIS)

    Since steam generator (SG) tube is a pressure boundary of pressurized water reactor (PWR), the maintaining integrity of SG tube is very important. However, various types of defect caused by a mechanical and chemical degradations have been observed in the SG tube. In particular, the outer diameter stress corrosion cracking (ODSCC) in the secondary side is a dominant type of defect, which can lead to leakage of primary coolant and burst of SG tube. Thus, the integrity evaluation of SG tubes with SCC is considered to be an important issue. A number of experimental and analytical studies have been conducted to evaluate burst pressure of SG tube with defects and proposed evaluation models. But, most of the models were developed based on single cracks, although SCC initiates and grows at multiple sites on the surface of SG tube. Therefore, this study carried out burst tests using SG tube specimens containing multiple part-trough-wall (PTW) flaws at room temperature (RT) and evaluated burst pressure of SG tubes with multiple PTW flaws. The burst tests were conducted on 56 specimens and burst pressures were obtained. Also, failure mode of SG tube with multiple flaws was investigated by examining the shape of crack and tearing from post-test specimens. The reduction was more pronounced for L=25.4mm than L=6.3mm and was more pronounced when three flaws were arranged than when two flaws were arranged. Burst pressure increased with increasing axial distance between flaws for collinear multiple flaws, whereas the pressure decreased and saturated with increasing circumferential distance between non-aligned multiple flaws. For SG tubes with parallel multiple flaws, the burst pressure was influenced by circumferential distance between flaws and length of flaws. When two flaws were parallel with circumferential distance of l1=1mm, the burst pressure was higher about 2% than that of single flaw for L=6.3mm, but it was lower about 7% than that of single flaw for L=25.4mm. Thus an

  4. In Vivo Monitoring of Multiple Circulating Cell Populations Using Two-photon Flow Cytometry.

    Science.gov (United States)

    Tkaczyk, Eric R; Zhong, Cheng Frank; Ye, Jing Yong; Myc, Andrzej; Thomas, Thommey; Cao, Zhengyi; Duran-Struuck, Raimon; Luker, Kathryn E; Luker, Gary D; Norris, Theodore B; Baker, James R

    2008-02-15

    To detect and quantify multiple distinct populations of cells circulating simultaneously in the blood of living animals, we developed a novel optical system for two-channel, two-photon flow cytometry in vivo. We used this system to investigate the circulation dynamics in live animals of breast cancer cells with low (MCF-7) and high (MDA-MB-435) metastatic potential, showing for the first time that two different populations of circulating cells can be quantified simultaneously in the vasculature of a single live mouse. We also non-invasively monitored a population of labeled, circulating red blood cells for more than two weeks, demonstrating that this technique can also quantify the dynamics of abundant cells in the vascular system for prolonged periods of time. These data are the first in vivo application of multichannel flow cytometry utilizing two-photon excitation, which will greatly enhance our capability to study circulating cells in cancer and other disease processes.

  5. A Mathematical Model of Baculovirus Infection on Insect Cells at Low Multiplicity of Infection

    Institute of Scientific and Technical Information of China (English)

    You-Hong ZHANG; Josée C. MERCHUK

    2004-01-01

    The expression efficiency of the insect cells-baculovirus system used for insecticidal virus production and the expression of medically useful foreign genes is closely related with the dynamics of infection. The present studies develop a model of the dynamic process of insect cell infection with baculovirus at low multiplicity of infection (MOI), which is based on the multi-infection cycles of insect cell infection at low MOI. A mathematical model for the amount of viruses released from primary infected cells and the amount of free viruses before secondary infected cells release viruses has been developed. Comparison of the simulation results with the experimental data confirms qualitatively that this model is highly reasonable before secondary infected cells release viruses. This model is considered as a base for further modeling the entire complicated infection process.

  6. Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Rodriguez Jorge

    2009-04-01

    Full Text Available Abstract The stromal vascular fraction (SVF of adipose tissue is known to contain mesenchymal stem cells (MSC, T regulatory cells, endothelial precursor cells, preadipocytes, as well as anti-inflammatory M2 macrophages. Safety of autologous adipose tissue implantation is supported by extensive use of this procedure in cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose derived MSC. Equine and canine studies demonstrating anti-inflammatory and regenerative effects of non-expanded SVF cells have yielded promising results. Although non-expanded SVF cells have been used successfully in accelerating healing of Crohn's fistulas, to our knowledge clinical use of these cells for systemic immune modulation has not been reported. In this communication we discuss the rationale for use of autologous SVF in treatment of multiple sclerosis and describe our experiences with three patients. Based on this rationale and initial experiences, we propose controlled trials of autologous SVF in various inflammatory conditions.

  7. Integration and Visualization of Multiple Sensors in Generating the NOAA Operational Snow and Ice Cover Products

    Science.gov (United States)

    Li, M.; Helfrich, S.

    2011-12-01

    Global snow and ice cover is a key component in the climate and hydrologic system as well as daily weather forecasting. The National Oceanic and Atmospheric Administration (NOAA) has produced a daily northern hemisphere snow and ice cover chart since 1997 through the Interactive Multisensor Snow and Ice Mapping System (IMS). The IMS integrates and visualizes a wide variety of satellite data, as well as derived snow/ice products and surface observations, to provide meteorologists with the ability to interactively prepare the daily northern hemisphere snow and ice cover chart. These products are presently used as operational inputs into several weather prediction models and are applied in climate monitoring. The IMS is currently on its second version (released in 2004) and scheduled to be upgraded to the third version (V3) in 2013. The IMS V3 will have nearly 40 external inputs as data sources processed by the IMS, which fall into five data formats: binary image, HDF file, GeoTIFF image, Shapefile image and ASCII file. With the exception of the GeoTIFF and Shapefile files, which are used directly by IMS, all other types of data are pre-processed to ENVI image file format and "sectorized" for different areas around the northern hemisphere. The IMS V3 will generate daily snow and ice cover maps in five formats: ASCII, ENVI, GeoTIFF, GIF and GRIB2 and three resolutions: 24km, 4km and 1km. In this presentation, the methods are discussed for accessing and processing satellite data, model results and surface reports. All input data with varying formats and resolutions are processed to a fixed projection. The visualization methodology for IMS are provided for five different resolutions of 48km, 24km, 8km, 4km, 2km and 1km. This work will facilitate the future enhancement of IMS, provide users with an understanding of the software architecture, provide a prospectus on future data sources, and help to preserve the integrity of the long-standing satellite-derived snow and ice

  8. A Model of Generating Visual Place Cells Based on Environment Perception and Similar Measure

    Science.gov (United States)

    2016-01-01

    It is an important content to generate visual place cells (VPCs) in the field of bioinspired navigation. By analyzing the firing characteristic of biological place cells and the existing methods for generating VPCs, a model of generating visual place cells based on environment perception and similar measure is abstracted in this paper. VPCs' generation process is divided into three phases, including environment perception, similar measure, and recruiting of a new place cell. According to this process, a specific method for generating VPCs is presented. External reference landmarks are obtained based on local invariant characteristics of image and a similar measure function is designed based on Euclidean distance and Gaussian function. Simulation validates the proposed method is available. The firing characteristic of the generated VPCs is similar to that of biological place cells, and VPCs' firing fields can be adjusted flexibly by changing the adjustment factor of firing field (AFFF) and firing rate's threshold (FRT). PMID:27597859

  9. A Model of Generating Visual Place Cells Based on Environment Perception and Similar Measure

    Directory of Open Access Journals (Sweden)

    Yang Zhou

    2016-01-01

    Full Text Available It is an important content to generate visual place cells (VPCs in the field of bioinspired navigation. By analyzing the firing characteristic of biological place cells and the existing methods for generating VPCs, a model of generating visual place cells based on environment perception and similar measure is abstracted in this paper. VPCs’ generation process is divided into three phases, including environment perception, similar measure, and recruiting of a new place cell. According to this process, a specific method for generating VPCs is presented. External reference landmarks are obtained based on local invariant characteristics of image and a similar measure function is designed based on Euclidean distance and Gaussian function. Simulation validates the proposed method is available. The firing characteristic of the generated VPCs is similar to that of biological place cells, and VPCs’ firing fields can be adjusted flexibly by changing the adjustment factor of firing field (AFFF and firing rate’s threshold (FRT.

  10. A Model of Generating Visual Place Cells Based on Environment Perception and Similar Measure.

    Science.gov (United States)

    Zhou, Yang; Wu, Dewei

    2016-01-01

    It is an important content to generate visual place cells (VPCs) in the field of bioinspired navigation. By analyzing the firing characteristic of biological place cells and the existing methods for generating VPCs, a model of generating visual place cells based on environment perception and similar measure is abstracted in this paper. VPCs' generation process is divided into three phases, including environment perception, similar measure, and recruiting of a new place cell. According to this process, a specific method for generating VPCs is presented. External reference landmarks are obtained based on local invariant characteristics of image and a similar measure function is designed based on Euclidean distance and Gaussian function. Simulation validates the proposed method is available. The firing characteristic of the generated VPCs is similar to that of biological place cells, and VPCs' firing fields can be adjusted flexibly by changing the adjustment factor of firing field (AFFF) and firing rate's threshold (FRT). PMID:27597859

  11. High Throughput Single-cell and Multiple-cell Micro-encapsulation

    OpenAIRE

    Lagus, Todd P.; Edd, Jon F.

    2012-01-01

    Microfluidic encapsulation methods have been previously utilized to capture cells in picoliter-scale aqueous, monodisperse drops, providing confinement from a bulk fluid environment with applications in high throughput screening, cytometry, and mass spectrometry. We describe a method to not only encapsulate single cells, but to repeatedly capture a set number of cells (here we demonstrate one- and two-cell encapsulation) to study both isolation and the interactions between cells in groups of ...

  12. Generation of cytotoxic T cell against HBcAg using retrovirally transduced dendritic cells

    Institute of Scientific and Technical Information of China (English)

    Chuan-Lin Ding; Kun Yao; Tian-Tai Zhang; Feng Zhou; Lin Xu; Jiang-Ying Xu

    2003-01-01

    AIM: Cytotoxic T lymphocytes (CTLs) play an important role in resolving HBV infection. In the present study, we attempted to evaluate the efficiency of bone marrow-derived dendritic cells (DCs) transduced with recombinant retroviral vector bearing hepatitis B virus (HBV) core gene and the capability of generating CTLs against HBcAg by genetically modified DCs in vivo.METHODS: A retroviral vector containing HBV core gene was constructed. Replicating DC progenitor of C57BL/6 mice was transduced by retroviral vector and continually cultured in the presence of recombinant mouse granulocytemacrophage colony-stimulating factor (rmGM-CSF) and interleukin-4(IL-4) for 6 days. LPS was added and cultured for additional two days. The efficiency of gene transfer was determined by PCR, Western blot and FACS. Transduced DCs immunized C57BL/6 mice subcutaneously 2 times at an oneweek interval. Intracellular IFN-γ and IL-4 of immunized mice lymphocytes were analyzed. Generation of CTLs in lymphooytes stimulated with mitomycin C-treated EL4-C cell which stably expresses HBcAg was determined by LDH release assays.RESULTS: Recombinant retroviral expression vector (pLCSN) was positively detected by PCR as well as enzyme digestion with EcoRI and BamH I. Retroviruses were generated by pLCSN transfection packing cell and the virus titer was 3x10s CFU/ml. Indirect immunofluorescence and FACS showed that HBV core gene was expressed in murine fibroblasts. Transduced bone marrow cells had capability of differentiating into DCsc in vitro in the presence of rmGMCSF and rmIL-4. The result of PCR showed that HBV core gene was integrated into the genome of transduced DCs.Western blot analysis showed that HBV core gene was expressed in DCs. The transduction rate was 28 % determined by FACS. Retroviral transduction had no influence on DCs expressions of CD80 and MHC class Ⅱ. HBcAg specific CTLs and Th1 type immune responses could be generated in the mice by using transduced DCs as antigen

  13. Amniotic Epithelial Cells from the Human Placenta Potently Suppress a Mouse Model of Multiple Sclerosis

    OpenAIRE

    Yu Han Liu; Vijesh Vaghjiani; Jing Yang Tee; Kelly To; Peng Cui; Ding Yuan Oh; Ursula Manuelpillai; Ban-Hock Toh; James Chan

    2012-01-01

    Human amniotic epithelial cells (hAEC) have stem cell-like features and immunomodulatory properties. Here we show that hAEC significantly suppressed splenocyte proliferation in vitro and potently attenuated a mouse model of multiple sclerosis (MS). Central nervous system (CNS) CD3(+) T cell and F4/80(+) monocyte/macrophage infiltration and demyelination were significantly reduced with hAEC treatment. Besides the known secretion of prostaglandin E2 (PGE2), we report the novel finding that hAEC...

  14. Chemokine receptor expression on B cells and effect of interferon-beta in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Roed, Hanne; Sellebjerg, Finn

    2002-01-01

    We investigated the B-cell expression of chemokine receptors CXCR3, CXCR5 and CCR5 in the blood and cerebrospinal fluid (CSF) from patients in relapse of multiple sclerosis (MS) and in neurological controls. Chemokine receptor expression was also studied in interferon-beta-treated patients...... with relapsing-remitting or secondary progressive MS. We observed significantly higher expression of CXCR3 on B cells in the CSF in active MS than in controls. Patients with active MS also had higher B-cell expression of CCR5 in blood. No major differences between RRMS and SPMS patients were detected...

  15. Successful generation of cloned mice using nuclear transfer from induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    Shuya Zhou; Chunjing Feng; Tang Hai; Liu Wang; Qi Zhou; Chenhui Ding; Xiaoyang Zhao; Eryao Wang; Xiangpeng Dai; Lei Liu; Wei Li; Zichuan Liu; Haifeng Wan

    2010-01-01

    Dear Editor, It is now well known that somatic cells can be efficiently reprogrammed into induced pluripotent stem cells (iPSCs) by forced expression of defined factors [1-3]. These cells, like embryonic stem cells (ESCs), have true pluripotency as shown by the live, fertile mice that can be generated through the tetraploid complementation assay using these iPSCs [4, 5].

  16. Apoptotic effects of non-edible parts of Punica granatum on human multiple myeloma cells.

    Science.gov (United States)

    Kiraz, Yağmur; Neergheen-Bhujun, Vidushi S; Rummun, Nawraj; Baran, Yusuf

    2016-02-01

    Multiple myeloma is of great concern since existing therapies are unable to cure this clinical condition. Alternative therapeutic approaches are mandatory, and the use of plant extracts is considered interesting. Punica granatum and its derived products were suggested as potential anticancer agents due to the presence of bioactive compounds. Thus, polypenolic-rich extracts of the non-edible parts of P. granatum were investigated for their antiproliferative and apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were dose-dependent decreases in the proliferation of U266 cells in response to P. granatum extracts. Also, exposure to the extracts triggered apoptosis with significant increases in loss of mitochondrial membrane potential in U266 cells exposed to the leaves and stem extracts, while the flower extract resulted in slight increases in loss of MMP. These results were confirmed by Annexin-V analysis. These results documented the cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells via disruption of mitochondrial membrane potential and increasing cell cycle arrest. The data suggest that the extracts can be envisaged in cancer chemoprevention and call for further exploration into the potential application of these plant parts. PMID:26318303

  17. Combining multiple models to generate consensus: Application to radiation-induced pneumonitis prediction

    International Nuclear Information System (INIS)

    The fusion of predictions from disparate models has been used in several fields to obtain a more realistic and robust estimate of the ''ground truth'' by allowing the models to reinforce each other when consensus exists, or, conversely, negate each other when there is no consensus. Fusion has been shown to be most effective when the models have some complementary strengths arising from different approaches. In this work, we fuse the results from four common but methodologically different nonlinear multivariate models (Decision Trees, Neural Networks, Support Vector Machines, Self-Organizing Maps) that were trained to predict radiation-induced pneumonitis risk on a database of 219 lung cancer patients treated with radiotherapy (34 with Grade 2+ postradiotherapy pneumonitis). Each model independently incorporated a small number of features from the available set of dose and nondose patient variables to predict pneumonitis; no two models had all features in common. Fusion was achieved by simple averaging of the predictions for each patient from all four models. Since a model's prediction for a patient can be dependent on the patient training set used to build the model, the average of several different predictions from each model was used in the fusion (predictions were made by repeatedly testing each patient with a model built from different cross-validation training sets that excluded the patient being tested). The area under the receiver operating characteristics curve for the fused cross-validated results was 0.79, with lower variance than the individual component models. From the fusion, five features were extracted as the consensus among all four models in predicting radiation pneumonitis. Arranged in order of importance, the features are (1) chemotherapy; (2) equivalent uniform dose (EUD) for exponent a=1.2 to 3; (3) EUD for a=0.5 to 1.2, lung volume receiving >20-30 Gy; (4) female sex; and (5) squamous cell histology. To facilitate ease of interpretation and

  18. Mantle Cell Lymphoma of Intestine Presenting as Multiple Lymphomatous Polyposis with Intussusception

    Directory of Open Access Journals (Sweden)

    Meena N. Jadhav

    2015-01-01

    Full Text Available Mantle Cell Lymphoma (MCL is a distinct clinicopathological subtype of B-cell non-Hodgkin's lymphoma (NHL accounting for 2-10% of all NHL cases. Gastrointestinal tract (GIT is the predominant site of extranodal MCL which commonly presents as Multiple Lymphomatous Polyposis (MLP. A 60 year old male presented with pain abdomen, diarrhea and weight loss of two months duration. On colonoscopy multiple polyps were found in the entire colon and rectum. Computed tomography revealed ileo-colic intussusception with nodularity in the lead point. Histopathology suggested features of MCL. On immunohistochemistry, the tumor cells were positive for CD20, CD5, Cyclin D1, negative for CD3, CD10, CD23, and CD45 RO

  19. Multiple scale model for cell migration in monolayers: Elastic mismatch between cells enhances motility.

    Science.gov (United States)

    Palmieri, Benoit; Bresler, Yony; Wirtz, Denis; Grant, Martin

    2015-01-01

    We propose a multiscale model for monolayer of motile cells that comprise normal and cancer cells. In the model, the two types of cells have identical properties except for their elasticity; cancer cells are softer and normal cells are stiffer. The goal is to isolate the role of elasticity mismatch on the migration potential of cancer cells in the absence of other contributions that are present in real cells. The methodology is based on a phase-field description where each cell is modeled as a highly-deformable self-propelled droplet. We simulated two types of nearly confluent monolayers. One contains a single cancer cell in a layer of normal cells and the other contains normal cells only. The simulation results demonstrate that elasticity mismatch alone is sufficient to increase the motility of the cancer cell significantly. Further, the trajectory of the cancer cell is decorated by several speed "bursts" where the cancer cell quickly relaxes from a largely deformed shape and consequently increases its translational motion. The increased motility and the amplitude and frequency of the bursts are in qualitative agreement with recent experiments. PMID:26134134

  20. Survival and Functionality of Human Induced Pluripotent Stem Cell-Derived Oligodendrocytes in a Nonhuman Primate Model for Multiple Sclerosis

    NARCIS (Netherlands)

    Thiruvalluvan, Arun; Czepiel, Marcin; Kap, Yolanda A; Mantingh-Otter, Ietje; Vainchtein, Ilia; Kuipers, Jeroen; Bijlard, Marjolein; Baron, Wia; Giepmans, Ben; Brück, Wolfgang; 't Hart, Bert A; Boddeke, Erik; Copray, Sjef

    2016-01-01

    : Fast remyelination by endogenous oligodendrocyte precursor cells (OPCs) is essential to prevent axonal and subsequent retrograde neuronal degeneration in demyelinating lesions in multiple sclerosis (MS). In chronic lesions, however, the remyelination capacity of OPCs becomes insufficient. Cell the

  1. The Contribution of Immune and Glial Cell Types in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Samuel S. Duffy

    2014-01-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory disease of the central nervous system characterised by widespread areas of focal demyelination. Its aetiology and pathogenesis remain unclear despite substantial insights gained through studies of animal models, most notably experimental autoimmune encephalomyelitis (EAE. MS is widely believed to be immune-mediated and pathologically attributable to myelin-specific autoreactive CD4+ T cells. In recent years, MS research has expanded beyond its focus on CD4+ T cells to recognise the contributions of multiple immune and glial cell types to the development, progression, and amelioration of the disease. This review summarises evidence of T and B lymphocyte, natural killer cell, macrophage/microglial, astrocytic, and oligodendroglial involvement in both EAE and MS and the intercommunication and influence of each cell subset in the inflammatory process. Despite important advances in the understanding of the involvement of these cell types in MS, many questions still remain regarding the various subsets within each cell population and their exact contribution to different stages of the disease.

  2. Next generation sequencing (NGS) database for tandem repeats with multiple pattern 2°-shaft multicore string matching.

    Science.gov (United States)

    Someswara Rao, Chinta; Raju, S Viswanadha

    2016-03-01

    Next generation sequencing (NGS) technologies have been rapidly applied in biomedical and biological research in recent years. To provide the comprehensive NGS resource for the research, in this paper , we have considered 10 loci/codi/repeats TAGA, TCAT, GAAT, AGAT, AGAA, GATA, TATC, CTTT, TCTG and TCTA. Then we developed the NGS Tandem Repeat Database (TandemRepeatDB) for all the chromosomes of Homo sapiens, Callithrix jacchus, Chlorocebus sabaeus, Gorilla gorilla, Macaca fascicularis, Macaca mulatta, Nomascus leucogenys, Pan troglodytes, Papio anubis and Pongo abelii genome data sets for all those locis. We find the successive occurence frequency for all the above 10 SSR (simple sequence repeats) in the above genome data sets on a chromosome-by-chromosome basis with multiple pattern 2° shaft multicore string matching.

  3. Multiple target implementation for a doubly fed induction generator based on direct power control under unbalanced and distorted grid voltage

    Institute of Scientific and Technical Information of China (English)

    Heng NIAN; Yi-peng SONG

    2015-01-01

    This paper presents a multiple target implementation technique for a doubly fed induction generator (DFIG) under unbalanced and distorted grid voltage based on direct power control (DPC). Based on the mathematical model of DFIG under unbalanced and distorted voltage, the proportional and integral (PI) regulator is adopted to regulate the DFIG average active and reactive powers, while the vector PI (VPI) resonant regulator is used to achieve three alternative control targets: (1) balanced and sinusoidal stator current; (2) smooth instantaneous stator active and reactive powers; (3) smooth electromagnetic torque and instantaneous stator reactive power. The major advantage of the proposed control strategy over the conventional method is that neither negative and harmonic sequence decomposition of grid voltage nor complicated control reference calculation is required. The insensitivity of the proposed control strategy to DFIG parameter deviation is analyzed. Finally, the DFIG experimental system is developed to validate the availability of the proposed DPC strategy under unbalanced and distorted grid voltage.

  4. Next generation sequencing (NGS) database for tandem repeats with multiple pattern 2°-shaft multicore string matching

    Science.gov (United States)

    Someswara Rao, Chinta; Raju, S. Viswanadha

    2016-01-01

    Next generation sequencing (NGS) technologies have been rapidly applied in biomedical and biological research in recent years. To provide the comprehensive NGS resource for the research, in this paper , we have considered 10 loci/codi/repeats TAGA, TCAT, GAAT, AGAT, AGAA, GATA, TATC, CTTT, TCTG and TCTA. Then we developed the NGS Tandem Repeat Database (TandemRepeatDB) for all the chromosomes of Homo sapiens, Callithrix jacchus, Chlorocebus sabaeus, Gorilla gorilla, Macaca fascicularis, Macaca mulatta, Nomascus leucogenys, Pan troglodytes, Papio anubis and Pongo abelii genome data sets for all those locis. We find the successive occurence frequency for all the above 10 SSR (simple sequence repeats) in the above genome data sets on a chromosome-by-chromosome basis with multiple pattern 2° shaft multicore string matching. PMID:26981434

  5. Next generation sequencing (NGS) database for tandem repeats with multiple pattern 2°-shaft multicore string matching.

    Science.gov (United States)

    Someswara Rao, Chinta; Raju, S Viswanadha

    2016-03-01

    Next generation sequencing (NGS) technologies have been rapidly applied in biomedical and biological research in recent years. To provide the comprehensive NGS resource for the research, in this paper , we have considered 10 loci/codi/repeats TAGA, TCAT, GAAT, AGAT, AGAA, GATA, TATC, CTTT, TCTG and TCTA. Then we developed the NGS Tandem Repeat Database (TandemRepeatDB) for all the chromosomes of Homo sapiens, Callithrix jacchus, Chlorocebus sabaeus, Gorilla gorilla, Macaca fascicularis, Macaca mulatta, Nomascus leucogenys, Pan troglodytes, Papio anubis and Pongo abelii genome data sets for all those locis. We find the successive occurence frequency for all the above 10 SSR (simple sequence repeats) in the above genome data sets on a chromosome-by-chromosome basis with multiple pattern 2° shaft multicore string matching. PMID:26981434

  6. Peptide-beta2-microglobulin-major histocompatibility complex expressing cells are potent antigen-presenting cells that can generate specific T cells.

    Science.gov (United States)

    Obermann, Sonja; Petrykowska, Susanne; Manns, Michael P; Korangy, Firouzeh; Greten, Tim F

    2007-09-01

    Adoptive T-cell therapy represents a promising therapeutic approach for the treatment of cancer. Successful adoptive immunotherapy depends on the ex vivo priming and expansion of antigen-specific T cells. However, the in vitro generation of adequate numbers of functional antigen-specific T cell remains a major obstacle. It is important to develop efficient and reproducible methods to generate high numbers of antigen-specific T cells for adoptive T-cell transfer. We have developed a new artificial antigen-presenting cell (aAPC) by transfection of major histocompatibility (MHC) class I negative Daudi cells with a peptide-beta2-microglobulin-MHC fusion construct (single-chain aAPC) ensuring presentation of the peptide-MHC complex of interest. Using this artificial antigen-presenting cell, we could generate up to 9.2 x 10(8) antigen-specific cytotoxic CD8(+) T cells from 10 ml blood. In vitro generated T cells lysed endogenously presented antigens. Direct comparison of the single-chain aAPC with autologous monocyte-derived dendritic cells demonstrated that these cells were equally efficient in stimulation of T cells. Finally, we were able to generate antigen-specific T cell lines from perpheral blood mononuclear cells of patients receiving cytotoxic chemotherapy. The use of single-chain aAPC represent a promising option for the generation of antigen-specific CD8(+) T cells, which could be used for adoptive T-cell therapy.

  7. Peptide-β2-microglobulin-major histocompatibility complex expressing cells are potent antigen-presenting cells that can generate specific T cells

    Science.gov (United States)

    Obermann, Sonja; Petrykowska, Susanne; Manns, Michael P; Korangy, Firouzeh; Greten, Tim F

    2007-01-01

    Adoptive T-cell therapy represents a promising therapeutic approach for the treatment of cancer. Successful adoptive immunotherapy depends on the ex vivo priming and expansion of antigen-specific T cells. However, the in vitro generation of adequate numbers of functional antigen-specific T cell remains a major obstacle. It is important to develop efficient and reproducible methods to generate high numbers of antigen-specific T cells for adoptive T-cell transfer. We have developed a new artificial antigen-presenting cell (aAPC) by transfection of major histocompatibility (MHC) class I negative Daudi cells with a peptide-β2-microglobulin–MHC fusion construct (single-chain aAPC) ensuring presentation of the peptide–MHC complex of interest. Using this artificial antigen-presenting cell, we could generate up to 9·2 × 108 antigen-specific cytotoxic CD8+ T cells from 10 ml blood. In vitro generated T cells lysed endogenously presented antigens. Direct comparison of the single-chain aAPC with autologous monocyte-derived dendritic cells demonstrated that these cells were equally efficient in stimulation of T cells. Finally, we were able to generate antigen-specific T cell lines from perpheral blood mononuclear cells of patients receiving cytotoxic chemotherapy. The use of single-chain aAPC represent a promising option for the generation of antigen-specific CD8+ T cells, which could be used for adoptive T-cell therapy. PMID:17472719

  8. Generation of mast cells from mouse fetus: analysis of differentiation and functionality, and transcriptome profiling using next generation sequencer.

    Directory of Open Access Journals (Sweden)

    Nobuyuki Fukuishi

    Full Text Available While gene knockout technology can reveal the roles of proteins in cellular functions, including in mast cells, fetal death due to gene manipulation frequently interrupts experimental analysis. We generated mast cells from mouse fetal liver (FLMC, and compared the fundamental functions of FLMC with those of bone marrow-derived mouse mast cells (BMMC. Under electron microscopy, numerous small and electron-dense granules were observed in FLMC. In FLMC, the expression levels of a subunit of the FcεRI receptor and degranulation by IgE cross-linking were comparable with BMMC. By flow cytometry we observed surface expression of c-Kit prior to that of FcεRI on FLMC, although on BMMC the expression of c-Kit came after FcεRI. The surface expression levels of Sca-1 and c-Kit, a marker of putative mast cell precursors, were slightly different between bone marrow cells and fetal liver cells, suggesting that differentiation stage or cell type are not necessarily equivalent between both lineages. Moreover, this indicates that phenotypically similar mast cells may not have undergone an identical process of differentiation. By comprehensive analysis using the next generation sequencer, the same frequency of gene expression was observed for 98.6% of all transcripts in both cell types. These results indicate that FLMC could represent a new and useful tool for exploring mast cell differentiation, and may help to elucidate the roles of individual proteins in the function of mast cells where gene manipulation can induce embryonic lethality in the mid to late stages of pregnancy.

  9. The emerging multiple metal nanostructures for enhancing the light trapping of thin film organic photovoltaic cells.

    Science.gov (United States)

    Choy, Wallace C H

    2014-10-18

    Recently, various metal nanostructures have been introduced into organic solar cells (OSCs) for performance enhancement. Here, we review the recent progress in OSCs incorporated with multiple metal nanostructures including various metal nanopatterns and metal nanomaterials. Multiple physical effects arise from these incorporated nanostructures, which require careful distinction. Changes induced by the metal nanostructures are examined in detail from the optical and electrical aspects. With the comprehensive understanding of the physical mechanisms for various metal nanostructures, further improvement in device performance and emerging applications can be expected for the new class of nanostructure-incorporated OSCs.

  10. Stem Cell Physics. Multiple-Laser-Beam Treatment of Parkinson's Disease

    Science.gov (United States)

    Stefan, V.

    2013-03-01

    A novel method for the treatment of Parkinson's disease is proposed. Pluripotent stem cells are laser cultured, using ultrashort wavelength, (around 0.1 micron-ultraviolet radiation-with intensities of a few mW/cm2) , multiple laser beams.[2] The multiple-energy laser photons[3] interact with the neuron DNA molecules to be cloned. The laser created dopaminergic substantia nigra neurons can be, (theoretically), laser transplanted, (a higher focusing precision as compared to a syringe method), into the striatum or substantia nigra regions of the brain, or both. Supported by Nikola Tesla Labs, Stefan University.

  11. Cellular interactions via conditioned media induce in vivo nephron generation from tubular epithelial cells or mesenchymal stem cells

    International Nuclear Information System (INIS)

    Highlights: •We have attempted in vivo nephron generation using conditioned media. •Vascular and tubular cells do cross-talks on cell proliferation and tubular changes. •Tubular cells suppress these changes in mesenchymal stem cells. •Tubular cells differentiate mesenchymal stem cells into tubular cells. •Nephrons can be created from implanted tubular cells or mesenchymal stem cells. -- Abstract: There are some successful reports of kidney generation by utilizing the natural course of kidney development, namely, the use of an artificially treated metanephros, blastocyst or ureteric bud. Under a novel concept of cellular interactions via conditioned media (CMs), we have attempted in vivo nephron generation from tubular epithelial cells (TECs) or mesenchymal stem cells (MSCs). Here we used 10× CMs of vascular endothelial cells (VECs) and TECs, which is the first to introduce a CM into the field of organ regeneration. We first present stimulative cross-talks induced by these CMs between VECs and TECs on cell proliferation and morphological changes. In MSCs, TEC-CM suppressed these changes, however, induced cytokeratin expression, indicating the differentiation of MSCs into TECs. As a result, glomerular and tubular structures were created following the implantation of TECs or MSCs with both CMs. Our findings suggest that the cellular interactions via CMs might induce in vivo nephron generation from TECs or MSCs. As a promoting factor, CMs could also be applied to the regeneration of other organs and tissues

  12. Cellular interactions via conditioned media induce in vivo nephron generation from tubular epithelial cells or mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Machiguchi, Toshihiko, E-mail: machiguchi.toshihiko.23u@st.kyoto-u.ac.jp; Nakamura, Tatsuo, E-mail: nakamura@frontier.kyoto-u.ac.jp

    2013-06-07

    Highlights: •We have attempted in vivo nephron generation using conditioned media. •Vascular and tubular cells do cross-talks on cell proliferation and tubular changes. •Tubular cells suppress these changes in mesenchymal stem cells. •Tubular cells differentiate mesenchymal stem cells into tubular cells. •Nephrons can be created from implanted tubular cells or mesenchymal stem cells. -- Abstract: There are some successful reports of kidney generation by utilizing the natural course of kidney development, namely, the use of an artificially treated metanephros, blastocyst or ureteric bud. Under a novel concept of cellular interactions via conditioned media (CMs), we have attempted in vivo nephron generation from tubular epithelial cells (TECs) or mesenchymal stem cells (MSCs). Here we used 10× CMs of vascular endothelial cells (VECs) and TECs, which is the first to introduce a CM into the field of organ regeneration. We first present stimulative cross-talks induced by these CMs between VECs and TECs on cell proliferation and morphological changes. In MSCs, TEC-CM suppressed these changes, however, induced cytokeratin expression, indicating the differentiation of MSCs into TECs. As a result, glomerular and tubular structures were created following the implantation of TECs or MSCs with both CMs. Our findings suggest that the cellular interactions via CMs might induce in vivo nephron generation from TECs or MSCs. As a promoting factor, CMs could also be applied to the regeneration of other organs and tissues.

  13. Human antigen-specific regulatory T cells generated by T cell receptor gene transfer.

    Directory of Open Access Journals (Sweden)

    Todd M Brusko

    Full Text Available BACKGROUND: Therapies directed at augmenting regulatory T cell (Treg activities in vivo as a systemic treatment for autoimmune disorders and transplantation may be associated with significant off-target effects, including a generalized immunosuppression that may compromise beneficial immune responses to infections and cancer cells. Adoptive cellular therapies using purified expanded Tregs represents an attractive alternative to systemic treatments, with results from animal studies noting increased therapeutic potency of antigen-specific Tregs over polyclonal populations. However, current methodologies are limited in terms of the capacity to isolate and expand a sufficient quantity of endogenous antigen-specific Tregs for therapeutic intervention. Moreover, FOXP3+ Tregs fall largely within the CD4+ T cell subset and are thus routinely MHC class II-specific, whereas class I-specific Tregs may function optimally in vivo by facilitating direct tissue recognition. METHODOLOGY/PRINCIPAL FINDINGS: To overcome these limitations, we have developed a novel means for generating large numbers of antigen-specific Tregs involving lentiviral T cell receptor (TCR gene transfer into in vitro expanded polyclonal natural Treg populations. Tregs redirected with a high-avidity class I-specific TCR were capable of recognizing the melanoma antigen tyrosinase in the context of HLA-A*0201 and could be further enriched during the expansion process by antigen-specific reactivation with peptide loaded artificial antigen presenting cells. These in vitro expanded Tregs continued to express FOXP3 and functional TCRs, and maintained the capacity to suppress conventional T cell responses directed against tyrosinase, as well as bystander T cell responses. Using this methodology in a model tumor system, murine Tregs designed to express the tyrosinase TCR effectively blocked antigen-specific effector T cell (Teff activity as determined by tumor cell growth and luciferase reporter

  14. CALCULUS FROM THE PAST: MULTIPLE DELAY SYSTEMS ARISING IN CANCER CELL MODELLING

    KAUST Repository

    WAKE, G. C.

    2013-01-01

    Nonlocal calculus is often overlooked in the mathematics curriculum. In this paper we present an interesting new class of nonlocal problems that arise from modelling the growth and division of cells, especially cancer cells, as they progress through the cell cycle. The cellular biomass is assumed to be unstructured in size or position, and its evolution governed by a time-dependent system of ordinary differential equations with multiple time delays. The system is linear and taken to be autonomous. As a result, it is possible to reduce its solution to that of a nonlinear matrix eigenvalue problem. This method is illustrated by considering case studies, including a model of the cell cycle developed recently by Simms, Bean and Koeber. The paper concludes by explaining how asymptotic expressions for the distribution of cells across the compartments can be determined and used to assess the impact of different chemotherapeutic agents. Copyright © 2013 Australian Mathematical Society.

  15. Inhibitory effect of mimosine on proliferation of human lung cancer cells is mediated by multiple mechanisms.

    Science.gov (United States)

    Chang, H C; Lee, T H; Chuang, L Y; Yen, M H; Hung, W C

    1999-10-18

    The plant amino acid mimosine has been reported to block cell cycle progression in the late G1 phase. A recent study showed that mimosine might induce growth arrest by activating the expression of p21CIP1, a cyclin-dependent kinase inhibitor (CDKI), and by inhibiting the activity of cyclin E-associated kinases in human breast cancer cells. However, mimosine at higher concentrations also blocked proliferation of p21-/- cells by unknown mechanisms. In this study, we investigated the effect of mimosine on the expression of cyclins and CDKIs in human lung cancer cells. We found that mimosine specifically inhibited cyclin D1 expression in H226 cells. The expression of another G1 cyclin, cyclin E, was not regulated by mimosine in all lung cancer cell lines examined. Moreover, mimosine induced p21CIP1 expression in H226 and H358 cells, while it activated p27KIP1 expression in H322 cells. However, mimosine does not affect transcription of these genes directly because significant changes in cyclin D1 or CDKI expression were observed at 12-24 h after drug addition. Our results indicate that mimosine may block cell proliferation by multiple mechanisms and this amino acid is a useful agent for the study of cell cycle control. PMID:10530763

  16. Plasma cell maturity as a predictor of prognosis in multiple myeloma.

    Science.gov (United States)

    Iriyama, Noriyoshi; Miura, Katsuhiro; Hatta, Yoshihiro; Uchino, Yoshihito; Kurita, Daisuke; Takahashi, Hiromichi; Sakagami, Hitomi; Sakagami, Masashi; Kobayashi, Yujin; Nakagawa, Masaru; Ohtake, Shimon; Iizuka, Yoshikazu; Takei, Masami

    2016-08-01

    In this study, the impact of plasma cell maturity on the prognoses of multiple myeloma (MM) patients in the era of novel agents was investigated. Myeloma cell maturity was classified via immunophenotyping: myeloma cells showing mature plasma cell 1 (MPC-1)-positive and CD49e-positive cells were considered mature type; MPC-1-positive and CD49e-negative cells were considered intermediate type; and MPC-1-negative cells were considered immature type. This study included 87 newly diagnosed MM patients who were initially treated with bortezomib and/or chemotherapy. Myeloma cell maturity was a critical factor affecting overall survival (OS) in the cohort, with median OS not reached in mature-type, 50 months in intermediate-type, and 20 months in immature-type cells. Multivariate analysis showed that immature type and stage III according to the International Staging System were both independent prognostic factors affecting OS. The findings of this study demonstrate the clinical importance of myeloma cell classification according to immunophenotyping using MPC-1 and CD49e antibodies to determine patient prognosis in this era of novel therapeutic agents. PMID:27383407

  17. Comparison of three transposons for the generation of highly productive recombinant CHO cell pools and cell lines.

    Science.gov (United States)

    Balasubramanian, Sowmya; Rajendra, Yashas; Baldi, Lucia; Hacker, David L; Wurm, Florian M

    2016-06-01

    Several naturally occurring vertebrate transposable elements have been genetically modified to enable the transposition of recombinant genes in mammalian cells. We compared three transposons-piggyBac, Tol2, and Sleeping Beauty-for their ability to generate cell pools (polyclonal cultures of recombinant cells) and clonal cell lines for the large-scale production of recombinant proteins using Chinese hamster ovary cells (CHO-DG44) as the host. Transfection with each of the dual-vector transposon systems resulted in cell pools with volumetric yields of tumor necrosis factor receptor-Fc fusion protein (TNFR:Fc) that were about ninefold higher than those from cell pools generated by conventional plasmid transfection. On average, the cell pools had 10-12 integrated copies of the transgene per cell. In the absence of selection, the volumetric productivity of the cell pools decreased by 50% over a 2-month cultivation period and then remained constant. The average volumetric TNFR:Fc productivity of clonal cell lines recovered from cell pools was about 25 times higher than that of cell lines generated by conventional transfection. In 14-day fed-batch cultures, TNFR:Fc levels up to 900 mg/L were obtained from polyclonal cell pools and up to 1.5 g/L from clonal cell lines using any of the three transposons. Biotechnol. Bioeng. 2016;113: 1234-1243. © 2015 Wiley Periodicals, Inc. PMID:26616356

  18. A novel and simple method for the generation of functional human dendritic cells from unfractionated peripheral blood mononuclear cells within 2 days: its application for induction of HIV-1-reactive CD4+ T cells in the hu-PBL SCID mice

    OpenAIRE

    Akira eKodama; Reiko eTanaka; Mineki eSaito; Ansari, Aftab A.; Yuetsu eTanaka

    2013-01-01

    Because dendritic cells (DCs) play a critical role in the regulation of adaptive immune responses, they have been ideal candidates for cell-based immunotherapy of cancers and infections in humans. Generally, monocyte-derived DCs (MDDCs) were generated from purified monocytes by multiple steps of time-consuming physical manipulations for an extended period cultivation. In this study, we developed a novel, simple and rapid method for the generation of type-1 helper T cell (Th1)-stimulating huma...

  19. Autoantigen-specific immunosuppression with tolerogenic peripheral blood cells prevents relapses in a mouse model of relapsing-remitting multiple sclerosis

    OpenAIRE

    Kleist, Christian; MOHR, ELISABETH; Gaikwad, Sadanand; Dittmar, Laura; Kuerten, Stefanie; Platten, Michael; Mier, Walter; Schmitt, Michael; Opelz, Gerhard; Terneß, Peter

    2016-01-01

    Background: Dendritic cells (DCs) rendered suppressive by treatment with mitomycin C and loaded with the autoantigen myelin basic protein demonstrated earlier their ability to prevent experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis (MS). This provides an approach for prophylactic vaccination against autoimmune diseases. For clinical application such DCs are difficult to generate and autoantigens hold the risk of exacerbating the disease. Methods: We ...

  20. Oleocanthal inhibits proliferation and MIP-1α expression in human multiple myeloma cells.

    Science.gov (United States)

    Scotece, M; Gómez, R; Conde, J; Lopez, V; Gómez-Reino, J J; Lago, F; Smith, A B; Gualillo, O

    2013-01-01

    Multiple myeloma (MM) is a plasma cell malignancy that causes devastating bone destruction by activating osteoclasts in the bone marrow milieu. MM is the second of all hematological malignancies. Thus, the search for new pharmacological weapons is under intensive investigation being MM a critically important public health goal. Recently, it has been demonstrated that macrophage inflammatory protein 1- alpha (MIP-1 α) is crucially involved in the development of osteolytic bone lesions in MM. Phenolic components of extra virgin olive oil are reported to have anti tumor activity. However, the underlying mechanisms and specific targets of extra virgin olive oil remain to be elucidated. In the present study, we investigated the effects of a recently isolated novel extra virgin olive oil polyphenol, oleocanthal, on the human multiple myeloma cell line ARH-77. Here we report that this natural compound has a remarkable in vitro activity by inhibiting MIP-1 α expression and secretion in MM cells. In addition, we also demonstrated that oleocanthal inhibits MM cells proliferation by inducing the activation of apoptosis mechanisms and by down-regulating ERK1/2 and AKT signal transduction pathways. This in vitro study suggests a therapeutic potential of oleocanthal in treating multiple myeloma. PMID:23521677

  1. Multiple metastases to the small bowel from large cell bronchial carcinomas

    Institute of Scientific and Technical Information of China (English)

    Davor Tomas; Mario Ledinsky; Mladen Belicza; Bozo Kru(s)lin

    2005-01-01

    AIM: Metastases from lung cancer to gastrointestinal tract are not rare atpostmortem studies but the development of clinically significant symptoms from the gastrointestinal metastases is very unusual.METHODS: Formalin-fixed, paraffin-embedded tissues were cut into 5 μm thick sections and routinely stained with hematoxylin and eosin. Some slides were also stained with Alcian-PAS. Antibodies used were primary antibodies to pancytokeratin, cytokeratin 7, cytokeratin 20, epithelial membrane antigen, vimentin, smooth muscle actin and CD-117.RESULTS: We observed three patients who presented with multiple metastases from large cell bronchial carcinoma to small intestine. Two of them had abdominal symptoms (sudden onset of abdominal pain, constipation and vomiting) and in one case the tumor was incidentally found during autopsy. Microscopically, all tumors showed a same histological pattern and consisted almost exclusively of strands and sheets of poorly cohesive, polymorphic giant cells with scanty, delicate stromas. Few smaller polygonal anaplastic cells dispersed between polymorphic giant cells,were also observed. Immunohistochemistry showed positive staining of the tumor cells with cytokeratin and vimentin. Microscopically and immunohistochemically all metastases had a similar pattern to primary anaplastic carcinoma of the small intestine.CONCLUSION: In patients with small intestine tumors showing anaplastic features, especially with multiple tumors, metastases from large cell bronchial carcinoma should be first excluded, because it seems that they are more common than expected.

  2. Andrographolide inhibits multiple myeloma cells by inhibiting the TLR4/NF-κB signaling pathway.

    Science.gov (United States)

    Gao, Hui; Wang, Jianrong

    2016-02-01

    Andrographolide is an active component from the extract of Andrographis paniculata [(Burm.f) Nees], a medicinal plant from the Acanthaceae family. Pharmacological studies have revealed that andrographolide possesses anti-bacterial, anti-inflammatory, anti-viral, immune regulatory and hepatoprotective properties, and is efficacious in the treatment of cardiovascular diseases, while exhibiting low toxicity and low cost. The present study aimed to determine the inhibitory effects of andrographolide on the growth of multiple myeloma (MM) cells and its possible impact on the Toll-like receptor (TLR)4/nuclear factor (NF)-κB signaling pathway. Cell proliferation was detected using an MTT assay, cellular apoptosis was measured using flow cytometry, and caspase-9/3 activation were assessed using colorimetric assay kits. Furthermore, TLR4 and NF-κB protein expression was determined by western blot analysis. The results revealed that andrographolide reduced the proliferation, while increasing cellular apoptosis and caspase-9/3 activation of MM cells, in addition to downregulating the expression of TLR4 and NF-κB protein. Of note, TLR4- or NF-κB-targeting small-interfering (si)RNA enhanced the andrographolide-induced inhibition of cell proliferation and induction of apoptosis of MM cells. The results of the present study therefore suggested that andrographolide inhibited multiple myeloma cells via the TLR4/NF-κB signaling pathway. PMID:26707811

  3. Induction of Cancer Cell Death by Isoflavone: The Role of Multiple Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Fazlul H. Sarkar

    2011-10-01

    Full Text Available Soy isoflavones have been documented as dietary nutrients broadly classified as “natural agents” which plays important roles in reducing the incidence of hormone-related cancers in Asian countries, and have shown inhibitory effects on cancer development and progression in vitro and in vivo, suggesting the cancer preventive or therapeutic activity of soy isoflavones against cancers. Emerging experimental evidence shows that isoflavones could induce cancer cell death by regulating multiple cellular signaling pathways including Akt, NF-κB, MAPK, Wnt, androgen receptor (AR, p53 and Notch signaling, all of which have been found to be deregulated in cancer cells. Therefore, homeostatic regulation of these important cellular signaling pathways by isoflavones could be useful for the activation of cell death signaling, which could result in the induction of apoptosis of both pre-cancerous and/or cancerous cells without affecting normal cells. In this article, we have attempted to summarize the current state-of-our-knowledge regarding the induction of cancer cell death pathways by isoflavones, which is believed to be mediated through the regulation of multiple cellular signaling pathways. The knowledge gained from this article will provide a comprehensive view on the molecular mechanism(s by which soy isoflavones may exert their effects on the prevention of tumor progression and/or treatment of human malignancies, which would also aid in stimulating further in-depth mechanistic research and foster the initiation of novel clinical trials.

  4. Activation of multiple apoptotic pathways in human nasopharyngeal carcinoma cells by the prenylated isoflavone, osajin.

    Directory of Open Access Journals (Sweden)

    Tsung-Teng Huang

    Full Text Available Osajin is a prenylated isoflavone showing antitumor activity in different tumor cell lines. The underlying mechanism of osajin-induced cancer cell death is not clearly understood. In the present study, the mechanisms of osajin-induced cell death of human nasopharyngeal carcinoma (NPC cells were explored. Osajin was found to significantly induce apoptosis of NPC cells in a dose- and time-dependent manner. Multiple molecular effects were observed during osajin treatment including a significant loss of mitochondrial transmembrane potential, release of cytochrome c into the cytosol, enhanced expression of Fas ligand (FasL, suppression of glucose-regulated protein 78 kDa (GRP78, and activation of caspases-9, -8, -4 and -3. In addition, up-regulation of proapoptotic Bax protein and down-regulation of antiapoptotic Bcl-2 protein were also observed. Taken together, osajin induces apoptosis in human NPC cells through multiple apoptotic pathways, including the extrinsic death receptor pathway, and intrinsic pathways relying on mitochondria and endoplasmic reticulum stress. Thus, osajin could be developed as a new effective and chemopreventive compound for human NPC.

  5. Generation of induced pluripotent stem cells from the pig

    Science.gov (United States)

    The value of stem cells has become increasingly evident in recent years with the advent of genetic engineering tools that allow site-specific modifications to the genome. The use of stem cells to induce modifications has several potential benefits for the livestock industry including improving anim...

  6. Multiple-octave spanning high-energy mid-IR supercontinuum generation in bulk quadratic nonlinear crystals

    DEFF Research Database (Denmark)

    Zhou, Binbin; Bache, Morten

    2016-01-01

    Bright and broadband coherent mid-IR radiation is important for exciting and probing molecular vibrations. Using cascaded nonlinearities in conventional quadratic nonlinear crystals like lithium niobate, self-defocusing near-IR solitons have been demonstrated that led to very broadband superconti......Bright and broadband coherent mid-IR radiation is important for exciting and probing molecular vibrations. Using cascaded nonlinearities in conventional quadratic nonlinear crystals like lithium niobate, self-defocusing near-IR solitons have been demonstrated that led to very broadband...... supercontinuum generation in the visible, near-IR, and short-wavelength mid-IR. Here we conduct an experiment where a mid-IR crystal is pumped in the mid-IR. The crystal is cut for noncritical interaction, so the three-wave mixing of a single mid-IR femtosecond pump source leads to highly phase-mismatched second......-harmonic generation. This self-acting cascaded process leads to the formation of a self-defocusing soliton at the mid-IR pump wavelength and after the self-compression point multiple octave-spanning supercontinua are observed. The results were recorded in a commercially available crystal LiInS2 pumped in the 3-4 µm...

  7. Invited Article: Multiple-octave spanning high-energy mid-IR supercontinuum generation in bulk quadratic nonlinear crystals

    Science.gov (United States)

    Zhou, Binbin; Bache, Morten

    2016-08-01

    Bright and broadband coherent mid-IR radiation is important for exciting and probing molecular vibrations. Using cascaded nonlinearities in conventional quadratic nonlinear crystals like lithium niobate, self-defocusing near-IR solitons have been demonstrated that led to very broadband supercontinuum generation in the visible, near-IR, and short-wavelength mid-IR. Here we conduct an experiment where a mid-IR crystal is pumped in the mid-IR. The crystal is cut for noncritical interaction, so the three-wave mixing of a single mid-IR femtosecond pump source leads to highly phase-mismatched second-harmonic generation. This self-acting cascaded process leads to the formation of a self-defocusing soliton at the mid-IR pump wavelength and after the self-compression point multiple octave-spanning supercontinua are observed. The results were recorded in a commercially available crystal LiInS2 pumped in the 3-4 μm range with 85 fs 50 μJ pulse energy, with the broadest supercontinuum covering 1.6-7.0 μm. We measured up 30 μJ energy in the supercontinuum, and the energy promises to scale favorably with an increased pump energy. Other mid-IR crystals can readily be used as well to cover other pump wavelengths and target other supercontinuum wavelength ranges.

  8. Monolithic fuel cell based power source for burst power generation

    Science.gov (United States)

    Fee, D. C.; Blackburn, P. E.; Busch, D. E.; Dees, D. W.; Dusek, J.; Easler, T. E.; Ellingson, W. A.; Flandermeyer, B. K.; Fousek, R. J.; Heiberger, J. J.

    A unique fuel cell coupled with a low power nuclear reactor presents an attractive approach for SDI burst power requirements. The monolithic fuel cell looks attractive for space applications and represents a quantum jump in fuel cell technology. Such a breakthrough in design is the enabling technology for lightweight, low volume power sources for space based pulse power systems. The monolith is unique among fuel cells in being an all solid state device. The capability for miniaturization, inherent in solid state devices, gives the low volume required for space missions. In addition, the solid oxide fuel cell technology employed in the monolith has high temperature reject heat and can be operated in either closed or open cycles. Both these features are attractive for integration into a burst power system.

  9. Generation and application of human iPS cells

    Institute of Scientific and Technical Information of China (English)

    CUI Ghun; RAO LingJun; CHENG LinZhao; XIAO Lei

    2009-01-01

    Human embryonic stem (ES) cells are capable of unlimited proliferation and maintenance of pluripo-tency in vitro; these properties may lead to potential applications in regenerative medicine.However,immune rejection hampers the allogenic application of human ES cells.Over-expression of several specific transcription factors has been used to reprogram human adult cells into induced pluripotent stem (iPS) cells,which are similar to hESCs in many aspects.The iPS technique makes it possible to produce patient-specific pluripotent stem cells for transplantation therapy without immune rejection.However,some challenges remain,including viral vector integration into the genome,the existence of exogenous oncogenic factors,and low induction efficiency.Here,we review recent advances in human iPS methodology,as well as remaining challenges and its potential applications.

  10. Generation and Regulation of CD8+ Regulatory T Cells

    Institute of Scientific and Technical Information of China (English)

    Linrong Lu; Harvey Cantor

    2008-01-01

    Research into the suppressive activity of CD4+FoxP3+ T regulatory cells (Treg) has defined a sublineage of CD4+ cells that contribute to self-tolerance and resistance to autoimmune disease. Much less attention has been given to the potential contribution of regulatory sublineages of CD8+ cells. Analysis of a small fraction of CD8+ cells that target autoreactive CD4+ cells through recognition of the MHC class Ib molecule Qa-1 in mouse and HLA-E in human has revitalized interest in CD8+ Treg. Here we summarize recent progress and future directions of research into the role of this CD8+ sublineage in resistance to autoimmune disease. Cellular & Molecular Immunology. 2008;5(6):401-406.

  11. Generation of ESC-derived Mouse Airway Epithelial Cells Using Decellularized Lung Scaffolds.

    Science.gov (United States)

    Shojaie, Sharareh; Lee, Joyce; Wang, Jinxia; Ackerley, Cameron; Post, Martin

    2016-01-01

    Lung lineage differentiation requires integration of complex environmental cues that include growth factor signaling, cell-cell interactions and cell-matrix interactions. Due to this complexity, recapitulation of lung development in vitro to promote differentiation of stem cells to lung epithelial cells has been challenging. In this protocol, decellularized lung scaffolds are used to mimic the 3-dimensional environment of the lung and generate stem cell-derived airway epithelial cells. Mouse embryonic stem cell are first differentiated to the endoderm lineage using an embryoid body (EB) culture method with activin A. Endoderm cells are then seeded onto decellularized scaffolds and cultured at air-liquid interface for up to 21 days. This technique promotes differentiation of seeded cells to functional airway epithelial cells (ciliated cells, club cells, and basal cells) without additional growth factor supplementation. This culture setup is defined, serum-free, inexpensive, and reproducible. Although there is limited contamination from non-lung endoderm lineages in culture, this protocol only generates airway epithelial populations and does not give rise to alveolar epithelial cells. Airway epithelia generated with this protocol can be used to study cell-matrix interactions during lung organogenesis and for disease modeling or drug-discovery platforms of airway-related pathologies such as cystic fibrosis. PMID:27214388

  12. P220-S Dual-Purpose Insect Cell Expression Vector for Transient Transfection and Baculovirus Generation

    OpenAIRE

    Loomis, K.; ROCKWELL, C; Sternard, H.; Novy, R.

    2007-01-01

    Baculovirus-mediated expression has proven to be a robust method of generating recombinant proteins from insect cells. However, generating baculovirus recombinants using traditional techniques is time consuming and tedious. To accelerate the process of insect cell expression, EMD developed a rapid transient transfection-based approach, the InsectDirect System. This approach is well suited for the rapid generation of small to moderate amounts of recombinant protein. For situations that demand ...

  13. Generation and multiplication of plantlets from callus derived from Haplopappus gracilus (Nutt.) Gray and their karyotype analysis

    Science.gov (United States)

    Kann, R. P.; O'Connor, S. A.; Levine, H. G.; Krikorian, A. D.

    1991-01-01

    Unopened flower heads of Haplopappus gracilis (2n = 4) provided primary explants for callus production and subsequent induction of organized growth. Callus was initiated from small (3-5 mm in length) floral buds with benzylaminopurine (BAP) (44.4 micromoles; 10 mg/l) and naphthalene acetic acid (NAA) (0.54 micromole; 0.1 mg/l). Lowering the BAP level to 4.44 micromoles (1 mg/l) but maintaining the NAA level, gave rise to organized but highly compressed shoot growing points from an otherwise undifferentiated callus mass. Shoots selected from such cultures were maintainable and could be proliferated by growing 1-1.5-cm stem tip cuttings on Murashige and Skoog basal medium (solidified with agar) containing 0.444 micromole (0.1 mg/l) BAP and 0.054 micromole (0.01 mg/l) NAA. The stem tip multiplication rates obtainable by these means permit reliable strategies for shoot multiplication or production of rooted plantlets. Prolonged subculture and maintenance of shoots on growth regulator-free medium leads to in vitro flowering and greatly reduces rooting capacity. Karyotype analysis of chromosomes from root tip cells at metaphase and chromosome measurements show that karyologically uniform plantlets (based on chromosome number and morphology) can be obtained.

  14. 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

  15. Generation of Recombinant Monoclonal Antibodies from Immunised Mice and Rabbits via Flow Cytometry and Sorting of Antigen-Specific IgG+ Memory B Cells.

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    Dale O Starkie

    Full Text Available Single B cell screening strategies, which avoid both hybridoma fusion and combinatorial display, have emerged as important technologies for efficiently sampling the natural antibody repertoire of immunized animals and humans. Having access to a range of methods to interrogate different B cell subsets provides an attractive option to ensure large and diverse panels of high quality antibody are produced. The generation of multiple antibodies and having the ability to find rare B cell clones producing IgG with unique and desirable characteristics facilitates the identification of fit-for-purpose molecules that can be developed into therapeutic agents or research reagents. Here, we describe a multi-parameter flow cytometry single-cell sorting technique for the generation of antigen-specific recombinant monoclonal antibodies from single IgG+ memory B cells. Both mouse splenocytes and rabbit PBMC from immunised animals were used as a source of B cells. Reagents staining both B cells and other unwanted cell types enabled efficient identification of class-switched IgG+ memory B cells. Concurrent staining with antigen labelled separately with two spectrally-distinct fluorophores enabled antigen-specific B cells to be identified, i.e. those which bind to both antigen conjugates (double-positive. These cells were then typically sorted at one cell per well using FACS directly into a 96-well plate containing reverse transcriptase reaction mix. Following production of cDNA, PCR was performed to amplify cognate heavy and light chain variable region genes and generate transcriptionally-active PCR (TAP fragments. These linear expression cassettes were then used directly in a mammalian cell transfection to generate recombinant antibody for further testing. We were able to successfully generate antigen-specific recombinant antibodies from both the rabbit and mouse IgG+ memory B cell subset within one week. This included the generation of an anti-TNFR2 blocking

  16. Sprouty genes prevent excessive FGF signalling in multiple cell types throughout development of the cerebellum

    Science.gov (United States)

    Yu, Tian; Yaguchi, Yuichiro; Echevarria, Diego; Martinez, Salvador; Basson, M. Albert

    2011-01-01

    Fibroblast growth factors (FGFs) and regulators of the FGF signalling pathway are expressed in several cell types within the cerebellum throughout its development. Although much is known about the function of this pathway during the establishment of the cerebellar territory during early embryogenesis, the role of this pathway during later developmental stages is still poorly understood. Here, we investigated the function of sprouty genes (Spry1, Spry2 and Spry4), which encode feedback antagonists of FGF signalling, during cerebellar development in the mouse. Simultaneous deletion of more than one of these genes resulted in a number of defects, including mediolateral expansion of the cerebellar vermis, reduced thickness of the granule cell layer and abnormal foliation. Analysis of cerebellar development revealed that the anterior cerebellar neuroepithelium in the early embryonic cerebellum was expanded and that granule cell proliferation during late embryogenesis and early postnatal development was reduced. We show that the granule cell proliferation deficit correlated with reduced sonic hedgehog (SHH) expression and signalling. A reduction in Fgfr1 dosage during development rescued these defects, confirming that the abnormalities are due to excess FGF signalling. Our data indicate that sprouty acts both cell autonomously in granule cell precursors and non-cell autonomously to regulate granule cell number. Taken together, our data demonstrate that FGF signalling levels have to be tightly controlled throughout cerebellar development in order to maintain the normal development of multiple cell types. PMID:21693512

  17. Connecting multiple spatial scales to decode the population activity of grid cells.

    Science.gov (United States)

    Stemmler, Martin; Mathis, Alexander; Herz, Andreas V M

    2015-12-01

    Mammalian grid cells fire when an animal crosses the points of an imaginary hexagonal grid tessellating the environment. We show how animals can navigate by reading out a simple population vector of grid cell activity across multiple spatial scales, even though neural activity is intrinsically stochastic. This theory of dead reckoning explains why grid cells are organized into discrete modules within which all cells have the same lattice scale and orientation. The lattice scale changes from module to module and should form a geometric progression with a scale ratio of around 3/2 to minimize the risk of making large-scale errors in spatial localization. Such errors should also occur if intermediate-scale modules are silenced, whereas knocking out the module at the smallest scale will only affect spatial precision. For goal-directed navigation, the allocentric grid cell representation can be readily transformed into the egocentric goal coordinates needed for planning movements. The goal location is set by nonlinear gain fields that act on goal vector cells. This theory predicts neural and behavioral correlates of grid cell readout that transcend the known link between grid cells of the medial entorhinal cortex and place cells of the hippocampus. PMID:26824061

  18. Isolation and Multiple Differentiation Potential Assessment of Human Gingival Mesenchymal Stem Cells

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    Yuan Gao

    2014-11-01

    Full Text Available The aim of this study was to isolate human mesenchymal stem cells (MSCs from the gingiva (GMSCs and confirm their multiple differentiation potentials, including the odontogenic lineage. GMSCs, periodontal ligament stem cells (PDLSCs and dermal stem cells (DSCs cultures were analyzed for cell shape, cell cycle, colony-forming unit-fibroblast (CFU-F and stem cell markers. Cells were then induced for osteogenic and adipogenic differentiation and analyzed for differentiation markers (alkaline phosphatase (ALP activity, mineralization nodule formation and Runx2, ALP, osteocalcin (OCN and collagen I expressions for the osteogenic differentiation, and lipid vacuole formation and PPARγ-2 expression for the adipogenic differentiation. Besides, the odontogenic differentiation potential of GMSCs induced with embryonic tooth germ cell-conditioned medium (ETGC-CM was observed. GMSCs, PDLSCs and DSCs were all stromal origin. PDLSCs showed much higher osteogenic differentiation ability but lower adipogenic differentiation potential than DSCs. GMSCs showed the medial osteogenic and adipogenic differentiation potentials between those of PDLSCs and DSCs. GMSCs were capable of expressing the odontogenic genes after ETGC-CM induction. This study provides evidence that GMSCs can be used in tissue engineering/regeneration protocols as an approachable stem cell source.

  19. Lsd1 restricts the number of germline stem cells by regulating multiple targets in escort cells.

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    Susan Eliazer

    2014-03-01

    Full Text Available Specialized microenvironments called niches regulate tissue homeostasis by controlling the balance between stem cell self-renewal and the differentiation of stem cell daughters. However the mechanisms that govern the formation, size and signaling of in vivo niches remain poorly understood. Loss of the highly conserved histone demethylase Lsd1 in Drosophila escort cells results in increased BMP signaling outside the cap cell niche and an expanded germline stem cell (GSC phenotype. Here we present evidence that loss of Lsd1 also results in gradual changes in escort cell morphology and their eventual death. To better characterize the function of Lsd1 in different cell populations within the ovary, we performed Chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq. This analysis shows that Lsd1 associates with a surprisingly limited number of sites in escort cells and fewer, and often, different sites in cap cells. These findings indicate that Lsd1 exhibits highly selective binding that depends greatly on specific cellular contexts. Lsd1 does not directly target the dpp locus in escort cells. Instead, Lsd1 regulates engrailed expression and disruption of engrailed and its putative downstream target hedgehog suppress the Lsd1 mutant phenotype. Interestingly, over-expression of engrailed, but not hedgehog, results in an expansion of GSC cells, marked by the expansion of BMP signaling. Knockdown of other potential direct Lsd1 target genes, not obviously linked to BMP signaling, also partially suppresses the Lsd1 mutant phenotype. These results suggest that Lsd1 restricts the number of GSC-like cells by regulating a diverse group of genes and provide further evidence that escort cell function must be carefully controlled during development and adulthood to ensure proper germline differentiation.

  20. TALEN-mediated genetic tailoring as a tool to analyze the function of acquired mutations in multiple myeloma cells

    International Nuclear Information System (INIS)

    Multiple myeloma (MM) is a clonal plasma cell malignancy that is initiated by a number of mutations and the process of disease progression is characterized by further acquisition of mutations. The identification and functional characterization of these myelomagenic mutations is necessary to better understand the underlying pathogenic mechanisms in this disease. Recent advancements in next-generation sequencing have made the identification of most of these mutations a reality. However, the functional characterization of these mutations has been hampered by the lack of proper and efficient tools to dissect these mutations. Here we explored the possible utility of transcription activator-like effector nuclease (TALEN) genome engineering technology to tailoring the genome of MM cells. To test this possibility, we targeted the HPRT1 gene and found that TALENs are a very robust and efficient genome-editing tool in MM cells. Using cotransfected green fluorescent protein as an enrichment marker, single-cell subclones with desirable TALEN modifications in the HPRT1 gene were obtained in as little as 3–4 weeks of time. We believe that TALENs will greatly facilitate the functional study of somatic mutations in MM as well as other cancers

  1. Gas generation mechanism due to electrolyte decomposition in commercial lithium-ion cell

    Science.gov (United States)

    Kumai, Kazuma; Miyashiro, Hajime; Kobayashi, Yo; Takei, Katsuhito; Ishikawa, Rikio

    To elucidate the gas generation mechanism due to electrolyte decomposition in commercial lithium-ion cells after long cycling, we developed a device which can accurately determine the volume of generated gas in the cell. Experiments on Li xC 6/Li 1- xCoO 2 cells using electrolytes such as 1 M LiPF 6 in propylene carbonate (PC), dimethyl carbonate (DMC), ethyl methyl carbonate (EMC), and diethyl carbonate (DEC) are presented and discussed. In the nominal voltage range (4.2-2.5 V), compositional change due mainly to ester exchange reaction occurs, and gaseous products in the cell are little. Generated gas volume and compositional change in the electrolyte are detected largely in overcharged cells, and we discussed that gas generation due to electrolyte decomposition involves different decomposition reactions in overcharged and overdischarged cells.

  2. Evaluation of multiple hydraulic models in generating design/near-real time flood inundation extents under various geophysical settings

    Science.gov (United States)

    Liu, Z.; Rajib, M. A.; Jafarzadegan, K.; Merwade, V.

    2015-12-01

    Application of land surface/hydrologic models within an operational flood forecasting system can provide probable time of occurrence and magnitude of streamflow at specific locations along a stream. Creating time-varying spatial extent of flood inundation and depth requires the use of a hydraulic or hydrodynamic model. Models differ in representing river geometry and surface roughness which can lead to different output depending on the particular model being used. The result from a single hydraulic model provides just one possible realization of the flood extent without capturing the uncertainty associated with the input or the model parameters. The objective of this study is to compare multiple hydraulic models toward generating ensemble flood inundation extents. Specifically, relative performances of four hydraulic models, including AutoRoute, HEC-RAS, HEC-RAS 2D, and LISFLOOD are evaluated under different geophysical conditions in several locations across the United States. By using streamflow output from the same hydrologic model (SWAT in this case), hydraulic simulations are conducted for three configurations: (i) hindcasting mode by using past observed weather data at daily time scale in which models are being calibrated against USGS streamflow observations, (ii) validation mode using near real-time weather data at sub-daily time scale, and (iii) design mode with extreme streamflow data having specific return periods. Model generated inundation maps for observed flood events both from hindcasting and validation modes are compared with remotely sensed images, whereas the design mode outcomes are compared with corresponding FEMA generated flood hazard maps. The comparisons presented here will give insights on probable model-specific nature of biases and their relative advantages/disadvantages as components of an operational flood forecasting system.

  3. NF-kappa B modulation is involved in celastrol induced human multiple myeloma cell apoptosis.

    Directory of Open Access Journals (Sweden)

    Haiwen Ni

    Full Text Available Celastrol is an active compound extracted from the root bark of the traditional Chinese medicine Tripterygium wilfordii Hook F. To investigate the effect of celastrol on human multiple myeloma cell cycle arrest and apoptosis and explore its molecular mechanism of action. The activity of celastrol on LP-1 cell proliferation was detected by WST-8 assay. The celastrol-induced cell cycle arrest was analyzed by flow cytometry after propidium iodide staining. Nuclear translocation of the nuclear factor kappa B (NF-κB was observed by fluorescence microscope. Celastrol inhibited cell proliferation of LP-1 myeloma cell in a dose-dependent manner with IC50 values of 0.8817 µM, which was mediated through G1 cell cycle arrest and p27 induction. Celastrol induced apoptosis in LP-1 and RPMI 8226 myeloma cells in a time and dose dependent manner, and it involved Caspase-3 activation and NF-κB pathway. Celastrol down-modulated antiapoptotic proteins including Bcl-2 and survivin expression. The expression of NF-κB and IKKa were decreased after celastrol treatment. Celastrol effectively blocked the nuclear translocation of the p65 subunit and induced human multiple myeloma cell cycle arrest and apoptosis by p27 upregulation and NF-kB modulation. It has been demonstrated that the effect of celastrol on NF-kB was HO-1-independent by using zinc protoporphyrin-9 (ZnPPIX, a selective heme oxygenase inhibitor. From the results, it could be inferred that celastrol may be used as a NF-kB inhibitor to inhibit myeloma cell proliferation.

  4. Cyclic AMP induces apoptosis in multiple myeloma cells and inhibits tumor development in a mouse myeloma model

    International Nuclear Information System (INIS)

    Multiple myeloma is an incurable disease requiring the development of effective therapies which can be used clinically. We have elucidated the potential for manipulating the cAMP signaling pathway as a target for inhibiting the growth of multiple myeloma cells. As a model system, we primarily used the murine multiple myeloma cell line MOPC315 which can be grown both in vivo and in vitro. Human multiple myeloma cell lines U266, INA-6 and the B-cell precursor acute lymphoblastic leukemia cell line Reh were used only for in vitro studies. Cell death was assessed by flow cytometry and western blot analysis after treatment with cAMP elevating agents (forskolin, prostaglandin E2 and rolipram) and cAMP analogs. We followed tumor growth in vivo after forskolin treatment by imaging DsRed-labelled MOPC315 cells transplanted subcutaneously in BALB/c nude mice. In contrast to the effect on Reh cells, 50 μM forskolin more than tripled the death of MOPC315 cells after 24 h in vitro. Forskolin induced cell death to a similar extent in the human myeloma cell lines U266 and INA-6. cAMP-mediated cell death had all the typical hallmarks of apoptosis, including changes in the mitochondrial membrane potential and cleavage of caspase 3, caspase 9 and PARP. Forskolin also inhibited the growth of multiple myeloma cells in a mouse model in vivo. Elevation of intracellular levels of cAMP kills multiple myeloma cells in vitro and inhibits development of multiple myeloma in vivo. This strongly suggests that compounds activating the cAMP signaling pathway may be useful in the field of multiple myeloma

  5. B cells are multifunctional players in multiple sclerosis pathogenesis: insights from therapeutic interventions

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    Nele eClaes

    2015-12-01

    Full Text Available Multiple sclerosis (MS is a severe disease of the central nervous system (CNS characterized by autoimmune inflammation and neurodegeneration. Historically, damage to the CNS was thought to be mediated predominantly by activated pro-inflammatory T cells. B cell involvement in the pathogenesis of MS was solely attributed to autoantibody production. The first clues for the involvement of antibody-independent B cell functions in MS pathology came from positive results in clinical trials of the B cell depleting treatment rituximab in patients with relapsing-remitting (RR MS. The survival of antibody-secreting plasma cells and decrease in T cell numbers indicated the importance of other B cell functions in MS such as antigen presentation, costimulation and cytokine production. Rituximab provided us with an example of how clinical trials can lead to new research opportunities concerning B cell biology. Moreover, analysis of the antibody-independent B cell functions in MS has gained interest since these trials. Limited information is present on the effects of current immunomodulatory therapies on B cell functions, although effects of both first-line (interferon, glatiramer acetate, dimethyl fumarate and teriflunomide, second-line (fingolimod, natalizumab and even third-line (monoclonal antibody therapies treatments on B cell subtype distribution, expression of functional surface markers and secretion of different cytokines by B cells have been studied to some extent. In this review, we summarize the effects of different MS related treatments on B cell functions that have been described up to now in order to find new research opportunities and contribute to the understanding of the pathogenesis of MS.

  6. Characterization of baculovirus Autographa californica multiple nuclear polyhedrosis virus infection in mammalian cells

    International Nuclear Information System (INIS)

    The baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) is used as a vector in many gene therapy studies. Wild-type AcMNPV infects many mammalian cell types in vitro, but does not replicate. We investigated the dynamics of AcMNPV genomic DNA in infected mammalian cells and used flow cytometric analysis to demonstrate that recombinant baculovirus containing a cytomegalovirus immediate early promoter/enhancer with green fluorescent protein (GFP) expressed high levels of GFP in Huh-7 cells, but not B16, Raw264.7, or YAC-1 cells. The addition of butyrate, a deacetylase inhibitor, markedly enhanced the percentage of GFP-expressing Huh-7 and B16 cells, but not Raw264.7 and YAC-1 cells. The addition of 5-aza-2'-deoxycytidine, a DNA methylation inhibitor, had no enhancing effect. Polymerase chain reaction analysis using AcMNPV-gp64-specific primers indicated that AcMNPV infected not only Huh-7 and B16 cells, but also Raw264.7 and YAC-1 cells in vitro. The genomic DNA was detected in Huh-7 and B16 cells 96 h after infection. Genomic AcMNPV DNA in YAC-1 cells was not transported to the nucleus. Luciferase assay indicated that AcMNPV p35 gene mRNA and p35 promoter activity were clearly expressed only in Huh-7 and B16 cells. These results suggest that viral genomic DNA expression is restricted by different host cell factors, such as degradation, deacetylation, and inhibition of nuclear transport, depending on the mammalian cell type

  7. The New Generation of Beta-Cells: Replication, Stem Cell Differentiation, and the Role of Small Molecules

    OpenAIRE

    Borowiak, Malgorzata

    2010-01-01

    Diabetic patients suffer from the loss of insulin-secreting β-cells, or from an improper working β-cell mass. Due to the increasing prevalence of diabetes across the world, there is a compelling need for a renewable source of cells that could replace pancreatic β-cells. In recent years, several promising approaches to the generation of new β-cells have been developed. These include directed differentiation of pluripotent cells such as embryonic stem (ES) cells or induced pluripotent stem (iPS...

  8. Epigenetic Reprogramming of Human Embryonic Stem Cells into Skeletal Muscle Cells and Generation of Contractile Myospheres

    Directory of Open Access Journals (Sweden)

    Sonia Albini

    2013-03-01

    Full Text Available Direct generation of a homogeneous population of skeletal myoblasts from human embryonic stem cells (hESCs and formation of three-dimensional contractile structures for disease modeling in vitro are current challenges in regenerative medicine. Previous studies reported on the generation of myoblasts from ESC-derived embryoid bodies (EB, but not from undifferentiated ESCs, indicating the requirement for mesodermal transition to promote skeletal myogenesis. Here, we show that selective absence of the SWI/SNF component BAF60C (encoded by SMARCD3 confers on hESCs resistance to MyoD-mediated activation of skeletal myogenesis. Forced expression of BAF60C enables MyoD to directly activate skeletal myogenesis in hESCs by instructing MyoD positioning and allowing chromatin remodeling at target genes. BAF60C/MyoD-expressing hESCs are epigenetically committed myogenic progenitors, which bypass the mesodermal requirement and, when cultured as floating clusters, give rise to contractile three-dimensional myospheres composed of skeletal myotubes. These results identify BAF60C as a key epigenetic determinant of hESC commitment to the myogenic lineage and establish the molecular basis for the generation of hESC-derived myospheres exploitable for “disease in a dish” models of muscular physiology and dysfunction.

  9. Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres.

    Science.gov (United States)

    Albini, Sonia; Coutinho, Paula; Malecova, Barbora; Giordani, Lorenzo; Savchenko, Alex; Forcales, Sonia Vanina; Puri, Pier Lorenzo

    2013-03-28

    Direct generation of a homogeneous population of skeletal myoblasts from human embryonic stem cells (hESCs) and formation of three-dimensional contractile structures for disease modeling in vitro are current challenges in regenerative medicine. Previous studies reported on the generation of myoblasts from ESC-derived embryoid bodies (EB), but not from undifferentiated ESCs, indicating the requirement for mesodermal transition to promote skeletal myogenesis. Here, we show that selective absence of the SWI/SNF component BAF60C (encoded by SMARCD3) confers on hESCs resistance to MyoD-mediated activation of skeletal myogenesis. Forced expression of BAF60C enables MyoD to directly activate skeletal myogenesis in hESCs by instructing MyoD positioning and allowing chromatin remodeling at target genes. BAF60C/MyoD-expressing hESCs are epigenetically committed myogenic progenitors, which bypass the mesodermal requirement and, when cultured as floating clusters, give rise to contractile three-dimensional myospheres composed of skeletal myotubes. These results identify BAF60C as a key epigenetic determinant of hESC commitment to the myogenic lineage and establish the molecular basis for the generation of hESC-derived myospheres exploitable for "disease in a dish" models of muscular physiology and dysfunction.

  10. Utility of Lymphoblastoid Cell Lines for Induced Pluripotent Stem Cell Generation

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    Satish Kumar

    2016-01-01

    Full Text Available A large number of EBV immortalized LCLs have been generated and maintained in genetic/epidemiological studies as a perpetual source of DNA and as a surrogate in vitro cell model. Recent successes in reprograming LCLs into iPSCs have paved the way for generating more relevant in vitro disease models using this existing bioresource. However, the overall reprogramming efficiency and success rate remain poor and very little is known about the mechanistic changes that take place at the transcriptome and cellular functional level during LCL-to-iPSC reprogramming. Here, we report a new optimized LCL-to-iPSC reprogramming protocol using episomal plasmids encoding pluripotency transcription factors and mouse p53DD (p53 carboxy-terminal dominant-negative fragment and commercially available reprogramming media. We achieved a consistently high reprogramming efficiency and 100% success rate using this optimized protocol. Further, we investigated the transcriptional changes in mRNA and miRNA levels, using FC-abs ≥ 2.0 and FDR ≤ 0.05 cutoffs; 5,228 mRNAs and 77 miRNAs were differentially expressed during LCL-to-iPSC reprogramming. The functional enrichment analysis of the upregulated genes and activation of human pluripotency pathways in the reprogrammed iPSCs showed that the generated iPSCs possess transcriptional and functional profiles very similar to those of human ESCs.

  11. Instrumentation for simultaneous kinetic imaging of multiple fluorophores in single living cells

    Science.gov (United States)

    Morris, Stephen J.; Beatty, Diane M.; Welling, Larry W.; Wiegmann, Thomas B.

    1991-05-01

    Low-light fluorescence video microscopy has established itself as an excellent method for investigations of cell dynamics. There is a growing interest in resolving multiple images of 'ratio' fluorophores like indo or BCECF or the emission from multiple dyes placed in the same cell system. For rapid kinetic studies, the problems of photodynamic damage and photobleaching on one hand and the need for good spatial and temporal resolution on the other, press the resolution of the instrumentation. Rapid resolution of multiple probes at multiple wavelengths presents a third set of problems of exciting the probes and appropriately imaging the emitted light. The authors have designed a new real-time low-light fluorescence video microscope for capturing intensified images of up to four dyes contained in the same cell system. These can be two dual-emission wavelength 'ratio' dyes or multiple dyes. The optics allow simultaneous excitation of up to four fluorophores and the real-time (30 frames/second) capture of four separate fluorescence emission images. Each emission wavelength is imaged simultaneously by one of four cameras, then digitized and appropriately combined at standard video frame rates to be stored at high resolution on tape or video disk for further off-line correction and analysis. The design has no moving parts in its optical train, which overcomes a number of technical difficulties encountered in filter wheel or mechanical shutter designs for multiple imaging. The instrument can be assembled form off-the-shelf components. Coupled to compatible image processing software utilizing PC-AT computers, it can be realized for relatively low cost. Two examples of simultaneous multi-parameter imaging are presented. Synchronous observations of calcium and pH distribution in kidney epithelial cells, loaded with both indo-1 and SNARF-1TM, show that both are altered in response to ionomycin treatment; however, the kinetics for the two changes are quite different

  12. Generation and characterization of induced pluripotent stem cells from Aid-deficient mice.

    Directory of Open Access Journals (Sweden)

    Ren Shimamoto

    Full Text Available It has been shown that DNA demethylation plays a pivotal role in the generation of induced pluripotent stem (iPS cells. However, the underlying mechanism of this action is still unclear. Previous reports indicated that activation-induced cytidine deaminase (Aid, also known as Aicda is involved in DNA demethylation in several developmental processes, as well as cell fusion-mediated reprogramming. Based on these reports, we hypothesized that Aid may be involved in the DNA demethylation that occurs during the generation of iPS cells. In this study, we examined the function of Aid in iPS cell generation using Aid knockout (Aid⁻/⁻ mice expressing a GFP reporter under the control of a pluripotent stem cell marker, Nanog. By introducing Oct3/4, Sox2, Klf4 and c-Myc, Nanog-GFP-positive iPS cells could be generated from the fibroblasts and primary B cells of Aid⁻/⁻ mice. Their induction efficiency was similar to that of wild-type (Aid⁺/⁺ iPS cells. The Aid⁻/⁻ iPS cells showed normal proliferation and gave rise to chimeras, indicating their capacity for self-renewal and pluripotency. A comprehensive DNA methylation analysis showed only a few differences between Aid⁺/⁺ and Aid⁻/⁻ iPS cells. These data suggest that Aid does not have crucial functions in DNA demethylation during iPS cell generation.

  13. Cerebral blood flow and red cell delivery in normal subjects and in multiple sclerosis

    International Nuclear Information System (INIS)

    Regional cerebral blood flow (rCBF) was determined in 77 normal females and 53 normal males of different ages and in 26 men and 45 women with multiple sclerosis by the inhalation of radioactive Xe133 method. In the normal subjects the CBF was relatively high in the teens and fell, at first rapidly and then slowly in both sexes with age. During adult life the flow in females was significantly higher than in males. The delivery of packed red cells (RCD) was determined by multiplying the CBF by the percentage concentration of red cells (HCT). The RCD for both sexes was nearly the same. In the patients with multiple sclerosis there occurred a progressive generalized decrease in CBF and in RCD with age which was significantly greater than observed in normal subjects. The rate of decrease in CBF and RCD correlated directly with the rate of progress of the disease

  14. CRISPR/Cas9-Mediated Rapid Generation of Multiple Mouse Lines Identified Ccdc63 as Essential for Spermiogenesis

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    Samantha A. M. Young

    2015-10-01

    Full Text Available Spermatozoa are flagellated cells whose role in fertilization is dependent on their ability to move towards an oocyte. The structure of the sperm flagella is highly conserved across species, and much of what is known about this structure is derived from studies utilizing animal models. One group of proteins essential for the movement of the flagella are the dyneins. Using the advanced technology of CRISPR/Cas9 we have targeted three dynein group members; Dnaic1, Wdr63 and Ccdc63 in mice. All three of these genes are expressed strongly in the testis. We generated mice with amino acid substitutions in Dnaic1 to analyze two specific phosphorylation events at S124 and S127, and generated simple knockouts of Wdr63 and Ccdc63. We found that the targeted phosphorylation sites in Dnaic1 were not essential for male fertility. Similarly, Wdr63 was not essential for male fertility; however, Ccdc63 removal resulted in sterile male mice due to shortened flagella. This study demonstrates the versatility of the CRISPR/Cas9 system to generate animal models of a highly complex system by introducing point mutations and simple knockouts in a fast and efficient manner.

  15. Models of charge pair generation in organic solar cells.

    Science.gov (United States)

    Few, Sheridan; Frost, Jarvist M; Nelson, Jenny

    2015-01-28

    Efficient charge pair generation is observed in many organic photovoltaic (OPV) heterojunctions, despite nominal electron-hole binding energies which greatly exceed the average thermal energy. Empirically, the efficiency of this process appears to be related to the choice of donor and acceptor materials, the resulting sequence of excited state energy levels and the structure of the interface. In order to establish a suitable physical model for the process, a range of different theoretical studies have addressed the nature and energies of the interfacial states, the energetic profile close to the heterojunction and the dynamics of excited state transitions. In this paper, we review recent developments underpinning the theory of charge pair generation and phenomena, focussing on electronic structure calculations, electrostatic models and approaches to excited state dynamics. We discuss the remaining challenges in achieving a predictive approach to charge generation efficiency. PMID:25462189

  16. ATP release, generation and hydrolysis in exocrine pancreatic duct cells

    DEFF Research Database (Denmark)

    Kowal, Justyna Magdalena; Yegutkin, G.G.; Novak, Ivana

    2015-01-01

    purine homeostasis in a pancreatic duct cell model involving: ATP release by several mechanisms and subsequent nucleotide breakdown and ATP regeneration via counteracting nucleotide-inactivating and nucleotide-phosphorylating ecto-enzymes. We suggest that extracellular ATP homeostasis in pancreatic ducts......Extracellular adenosine triphosphate (ATP) regulates pancreatic duct function via P2Y and P2X receptors. It is well known that ATP is released from upstream pancreatic acinar cells. The ATP homeostasis in pancreatic ducts, which secrete bicarbonate-rich fluid, has not yet been examined. First, our...... aim was to reveal whether pancreatic duct cells release ATP locally and whether they enzymatically modify extracellular nucleotides/sides. Second, we wished to explore which physiological and pathophysiological factors may be important in these processes. Using a human pancreatic duct cell line, Capan...

  17. Design and screening of a glial cell-specific, cell penetrating peptide for therapeutic applications in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Corey Heffernan

    Full Text Available Multiple Sclerosis (MS is an autoimmune, neurodegenerative disease of the central nervous system (CNS characterized by demyelination through glial cell loss. Current and proposed therapeutic strategies to arrest demyelination and/or promote further remyelination include: (i modulation of the host immune system; and/or (ii transplantation of myelinating/stem or progenitor cells to the circulation or sites of injury. However, significant drawbacks are inherent with both approaches. Cell penetrating peptides (CPP are short amino acid sequences with an intrinsic ability to translocate across plasma membranes, and theoretically represent an attractive vector for delivery of therapeutic peptides or nanoparticles to glia to promote cell survival or remyelination. The CPPs described to date are commonly non-selective in the cell types they transduce, limiting their therapeutic application in vivo. Here, we describe a theoretical framework for design of a novel CPP sequence that selectively transduces human glial cells (excluding non-glial cell types, and conduct preliminary screens of purified, recombinant CPPs with immature and matured human oligodendrocytes and astrocytes, and two non-glial cell types. A candidate peptide, termed TD2.2, consistently transduced glial cells, was significantly more effective at transducing immature oligodendrocytes than matured progeny, and was virtually incapable of transducing two non-glial cell types: (i human neural cells and (ii human dermal fibroblasts. Time-lapse confocal microscopy confirms trafficking of TD2.2 (fused to EGFP to mature oligodendrocytes 3-6 hours after protein application in vitro. We propose selectivity of TD2.2 for glial cells represents a new therapeutic strategy for the treatment of glial-related disease, such as MS.

  18. High Temperature Solid Oxide Fuel Cell Generator Development

    Energy Technology Data Exchange (ETDEWEB)

    Joseph Pierre

    2007-09-30

    This report describes the results of the tubular SOFC development program from August 22, 1997 to September 30, 2007 under the Siemens/U.S. Department of Energy Cooperative Agreement. The technical areas discussed include cell manufacturing development, cell power enhancement, SOFC module and system cost reduction and technology advancement, and our field unit test program. Whereas significant progress has been made toward commercialization, significant effort remains to achieve our cost, performance and reliability targets for successful commercialization.

  19. Multiparametric flow cytometry profiling of neoplastic plasma cells in multiple myeloma

    DEFF Research Database (Denmark)

    Johnsen, Hans E; Bøgsted, Martin; Klausen, Tobias W;

    2010-01-01

    The clinical impact of multiparametric flow cytometry (MFC) in multiple myeloma (MM) is still unclear and under evaluation. Further progress relies on multiparametric profiling of the neoplastic plasma cell (PC) compartment to provide an accurate image of the stage of differentiation. The primary......, and predictive information useful in clinical practice, which will be prospectively validated within the European Myeloma Network (EMN). © 2010 International Clinical Cytometry Society....

  20. Mast Cells in the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

    OpenAIRE

    Rosetta Pedotti; Massimo Costanza; Colombo, Mario P.

    2012-01-01

    Mast cells (MCs) are best known as key immune players in immunoglobulin E (IgE)-dependent allergic reactions. In recent years, several lines of evidence have suggested that MCs might play an important role in several pathological conditions, including autoimmune disorders such as multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Since their first description in MS plaques in the late 1800s, much effort has been put into elucidating the contri...