WorldWideScience

Sample records for efficient terminal differentiation

  1. Efficiency analysis of container ports and terminals

    OpenAIRE

    Liu, Q.

    2010-01-01

    In the past two decades the steady growth of seaborne trade has resulted in the increase of container ships, container ports and their terminals. The structure of the shipping market is, moreover, continuously evolving. On the carrier side, shipping companies form consortia and alliances; on the port side, global terminal operators and dedicated container terminals are emerging. The aim of this research is to evaluate the efficiency of container ports and terminals and to study...

  2. Efficient, Differentially Private Point Estimators

    OpenAIRE

    Smith, Adam

    2008-01-01

    Differential privacy is a recent notion of privacy for statistical databases that provides rigorous, meaningful confidentiality guarantees, even in the presence of an attacker with access to arbitrary side information. We show that for a large class of parametric probability models, one can construct a differentially private estimator whose distribution converges to that of the maximum likelihood estimator. In particular, it is efficient and asymptotically unbiased. This result provides (furt...

  3. Mechanisms of dealing with DNA damage in terminally differentiated cells

    Energy Technology Data Exchange (ETDEWEB)

    Fortini, P. [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Dogliotti, E., E-mail: eugenia.dogliotti@iss.it [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome (Italy)

    2010-03-01

    To protect genomic integrity living cells that are continuously exposed to DNA-damaging insults are equipped with an efficient defence mechanism termed the DNA damage response. Its function is to eliminate DNA damage through DNA repair and to remove damaged cells by apoptosis. The DNA damage response has been investigated mainly in proliferating cells, in which the cell cycle machinery is integrated with the DNA damage signalling. The current knowledge of the mechanisms of DNA repair, DNA damage signalling and cell death of post-mitotic cells that have undergone irreversible cell cycle withdrawal will be reviewed. Evidence will be provided that the protection of the genome integrity in terminally differentiated cells is achieved by different strategies than in proliferating cells.

  4. Mechanisms of dealing with DNA damage in terminally differentiated cells

    International Nuclear Information System (INIS)

    Fortini, P.; Dogliotti, E.

    2010-01-01

    To protect genomic integrity living cells that are continuously exposed to DNA-damaging insults are equipped with an efficient defence mechanism termed the DNA damage response. Its function is to eliminate DNA damage through DNA repair and to remove damaged cells by apoptosis. The DNA damage response has been investigated mainly in proliferating cells, in which the cell cycle machinery is integrated with the DNA damage signalling. The current knowledge of the mechanisms of DNA repair, DNA damage signalling and cell death of post-mitotic cells that have undergone irreversible cell cycle withdrawal will be reviewed. Evidence will be provided that the protection of the genome integrity in terminally differentiated cells is achieved by different strategies than in proliferating cells.

  5. Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation.

    Directory of Open Access Journals (Sweden)

    Lianghua Bin

    Full Text Available The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq profiling approach, we found that forkhead box c 1 (FOXC1 was significantly up-regulated in human normal primary KC during the course of differentiation. This observation was validated in human normal primary KC from several different donors and human skin biopsies. Silencing FOXC1 in human normal primary KC undergoing differentiation led to significant down-regulation of late terminal differentiation genes markers including epidermal differentiation complex genes, keratinization genes, sphingolipid/ceramide metabolic process genes and epidermal specific cell-cell adhesion genes. We further demonstrated that FOXC1 works down-stream of ZNF750 and KLF4, and upstream of GRHL3. Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network.

  6. A hanging drop culture method to study terminal erythroid differentiation.

    Science.gov (United States)

    Gutiérrez, Laura; Lindeboom, Fokke; Ferreira, Rita; Drissen, Roy; Grosveld, Frank; Whyatt, David; Philipsen, Sjaak

    2005-10-01

    To design a culture method allowing the quantitative and qualitative analysis of terminal erythroid differentiation. Primary erythroid progenitors derived either from mouse tissues or from human umbilical cord blood were differentiated using hanging drop cultures and compared to methylcellulose cultures. Cultured cells were analyzed by FACS to assess differentiation. We describe a practical culture method by adapting the previously described hanging drop culture system to conditions allowing terminal differentiation of primary erythroid progenitors. Using minimal volumes of media and small numbers of cells, we obtained quantitative terminal erythroid differentiation within two days of culture in the case of murine cells and 4 days in the case of human cells. The established methods for ex vivo culture of primary erythroid progenitors, such as methylcellulose-based burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) assays, allow the detection of committed erythroid progenitors but are of limited value to study terminal erythroid differentiation. We show that the application of hanging drop cultures is a practical alternative that, in combination with clonogenic assays, enables a comprehensive assessment of the behavior of primary erythroid cells ex vivo in the context of genetic and drug-induced perturbations.

  7. Osteogenic cell differentiation on H-terminated and O-terminated nanocrystalline diamond films

    Directory of Open Access Journals (Sweden)

    Liskova J

    2015-01-01

    Full Text Available Jana Liskova,1 Oleg Babchenko,2 Marian Varga,2 Alexander Kromka,2 Daniel Hadraba,1 Zdenek Svindrych,1 Zuzana Burdikova,1 Lucie Bacakova1 1Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic; 2Institute of Physics, Academy of Sciences of the Czech Republic, Prague, Czech Republic Abstract: Nanocrystalline diamond (NCD films are promising materials for bone implant coatings because of their biocompatibility, chemical resistance, and mechanical hardness. Moreover, NCD wettability can be tailored by grafting specific atoms. The NCD films used in this study were grown on silicon substrates by microwave plasma-enhanced chemical vapor deposition and grafted by hydrogen atoms (H-termination or oxygen atoms (O-termination. Human osteoblast-like Saos-2 cells were used for biological studies on H-terminated and O-terminated NCD films. The adhesion, growth, and subsequent differentiation of the osteoblasts on NCD films were examined, and the extracellular matrix production and composition were quantified. The osteoblasts that had been cultivated on the O-terminated NCD films exhibited a higher growth rate than those grown on the H-terminated NCD films. The mature collagen fibers were detected in Saos-2 cells on both the H-terminated and O-terminated NCD films; however, the quantity of total collagen in the extracellular matrix was higher on the O-terminated NCD films, as were the amounts of calcium deposition and alkaline phosphatase activity. Nevertheless, the expression of genes for osteogenic markers – type I collagen, alkaline phosphatase, and osteocalcin – was either comparable on the H-terminated and O-terminated films or even lower on the O-terminated films. In conclusion, the higher wettability of the O-terminated NCD films is promising for adhesion and growth of osteoblasts. In addition, the O-terminated surface also seems to support the deposition of extracellular matrix proteins and extracellular matrix

  8. The death effector domains of caspase-8 induce terminal differentiation.

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    Ainhoa Mielgo

    2009-11-01

    Full Text Available The differentiation and senescence programs of metazoans play key roles in regulating normal development and preventing aberrant cell proliferation, such as cancer. These programs are intimately associated with both the mitotic and apoptotic pathways. Caspase-8 is an apical apoptotic initiator that has recently been appreciated to coordinate non-apoptotic roles in the cell. Most of these functions are attributed to the catalytic domain, however, the amino-terminal death effector domains (DEDs, which belong to the death domain superfamily of proteins, can also play key roles during development. Here we describe a novel role for caspase-8 DEDs in regulating cell differentiation and senescence. Caspase-8 DEDs accumulate during terminal differentiation and senescence of epithelial, endothelial and myeloid cells; genetic deletion or shRNA suppression of caspase-8 disrupts cell differentiation, while re-expression of DEDs rescues this phenotype. Among caspase-8 deficient neuroblastoma cells, DED expression attenuated tumor growth in vivo and proliferation in vitro via disruption of mitosis and cytokinesis, resulting in upregulation of p53 and induction of differentiation markers. These events occur independent of caspase-8 catalytic activity, but require a critical lysine (K156 in a microtubule-binding motif in the second DED domain. The results demonstrate a new function for the DEDs of caspase-8, and describe an unexpected mechanism that contributes to cell differentiation and senescence.

  9. Determinants of Operational Efficiency at Chemical Cargo Terminals

    Directory of Open Access Journals (Sweden)

    T.A. Gúlcan

    2014-06-01

    Full Text Available In today’s globalized world, one of the requirements of global supply chains is efficient transportation systems. Approximately 80 per cent of world merchandise trade carried by sea and handled by ports worldwide. For this reason, maritime transport has the strategic economic importance. Loading of oil and gas has the biggest share (%30 in commodities carried by sea and 2.9 billion tons oil and gas loaded to ship in 2013. This study is focus on chemical cargo terminals which is a special terminal form where high and international levels of safety and quality elements applied. Unlike conventional bulk cargo and container cargo operations, chemical cargo operations include own priorities, applications, and the evaluation criteria. The aim of this study is to perform a qualitative research to determine the factors affecting the operational efficiency of ship, berth and warehousing operations in chemical cargo terminals.

  10. Agent-based Security and Efficiency Estimation in Airport Terminals

    NARCIS (Netherlands)

    Janssen, S.A.M.

    We investigate the use of an Agent-based framework to identify and quantify the relationship between security and efficiency within airport terminals. In this framework, we define a novel Security Risk Assessment methodology that explicitly models attacker and defender behavior in a security

  11. Capacity Issues and Efficiency Drivers in Brazilian Bulk Terminals

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    Peter Fernandes Wanke

    2014-01-01

    Full Text Available This paper presents an efficiency analysis of Brazilian bulk terminals built upon the conjoint use of Data Envelopment Analysis and the bootstrapping technique. Confidence intervals and bias corrected central estimates were used as cornerstone tools, not only to test for significant differences on efficiency scores and their reciprocals, but also on returns to scale indicators provided by different DEA models. The results of the study suggest that most Brazilian bulk terminals present increasing returns-to-scale, that is, they are too small in size comparatively to the tasks performed, indicating a capacity shortfall. Results also suggest paths for improving efficiency levels in a scenario of low investments and capacity constraints: privatization and cargo specialization. A final contribution to the literature lays on the development a simple methodology to assess returns-to-scale based on bootstrap results.

  12. Epigenetic heterochromatin markers distinguish terminally differentiated leukocytes from incompletely differentiated leukemia cells in human blood

    Czech Academy of Sciences Publication Activity Database

    Popova, Evgenya Y.; Claxton, David F.; Lukášová, Emilie; Bird, Philip I.; Grigoryev, Sergei A.

    2006-01-01

    Roč. 34, č. 4 (2006), s. 453-462 ISSN 0301-472X R&D Projects: GA AV ČR(CZ) 1QS500040508 Institutional research plan: CEZ:AV0Z50040507 Keywords : terminal cell differentiation * chromatin structure * chronic myeloid leukemia Subject RIV: BO - Biophysics Impact factor: 3.408, year: 2006

  13. PU.1 silencing leads to terminal differentiation of erythroleukemia cells

    International Nuclear Information System (INIS)

    Atar, Orna; Levi, Ben-Zion

    2005-01-01

    The transcription factor PU.1 plays a central role in development and differentiation of hematopoietic cells. Evidence from PU.1 knockout mice indicates a pivotal role for PU.1 in myeloid lineage and B-lymphocyte development. In addition, PU.1 is a key player in the development of Friend erythroleukemia disease, which is characterized by proliferation and differentiation arrest of proerythrocytes. To study the role of PU.1 in erythroleukemia, we have used murine erythroleukemia cells, isolated from Friend virus-infected mice. Expression of PU.1 small interfering RNA in these cells led to significant inhibition of PU.1 levels. This was accompanied by inhibition of proliferation and restoration in the ability of the proerythroblastic cells to produce hemoglobin, i.e., reversion of the leukemic phenotype. The data suggest that overexpression of PU.1 gene is the immediate cause for maintaining the leukemic phenotype of the disease by retaining the self-renewal capacity of transformed erythroblastic cells and by blocking the terminal differentiation program towards erythrocytes

  14. Determinants of Operational Efficiency at Chemical Cargo Terminals

    OpenAIRE

    T.A. Gúlcan; S. Esmer; Y. Zorba; G. Şengónúl

    2014-01-01

    In today’s globalized world, one of the requirements of global supply chains is efficient transportation systems. Approximately 80 per cent of world merchandise trade carried by sea and handled by ports worldwide. For this reason, maritime transport has the strategic economic importance. Loading of oil and gas has the biggest share (%30) in commodities carried by sea and 2.9 billion tons oil and gas loaded to ship in 2013. This study is focus on chemical cargo terminals which is a special ter...

  15. Minimum Efficient Scale (MES) and preferred scale of container terminals

    OpenAIRE

    Kaselimi, Evangelia N.; Notteboom, Theo E.; Pallis, Athanasios A.; Farrell, Sheila

    2011-01-01

    Abstract: The decision on the scale of a port terminal affects the terminals managerial, operational and competitive position in all the phases of its life. It also affects competition structures in the port in which the terminal is operating, and has a potential impact on other terminals. Port authorities and terminal operators need to know the scale of the terminal when engaging in concession agreements. In economic theory the scale of a plant/firm is typically defined in relation to the Mi...

  16. The effect of dexamethasone and triiodothyronine on terminal differentiation of primary bovine chondrocytes and chondrogenically differentiated mesenchymal stem cells.

    Science.gov (United States)

    Randau, Thomas M; Schildberg, Frank A; Alini, Mauro; Wimmer, Matthias D; Haddouti, El-Mustapha; Gravius, Sascha; Ito, Keita; Stoddart, Martin J

    2013-01-01

    The newly evolved field of regenerative medicine is offering solutions in the treatment of bone or cartilage loss and deficiency. Mesenchymal stem cells, as well as articular chondrocytes, are potential cells for the generation of bone or cartilage. The natural mechanism of bone formation is that of endochondral ossification, regulated, among other factors, through the hormones dexamethasone and triiodothyronine. We investigated the effects of these hormones on articular chondrocytes and chondrogenically differentiated mesenchymal stem cells, hypothesizing that these hormones would induce terminal differentiation, with chondrocytes and differentiated stem cells being similar in their response. Using a 3D-alginate cell culture model, bovine chondrocytes and chondrogenically differentiated stem cells were cultured in presence of triiodothyronine or dexamethasone, and cell proliferation and extracellular matrix production were investigated. Collagen mRNA expression was measured by real-time PCR. Col X mRNA and alkaline phosphatase were monitored as markers of terminal differentiation, a prerequisite of endochondral ossification. The alginate culture system worked well, both for the culture of chondrocytes and for the chondrogenic differentiation of mesenchymal stem cells. Dexamethasone led to an increase in glycosaminoglycan production. Triiodothyronine increased the total collagen production only in chondrocytes, where it also induced signs of terminal differentiation, increasing both collagen X mRNA and alkaline phosphatase activity. Dexamethasone induced terminal differentiation in the differentiated stem cells. The immature articular chondrocytes used in this study seem to be able to undergo terminal differentiation, pointing to their possible role in the onset of degenerative osteoarthritis, as well as their potential for a cell source in bone tissue engineering. When chondrocyte-like cells, after their differentiation, can indeed be moved on towards terminal

  17. Technical Efficiency Analysis of Container Terminals in the Middle Eastern Region

    Directory of Open Access Journals (Sweden)

    Ebrahim Sharaf Almawsheki

    2015-12-01

    Full Text Available Despite an increasing number of studies on the efficiency of container terminals, their focus has mostly been on advanced and emerging markets. There are limited studies on container terminals in developing countries such as those of the Middle Eastern region, which are located in a critical geographic position in the international maritime route between the East and the West. Information on their potential for development relative to other terminals worldwide is thus not readily available. This study aims to evaluate the technical efficiency of 19 container terminals in the Middle Eastern region. The DEA approach is used to measure technical efficiency, and slack variable analysis identifies potential areas of improvement for inefficient terminals. The results show that the Jebel Ali, Salalah and Beirut container terminals are the most efficient terminals in the region, and that the least efficient is the terminal in Aden. The results provide valuable information for terminal managers, helping to develop resource utilisation for steady development in operational efficiency.

  18. Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer.

    Science.gov (United States)

    Sung, Li-Ying; Gao, Shaorong; Shen, Hongmei; Yu, Hui; Song, Yifang; Smith, Sadie L; Chang, Ching-Chien; Inoue, Kimiko; Kuo, Lynn; Lian, Jin; Li, Ao; Tian, X Cindy; Tuck, David P; Weissman, Sherman M; Yang, Xiangzhong; Cheng, Tao

    2006-11-01

    Since the creation of Dolly via somatic cell nuclear transfer (SCNT), more than a dozen species of mammals have been cloned using this technology. One hypothesis for the limited success of cloning via SCNT (1%-5%) is that the clones are likely to be derived from adult stem cells. Support for this hypothesis comes from the findings that the reproductive cloning efficiency for embryonic stem cells is five to ten times higher than that for somatic cells as donors and that cloned pups cannot be produced directly from cloned embryos derived from differentiated B and T cells or neuronal cells. The question remains as to whether SCNT-derived animal clones can be derived from truly differentiated somatic cells. We tested this hypothesis with mouse hematopoietic cells at different differentiation stages: hematopoietic stem cells, progenitor cells and granulocytes. We found that cloning efficiency increases over the differentiation hierarchy, and terminally differentiated postmitotic granulocytes yield cloned pups with the greatest cloning efficiency.

  19. Adipogenic differentiation and EGFP gene transfection of amniotic fluid-derived stem cells from goat fetus at terminal gestational age.

    Science.gov (United States)

    He, Xiao-Ying; Zheng, Yue-Mao; Qiu, Shuang; Qi, Ying-Pei; Zhang, Yong

    2011-08-01

    The aims of this study were to determine whether stem cells could be isolated from amniotic fluid of goat fetus at terminal gestational age and to determine if these stem cells could differentiate into adipogenic cells and be transfected with a reporter gene, EGFP (enhanced green fluorescent protein). The stem cells were isolated from amniotic fluid of goat fetus at terminal gestational age, induced to differentiate into adipogenic cells in vitro and transfected with the EGFP gene using lipofection. Markers associated with undifferentiated AFS (amniotic fluid-derived stem) cells were tested by RT (reverse transcription)-PCR. The results demonstrated that AFS cells could be isolated from amniotic fluid of goat fetus at terminal gestational age and could differentiate into adipogenic cells. The EGFP gene was transfected into AFS cells successfully. EGFP gene transfection efficiency of the three groups of transgenic AFS cells were 26.0, 29.9 and 30.5%, respectively. Both transgenic and wild-type AFS cells could express Hes1 (hairy and enhancer of split 1), Oct4 (octamer-binding protein 4) and Nanog.

  20. Calorie Restriction Attenuates Terminal Differentiation of Immune Cells.

    Science.gov (United States)

    White, Matthew J; Beaver, Charlotte M; Goodier, Martin R; Bottomley, Christian; Nielsen, Carolyn M; Wolf, Asia-Sophia F M; Boldrin, Luisa; Whitmore, Charlotte; Morgan, Jennifer; Pearce, Daniel J; Riley, Eleanor M

    2016-01-01

    Immune senescence is a natural consequence of aging and may contribute to frailty and loss of homeostasis in later life. Calorie restriction increases healthy life-span in C57BL/6J (but not DBA/2J) mice, but whether this is related to preservation of immune function, and how it interacts with aging, is unclear. We compared phenotypic and functional characteristics of natural killer (NK) cells and T cells, across the lifespan, of calorie-restricted (CR) and control C57BL/6 and DBA/2 mice. Calorie restriction preserves a naïve T cell phenotype and an immature NK cell phenotype as mice age. The splenic T cell populations of CR mice had higher proportions of CD11a - CD44 lo cells, lower expression of TRAIL, KLRG1, and CXCR3, and higher expression of CD127, compared to control mice. Similarly, splenic NK cells from CR mice had higher proportions of less differentiated CD11b - CD27 + cells and correspondingly lower proportions of highly differentiated CD11b + CD27 - NK cells. Within each of these subsets, cells from CR mice had higher expression of CD127, CD25, TRAIL, NKG2A/C/E, and CXCR3 and lower expression of KLRG1 and Ly49 receptors compared to controls. The effects of calorie restriction on lymphoid cell populations in lung, liver, and lymph nodes were identical to those seen in the spleen, indicating that this is a system-wide effect. The impact of calorie restriction on NK cell and T cell maturation is much more profound than the effect of aging and, indeed, calorie restriction attenuates these age-associated changes. Importantly, the effects of calorie restriction on lymphocyte maturation were more marked in C57BL/6 than in DBA/2J mice indicating that delayed lymphocyte maturation correlates with extended lifespan. These findings have implications for understanding the interaction between nutritional status, immunity, and healthy lifespan in aging populations.

  1. Investigation of efficient termination structure for improved breakdown properties of semiconductor radiation detectors

    International Nuclear Information System (INIS)

    Krizaj, D.; Resnik, D.; Vrtacnik, D.; Amon, S.

    1998-01-01

    Efficiency of a new junction termination structure for improvement of breakdown properties of semiconductor radiation detectors is investigated. The structure consists of a diffused resistor winding around the active junction in a spiral fashion. The current flow through the spiral enables controlled potential distribution along the spiral turns and thus controlled depletion spreading from the main junction, efficiently preventing premature avalanche breakdown. Both multiple guard-ring structures and spiral junction termination structures have shown good breakdown properties typically three to five times higher than breakdown voltages of diodes without junction termination. The breakdown voltages of spiral junction termination structures are only weakly influenced by changes in substrate doping concentration caused by neutron irradiation. They can thus be considered for termination of future semiconductor radiation detectors

  2. A Study on the Efficiency of Container Terminals in Korea and China

    Directory of Open Access Journals (Sweden)

    Xue Bin Zheng

    2016-12-01

    Full Text Available The objective of this study is to derive implications required for efficiency improvement and management level enhancement by selecting container terminals within major large ports of Korea and China as comparison units, evaluating their relative efficiencies and analyzing the trend of changes in their efficiencies. Since the scope of comparison subjects has been narrowed down to container terminals unlike previous studies, it is expected that the study results would have significant meaning due to the fact that it would be possible to compare and analyze in more detail. To achieve the objective, 30 major container terminals in both countries are selected, input and output variables are defined for each terminal and the DEA (data envelopment analysis model is used to conduct an analysis. The results show that the efficiency of major terminals in Korea (CCR: 0.815, BCC: 0.886 showed similar efficiency with China's terminals (CCR: 0.817, BCC: 0.887. While previous studies conclude that the efficiency of ports in Korea is far lower than that of ports in China.

  3. Grain intermodal terminals: evaluation of pure technical efficiency by Data Envelopment Analysis

    Directory of Open Access Journals (Sweden)

    Maria Gabriela Mendonça Peixoto

    Full Text Available Abstract This paper aimed to verify if terminals with productive efficiency also have pure technical efficiency, using DEA (Data Envelopment Analysis technique. The research approach was the qualitative-quantitative or mixed, with exploratory purpose; the research method defined was the case study (multicases; data were collected through interviews using a structured questionnaire and non-probability for convenience sampling. While the application of Charnes, Cooper and Rhodes (CCR model observed that only three (4, 7 and 11, of the twelve analyzed Decision Making Units (DMUs have total technical efficiency, through Banker, Charnes and Cooper (BCC model, it was possible to observe that these terminals were the only ones with pure technical efficiency. The three inefficient DMUs (1, 2 and 12 showed pure technical efficiency, suggesting that these terminals might present probable scale operations’ inefficiency, aspect not addressed in this paper.

  4. Efficient Estimating Functions for Stochastic Differential Equations

    DEFF Research Database (Denmark)

    Jakobsen, Nina Munkholt

    The overall topic of this thesis is approximate martingale estimating function-based estimationfor solutions of stochastic differential equations, sampled at high frequency. Focuslies on the asymptotic properties of the estimators. The first part of the thesis deals with diffusions observed over...

  5. Different requirements of functional telomeres in neural stem cells and terminally differentiated neurons.

    Science.gov (United States)

    Lobanova, Anastasia; She, Robert; Pieraut, Simon; Clapp, Charlie; Maximov, Anton; Denchi, Eros Lazzerini

    2017-04-01

    Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons. Conditional knockout of TRF2 in post-mitotic immature neurons had virtually no detectable effect on circuit assembly, neuronal gene expression, and the behavior of adult animals despite triggering massive end-to-end chromosome fusions across the brain. These results suggest that telomeres are dispensable in terminally differentiated neurons and provide mechanistic insight into cognitive abnormalities associated with aberrant telomere length in humans. © 2017 Lobanova et al.; Published by Cold Spring Harbor Laboratory Press.

  6. Differential BPFs with Multiple Transmission Zeros Based on Terminated Coupled Lines

    Science.gov (United States)

    Niu, Yiming; Yang, Guo; Wu, Wen

    2018-04-01

    Differential bandpass filters (BPFs) named Filter A and Filter B based on Terminated Coupled Lines (TCLs) are proposed in this letter. The TCLs contributes to not only three poles in differential-mode (DM) for wideband filtering response but also multiple zeros in both DM and common-mode (CM) offering wide DM out-of-band rejection and good CM suppression. Fabricated filters centred at 3.5 GHz with wide DM passband and wideband CM suppression have been designed and measured. The filters improved the noise suppression capability of the communication and radiometer systems. The simulated and measured results are in good agreement.

  7. Donor cell differentiation, reprogramming, and cloning efficiency: elusive or illusive correlation?

    Science.gov (United States)

    Oback, B; Wells, D N

    2007-05-01

    Compared to other assisted reproductive technologies, mammalian nuclear transfer (NT) cloning is inefficient in generating viable offspring. It has been postulated that nuclear reprogramming and cloning efficiency can be increased by choosing less differentiated cell types as nuclear donors. This hypothesis is mainly supported by comparative mouse cloning experiments using early blastomeres, embryonic stem (ES) cells, and terminally differentiated somatic donor cells. We have re-evaluated these comparisons, taking into account different NT procedures, the use of donor cells from different genetic backgrounds, sex, cell cycle stages, and the lack of robust statistical significance when post-blastocyst development is compared. We argue that while the reprogrammability of early blastomeres appears to be much higher than that of somatic cells, it has so far not been conclusively determined whether differentiation status affects cloning efficiency within somatic donor cell lineages. Copyright (c) 2006 Wiley-Liss, Inc.

  8. Efficient Estimating Functions for Stochastic Differential Equations

    DEFF Research Database (Denmark)

    Jakobsen, Nina Munkholt

    The overall topic of this thesis is approximate martingale estimating function-based estimationfor solutions of stochastic differential equations, sampled at high frequency. Focuslies on the asymptotic properties of the estimators. The first part of the thesis deals with diffusions observed over...... a fixed time interval. Rate optimal and effcient estimators areobtained for a one-dimensional diffusion parameter. Stable convergence in distribution isused to achieve a practically applicable Gaussian limit distribution for suitably normalisedestimators. In a simulation example, the limit distributions...... multidimensional parameter. Conditions for rate optimality and effciency of estimatorsof drift-jump and diffusion parameters are given in some special cases. Theseconditions are found to extend the pre-existing conditions applicable to continuous diffusions,and impose much stronger requirements on the estimating...

  9. Quantum Coherent Three-Terminal Thermoelectrics: Maximum Efficiency at Given Power Output

    Directory of Open Access Journals (Sweden)

    Robert S. Whitney

    2016-05-01

    Full Text Available This work considers the nonlinear scattering theory for three-terminal thermoelectric devices used for power generation or refrigeration. Such systems are quantum phase-coherent versions of a thermocouple, and the theory applies to systems in which interactions can be treated at a mean-field level. It considers an arbitrary three-terminal system in any external magnetic field, including systems with broken time-reversal symmetry, such as chiral thermoelectrics, as well as systems in which the magnetic field plays no role. It is shown that the upper bound on efficiency at given power output is of quantum origin and is stricter than Carnot’s bound. The bound is exactly the same as previously found for two-terminal devices and can be achieved by three-terminal systems with or without broken time-reversal symmetry, i.e., chiral and non-chiral thermoelectrics.

  10. Efficient receiver tuning using differential evolution strategies

    Science.gov (United States)

    Wheeler, Caleb H.; Toland, Trevor G.

    2016-08-01

    Differential evolution (DE) is a powerful and computationally inexpensive optimization strategy that can be used to search an entire parameter space or to converge quickly on a solution. The Kilopixel Array Pathfinder Project (KAPPa) is a heterodyne receiver system delivering 5 GHz of instantaneous bandwidth in the tuning range of 645-695 GHz. The fully automated KAPPa receiver test system finds optimal receiver tuning using performance feedback and DE. We present an adaptation of DE for use in rapid receiver characterization. The KAPPa DE algorithm is written in Python 2.7 and is fully integrated with the KAPPa instrument control, data processing, and visualization code. KAPPa develops the technologies needed to realize heterodyne focal plane arrays containing 1000 pixels. Finding optimal receiver tuning by investigating large parameter spaces is one of many challenges facing the characterization phase of KAPPa. This is a difficult task via by-hand techniques. Characterizing or tuning in an automated fashion without need for human intervention is desirable for future large scale arrays. While many optimization strategies exist, DE is ideal for time and performance constraints because it can be set to converge to a solution rapidly with minimal computational overhead. We discuss how DE is utilized in the KAPPa system and discuss its performance and look toward the future of 1000 pixel array receivers and consider how the KAPPa DE system might be applied.

  11. An Efficient Series Solution for Nonlinear Multiterm Fractional Differential Equations

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    Moh’d Khier Al-Srihin

    2017-01-01

    Full Text Available In this paper, we introduce an efficient series solution for a class of nonlinear multiterm fractional differential equations of Caputo type. The approach is a generalization to our recent work for single fractional differential equations. We extend the idea of the Taylor series expansion method to multiterm fractional differential equations, where we overcome the difficulty of computing iterated fractional derivatives, which are difficult to be computed in general. The terms of the series are obtained sequentially using a closed formula, where only integer derivatives have to be computed. Several examples are presented to illustrate the efficiency of the new approach and comparison with the Adomian decomposition method is performed.

  12. Development programme update for a socket solution offering a highly efficient termination of polyester mooring tethers

    International Nuclear Information System (INIS)

    Firth, Kevin M.; Calverley, Steve; Quintas, Manuel Pedro

    2000-01-01

    Bridon have previously developed a patented 'Socket and Spike' design for polyester tethers comprising a parallel array of seven sub-ropes. This phase of the development was successfully completed, subsequently Bridon have embarked on a new phase which aims to increase the efficiency of the socket and address the assembly problems that have been identified. The development has continued with the 'Socket and Spike' principle but a unique termination method has been devised such that each sub-rope is terminated in it is own mini-socket and pre-loaded prior to fitting into the main socket ensuring zero slippage and equal transfer of the mooring load. The sub-ropes are nested into the main socket body resulting in a socket termination that lighter, more efficient and easier to handle than the current method of spliced eye incorporating a steel spool and shackle. (author)

  13. SHP2 regulates chondrocyte terminal differentiation, growth plate architecture and skeletal cell fates.

    Directory of Open Access Journals (Sweden)

    Margot E Bowen

    Full Text Available Loss of PTPN11/SHP2 in mice or in human metachondromatosis (MC patients causes benign cartilage tumors on the bone surface (exostoses and within bones (enchondromas. To elucidate the mechanisms underlying cartilage tumor formation, we investigated the role of SHP2 in the specification, maturation and organization of chondrocytes. Firstly, we studied chondrocyte maturation by performing RNA-seq on primary chondrocyte pellet cultures. We found that SHP2 depletion, or inhibition of the ERK1/2 pathway, delays the terminal differentiation of chondrocytes from the early-hypertrophic to the late-hypertrophic stage. Secondly, we studied chondrocyte maturation and organization in mice with a mosaic postnatal inactivation of Ptpn11 in chondrocytes. We found that the vertebral growth plates of these mice have expanded domains of early-hypertrophic chondrocytes that have not yet terminally differentiated, and their enchondroma-like lesions arise from chondrocytes displaced from the growth plate due to a disruption in the organization of maturation and ossification zones. Furthermore, we observed that lesions from human MC patients also display disorganized chondrocyte maturation zones. Next, we found that inactivation of Ptpn11 in Fsp1-Cre-expressing fibroblasts induces exostosis-like outgrowths, suggesting that loss of SHP2 in cells on the bone surface and at bone-ligament attachment sites induces ectopic chondrogenesis. Finally, we performed lineage tracing to show that exostoses and enchondromas in mice likely contain mixtures of wild-type and SHP2-deficient chondrocytes. Together, these data indicate that in patients with MC, who are heterozygous for inherited PTPN11 loss-of-function mutations, second-hit mutations in PTPN11 can induce enchondromas by disrupting the organization and delaying the terminal differentiation of growth plate chondrocytes, and can induce exostoses by causing ectopic chondrogenesis of cells on the bone surface. Furthermore, the

  14. Differential theory of learning for efficient neural network pattern recognition

    Science.gov (United States)

    Hampshire, John B., II; Vijaya Kumar, Bhagavatula

    1993-09-01

    We describe a new theory of differential learning by which a broad family of pattern classifiers (including many well-known neural network paradigms) can learn stochastic concepts efficiently. We describe the relationship between a classifier's ability to generate well to unseen test examples and the efficiency of the strategy by which it learns. We list a series of proofs that differential learning is efficient in its information and computational resource requirements, whereas traditional probabilistic learning strategies are not. The proofs are illustrated by a simple example that lends itself to closed-form analysis. We conclude with an optical character recognition task for which three different types of differentially generated classifiers generalize significantly better than their probabilistically generated counterparts.

  15. A function for Rac1 in the terminal differentiation and pigmentation of hair

    DEFF Research Database (Denmark)

    Behrendt, Kristina; Klatte, Jennifer; Pofahl, Ruth

    2012-01-01

    in the regulation of terminal hair follicle differentiation. To address this, we have expressed a constitutively active mutant of Rac1, L61Rac1, only in the basal epidermal layer and outer root sheath of mice possessing an epidermis-specific deletion of endogenous Rac1, which experience severe hair loss......The small GTPase Rac1 is ubiquitously expressed in proliferating and differentiating layers of the epidermis and hair follicles. Previously, Rac1 was shown to regulate stem cell behaviour in these compartments. We have asked whether Rac1 has, in addition, a specific, stem-cell-independent function....... The resulting 'rescue' mice exhibited a hair coat throughout their lives. Therefore, expression of Rac1 activity in the keratin-14-positive compartment of the skin is sufficient for the formation of hair follicles and hair in normal quantities. The quality of hair formed in rescue mice was, however, not normal...

  16. SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells

    Energy Technology Data Exchange (ETDEWEB)

    Noah, Taeko K.; Kazanjian, Avedis [Gastroenterology, Hepatology and Nutrition, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Whitsett, Jeffrey [Developmental Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Neonatology and Pulmonary Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Shroyer, Noah F., E-mail: noah.shroyer@cchmc.org [Gastroenterology, Hepatology and Nutrition, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Developmental Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States)

    2010-02-01

    Background and Aims: SPDEF (also termed PDEF or PSE) is an ETS family transcription factor that regulates gene expression in the prostate and goblet cell hyperplasia in the lung. Spdef has been reported to be expressed in the intestine. In this paper, we identify an important role for Spdef in regulating intestinal epithelial cell homeostasis and differentiation. Methods: SPDEF expression was inhibited in colon cancer cells to determine its ability to control goblet cell gene activation. The effects of transgenic expression of Spdef on intestinal differentiation and homeostasis were determined. Results: In LS174T colon cancer cells treated with Notch/{gamma}-secretase inhibitor to activate goblet cell gene expression, shRNAs that inhibited SPDEF also repressed expression of goblet cell genes AGR2, MUC2, RETLNB, and SPINK4. Transgenic expression of Spdef caused the expansion of intestinal goblet cells and corresponding reduction in Paneth, enteroendocrine, and absorptive enterocytes. Spdef inhibited proliferation of intestinal crypt cells without induction of apoptosis. Prolonged expression of the Spdef transgene caused a progressive reduction in the number of crypts that expressed Spdef, consistent with its inhibitory effects on cell proliferation. Conclusions: Spdef was sufficient to inhibit proliferation of intestinal progenitors and induce differentiation into goblet cells; SPDEF was required for activation of goblet cell associated genes in vitro. These data support a model in which Spdef promotes terminal differentiation into goblet cells of a common goblet/Paneth progenitor.

  17. [Stimulation of maturing and terminal differentiation by concanavalin A in rabbit permanent chondrocyte cultures].

    Science.gov (United States)

    Yan, W Q; Yang, T S; Hou, L Z; Susuki, F; Kato, Y

    1994-12-01

    The effect of concanavalin A (Con A) on maturing and terminal differentiation in permanent chondrocyte cultures were examined. Chondrocytes isolated from permanent cartilage were seeded at low density and grown in MEM medium containing 10% fetal bovine serum, 50 micrograms/ml of ascorbic acid and antibiotics, at 37 degrees C under 50% CO2 in air. At 0.3% of low serum concentration, addition of Con A to the culture medium increased by 3- to 4-fold the incorporation of [35S] sulfate into large chondroitin sulfate proteoglycan that characteristically found in cartilage. Chemical analysis showed a 4-fold increase in the accumulation of macromolecular containing hexuronic acid in Con A-maintained cultures. The effect of Con A on [35S]sulfate incorporation into proteoglycan was greater than that of various growth factor or hormones. Brief exposure of the permanent chondrocytes to Con A (5 micrograms/ml) for 24 hours and subsequent incubation in its absence for 5-10 days resulted in 10- to 100-fold increase in alkaline phosphatase and binding of 1.25 (OH)2 vitamin D3 to cells. Treatment with Con A also resulted in 10- to 20-fold increase in calcium content and 45Ca incorporation into insoluble material. Methyl-D-mannopyranoside reversed the effect of Con A on [35S]sulfate incorporation into proteoglycan and alkaline phosphatase activity. Since other lectins, such as wheat germ agglutinin, lentil lectin, phytohemagglutinin, Ulex europeasu agglutinin and garden pea lectin had been tested to have little effect on [35S]sulfate incorporation into proteoglycans and induction of alkaline phosphatase activity, the Con A action on chondrocytes seems specific. These results indicate that Con A is a potent modulator of differentiation of chondrocytes, which induces the onset on a maturing and a terminal differentiation in chondrocytes, leading to extensive calcification of the extracellular matrix.

  18. Tfe3 expression is closely associated to macrophage terminal differentiation of human hematopoietic myeloid precursors

    International Nuclear Information System (INIS)

    Zanocco-Marani, Tommaso; Vignudelli, Tatiana; Gemelli, Claudia; Pirondi, Sara; Testa, Anna; Montanari, Monica; Parenti, Sandra; Tenedini, Elena; Grande, Alexis; Ferrari, Sergio

    2006-01-01

    The MItf-Tfe family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors encodes four family members: MItf, Tfe3, TfeB and TfeC. In vitro, each protein of the family binds DNA in a homo- or heterodimeric form with other family members. Tfe3 is involved in chromosomal translocations recurrent in different tumors and it has been demonstrated, by in vivo studies, that it plays, redundantly with MItf, an important role in the process of osteoclast formation, in particular during the transition from mono-nucleated to multi-nucleated osteoclasts. Since mono-nucleated osteoclasts derive from macrophages we investigated whether Tfe3 might play a role upstream during hematopoietic differentiation. Here we show that Tfe3 is able to induce mono-macrophagic differentiation of U937 cells, in association with a decrease of cell proliferation and an increase of apoptosis. We also show that Tfe3 does not act physiologically during commitment of CD34+ hematopoietic stem cells (HSCs), since it is not able to direct HSCs toward a specific lineage as observed by clonogenic assay, but is a strong actor of terminal differentiation since it allows human primary myeloblasts' maturation toward the macrophage lineage

  19. Efficient spin filter using multi-terminal quantum dot with spin-orbit interaction

    Directory of Open Access Journals (Sweden)

    Yokoyama Tomohiro

    2011-01-01

    Full Text Available Abstract We propose a multi-terminal spin filter using a quantum dot with spin-orbit interaction. First, we formulate the spin Hall effect (SHE in a quantum dot connected to three leads. We show that the SHE is significantly enhanced by the resonant tunneling if the level spacing in the quantum dot is smaller than the level broadening. We stress that the SHE is tunable by changing the tunnel coupling to the third lead. Next, we perform a numerical simulation for a multi-terminal spin filter using a quantum dot fabricated on semiconductor heterostructures. The spin filter shows an efficiency of more than 50% when the conditions for the enhanced SHE are satisfied. PACS numbers: 72.25.Dc,71.70.Ej,73.63.Kv,85.75.-d

  20. Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation

    DEFF Research Database (Denmark)

    Zebrowski, David C.; Jensen, Charlotte H.; Becker, Robert

    2017-01-01

    exhibited midbody formation consistent with successful abscission, whereas those from 3 day-old cardiomyocytes after apical resection exhibited midbody formation consistent with abscission failure. Lastly, injured hearts failed to fully regenerate as evidenced by persistent scarring and reduced wall motion......After birth cardiomyocytes undergo terminal differentiation, characterized by binucleation and centrosome disassembly, rendering the heart unable to regenerate. Yet, it has been suggested that newborn mammals regenerate their hearts after apical resection by cardiomyocyte proliferation. Thus, we...... increased rate of binucleation there was a nearly 2-fold increase in the number of cardiomyocytes in mitosis indicating that the majority of injury-induced cardiomyocyte cell cycle activity results in binucleation, not proliferation. Concurrently, cardiomyocytes undergoing cytokinesis from embryonic hearts...

  1. Glucose-ABL1-TOR Signaling Modulates Cell Cycle Tuning to Control Terminal Appressorial Cell Differentiation.

    Science.gov (United States)

    Marroquin-Guzman, Margarita; Sun, Guangchao; Wilson, Richard A

    2017-01-01

    The conserved target of rapamycin (TOR) pathway integrates growth and development with available nutrients, but how cellular glucose controls TOR function and signaling is poorly understood. Here, we provide functional evidence from the devastating rice blast fungus Magnaporthe oryzae that glucose can mediate TOR activity via the product of a novel carbon-responsive gene, ABL1, in order to tune cell cycle progression during infection-related development. Under nutrient-free conditions, wild type (WT) M. oryzae strains form terminal plant-infecting cells (appressoria) at the tips of germ tubes emerging from three-celled spores (conidia). WT appressorial development is accompanied by one round of mitosis followed by autophagic cell death of the conidium. In contrast, Δabl1 mutant strains undergo multiple rounds of accelerated mitosis in elongated germ tubes, produce few appressoria, and are abolished for autophagy. Treating WT spores with glucose or 2-deoxyglucose phenocopied Δabl1. Inactivating TOR in Δabl1 mutants or glucose-treated WT strains restored appressorium formation by promoting mitotic arrest at G1/G0 via an appressorium- and autophagy-inducing cell cycle delay at G2/M. Collectively, this work uncovers a novel glucose-ABL1-TOR signaling axis and shows it engages two metabolic checkpoints in order to modulate cell cycle tuning and mediate terminal appressorial cell differentiation. We thus provide new molecular insights into TOR regulation and cell development in response to glucose.

  2. Constitutive β-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Quanwei; Chen, Sixu; Qin, Hao [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China); Feng, Jianquan [Department of Biomedical Sciences, Baylor College of Dentistry, Texas A& M Health Science Center, Dallas, TX 75246 (United States); Liu, Huayu; Liu, Daocheng; Li, Ang; Shen, Yue; Zhong, Xiaozheng; Li, Junfeng [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China); Zong, Zhaowen, E-mail: zongzhaowen@sina.cn [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China)

    2017-01-01

    Accumulating evidence suggests that Wnt/β-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of β-catenin (CA-β-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-β-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-β-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-β-catenin mice. Then the effect of CA-β-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-β-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-β-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-β-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-β-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-β-catenin mice. In summary, osteoblastic CA-β-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength. - Highlights: • Wnt/β-catenin signaling plays a central role in controlling bone mass. • CA-β-catenin has side effects on the bone

  3. Four-Terminal All-Perovskite Tandem Solar Cells Achieving Power Conversion Efficiencies Exceeding 23%

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Kai [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Zhao, Dewei [University of Toledo; Wang, Changlei [University of Toledo; Wuhan University; Song, Zhaoning [University of Toledo; Yu, Yue [University of Toledo; Chen, Cong [University of Toledo; Zhao, Xingzhong [Wuhan University; Yan, Yanfa [University of Toledo

    2018-02-09

    We report on fabrication of 4-terminal all-perovskite tandem solar cells with power conversion efficiencies exceeding 23% by mechanically stacking semitransparent 1.75 eV wide-bandgap FA0.8Cs0.2Pb(I0.7Br0.3)3 perovskite top cells with 1.25 eV low-bandgap (FASnI3)0.6(MAPbI3)0.4 bottom cells. The top cells use MoOx/ITO transparent electrodes and achieve transmittance up to 70% beyond 700 nm.

  4. Community effect triggers terminal differentiation of myogenic cells derived from muscle satellite cells by quenching Smad signaling

    Energy Technology Data Exchange (ETDEWEB)

    Yanagisawa, Michiko [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan); Aging Research, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550 (Japan); Mukai, Atsushi; Shiomi, Kosuke [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan); Song, Si-Yong [Institute of Neuroscience, Faculty of Pharmaceutical Sciences at Kagawa, Tokushima Bunri University, 1314-1 Shido, Sanuki-shi, Kagawa 769-2193 (Japan); Hashimoto, Naohiro, E-mail: nao@ncgg.go.jp [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan)

    2011-01-15

    A high concentration of bone morphogenetic proteins (BMPs) stimulates myogenic progenitor cells to undergo heterotopic osteogenic differentiation. However, the physiological role of the Smad signaling pathway during terminal muscle differentiation has not been resolved. We report here that Smad1/5/8 was phosphorylated and activated in undifferentiated growing mouse myogenic progenitor Ric10 cells without exposure to any exogenous BMPs. The amount of phosphorylated Smad1/5/8 was severely reduced during precocious myogenic differentiation under the high cell density culture condition even in growth medium supplemented with a high concentration of serum. Inhibition of the Smad signaling pathway by dorsomorphin, an inhibitor of Smad activation, or noggin, a specific antagonist of BMP, induced precocious terminal differentiation of myogenic progenitor cells in a cell density-dependent fashion even in growth medium. In addition, Smad1/5/8 was transiently activated in proliferating myogenic progenitor cells during muscle regeneration in rats. The present results indicate that the Smad signaling pathway is involved in a critical switch between growth and differentiation of myogenic progenitor cells both in vitro and in vivo. Furthermore, precocious cell density-dependent myogenic differentiation suggests that a community effect triggers the terminal muscle differentiation of myogenic cells by quenching the Smad signaling.

  5. Community effect triggers terminal differentiation of myogenic cells derived from muscle satellite cells by quenching Smad signaling

    International Nuclear Information System (INIS)

    Yanagisawa, Michiko; Mukai, Atsushi; Shiomi, Kosuke; Song, Si-Yong; Hashimoto, Naohiro

    2011-01-01

    A high concentration of bone morphogenetic proteins (BMPs) stimulates myogenic progenitor cells to undergo heterotopic osteogenic differentiation. However, the physiological role of the Smad signaling pathway during terminal muscle differentiation has not been resolved. We report here that Smad1/5/8 was phosphorylated and activated in undifferentiated growing mouse myogenic progenitor Ric10 cells without exposure to any exogenous BMPs. The amount of phosphorylated Smad1/5/8 was severely reduced during precocious myogenic differentiation under the high cell density culture condition even in growth medium supplemented with a high concentration of serum. Inhibition of the Smad signaling pathway by dorsomorphin, an inhibitor of Smad activation, or noggin, a specific antagonist of BMP, induced precocious terminal differentiation of myogenic progenitor cells in a cell density-dependent fashion even in growth medium. In addition, Smad1/5/8 was transiently activated in proliferating myogenic progenitor cells during muscle regeneration in rats. The present results indicate that the Smad signaling pathway is involved in a critical switch between growth and differentiation of myogenic progenitor cells both in vitro and in vivo. Furthermore, precocious cell density-dependent myogenic differentiation suggests that a community effect triggers the terminal muscle differentiation of myogenic cells by quenching the Smad signaling.

  6. Differential Tus-Ter binding and lock formation: implications for DNA replication termination in Escherichia coli.

    Science.gov (United States)

    Moreau, Morgane J J; Schaeffer, Patrick M

    2012-10-01

    In E. coli, DNA replication termination occurs at Ter sites and is mediated by Tus. Two clusters of five Ter sites are located on each side of the terminus region and constrain replication forks in a polar manner. The polarity is due to the formation of the Tus-Ter-lock intermediate. Recently, it has been shown that DnaB helicase which unwinds DNA at the replication fork is preferentially stopped at the non-permissive face of a Tus-Ter complex without formation of the Tus-Ter-lock and that fork pausing efficiency is sequence dependent, raising two essential questions: Does the affinity of Tus for the different Ter sites correlate with fork pausing efficiency? Is formation of the Tus-Ter-lock the key factor in fork pausing? The combined use of surface plasmon resonance and GFP-Basta showed that Tus binds strongly to TerA-E and G, moderately to TerH-J and weakly to TerF. Out of these ten Ter sites only two, TerF and H, were not able to form significant Tus-Ter-locks. Finally, Tus's resistance to dissociation from Ter sites and the strength of the Tus-Ter-locks correlate with the differences in fork pausing efficiency observed for the different Ter sites by Duggin and Bell (2009).

  7. Three-terminal heterojunction bipolar transistor solar cell for high-efficiency photovoltaic conversion.

    Science.gov (United States)

    Martí, A; Luque, A

    2015-04-22

    Here we propose, for the first time, a solar cell characterized by a semiconductor transistor structure (n/p/n or p/n/p) where the base-emitter junction is made of a high-bandgap semiconductor and the collector is made of a low-bandgap semiconductor. We calculate its detailed-balance efficiency limit and prove that it is the same one than that of a double-junction solar cell. The practical importance of this result relies on the simplicity of the structure that reduces the number of layers that are required to match the limiting efficiency of dual-junction solar cells without using tunnel junctions. The device naturally emerges as a three-terminal solar cell and can also be used as building block of multijunction solar cells with an increased number of junctions.

  8. Efficient differentiation of human embryonic stem cells to definitive endoderm.

    Science.gov (United States)

    D'Amour, Kevin A; Agulnick, Alan D; Eliazer, Susan; Kelly, Olivia G; Kroon, Evert; Baetge, Emmanuel E

    2005-12-01

    The potential of human embryonic stem (hES) cells to differentiate into cell types of a variety of organs has generated much excitement over the possible use of hES cells in therapeutic applications. Of great interest are organs derived from definitive endoderm, such as the pancreas. We have focused on directing hES cells to the definitive endoderm lineage as this step is a prerequisite for efficient differentiation to mature endoderm derivatives. Differentiation of hES cells in the presence of activin A and low serum produced cultures consisting of up to 80% definitive endoderm cells. This population was further enriched to near homogeneity using the cell-surface receptor CXCR4. The process of definitive endoderm formation in differentiating hES cell cultures includes an apparent epithelial-to-mesenchymal transition and a dynamic gene expression profile that are reminiscent of vertebrate gastrulation. These findings may facilitate the use of hES cells for therapeutic purposes and as in vitro models of development.

  9. An Efficient Binary Differential Evolution with Parameter Adaptation

    Directory of Open Access Journals (Sweden)

    Dongli Jia

    2013-04-01

    Full Text Available Differential Evolution (DE has been applied to many scientific and engineering problems for its simplicity and efficiency. However, the standard DE cannot be used in a binary search space directly. This paper proposes an adaptive binary Differential Evolution algorithm, or ABDE, that has a similar framework as the standard DE but with an improved binary mutation strategy in which the best individual participates. To further enhance the search ability, the parameters of the ABDE are slightly disturbed in an adaptive manner. Experiments have been carried out by comparing ABDE with two binary DE variants, normDE and BDE, and the most used binary search technique, GA, on a set of 13 selected benchmark functions and the classical 0-1 knapsack problem. Results show that the ABDE performs better than, or at least comparable to, the other algorithms in terms of search ability, convergence speed, and solution accuracy.

  10. Differential electricity pricing and energy efficiency in South Africa

    International Nuclear Information System (INIS)

    Kohler, Marcel

    2014-01-01

    By international standards the economy of South Africa is extremely energy intensive with only a few countries having higher intensities. SA's primary energy use per unit of GDP is amongst the highest in the world. The high energy and electricity intensity of the economy partly reflects SA's resource endowments (in particular the abundance of coal) but is also a function of the historical under-pricing of coal and electricity by the authorities. South African mining and industrial electricity efficiency is particularly concerning and considerably lower than the global average. This paper sets out to fill a significant gap in the South African energy literature by highlighting the importance of incorporating electricity demand factors as part of the country's energy policy and electricity planning horizon. The paper focuses its attention on modelling the electricity consumption of SA's industrial and mining sectors given these account for the lion's share of electricity demand. A differential electricity pricing policy which targets electricity intensive industrial and mining activities (as practised in China since 2004) is viewed by the author to be a superior policy to blanket electricity price increases administered by authorities in an effort to encourage electricity savings and improve energy efficiency in South Africa. - Highlights: • SA's primary energy use per unit of GDP is amongst the highest in the world. • SA industrial electricity efficiency is considerably lower than the global average. • A differential electricity pricing policy which targets electricity intensive activities. • Differential tariffs raise the cost of energy inefficiency and induces energy saving. • Highlights importance of energy demand modelling in electricity supply planning

  11. Impaired terminal differentiation of hippocampal granule neurons and defective contextual memory in PC3/Tis21 knockout mice.

    Directory of Open Access Journals (Sweden)

    Stefano Farioli-Vecchioli

    Full Text Available Neurogenesis in the dentate gyrus of the adult hippocampus has been implicated in neural plasticity and memory, but the molecular mechanisms controlling the proliferation and differentiation of newborn neurons and their integration into the synaptic circuitry are still largely unknown. To investigate this issue, we have analyzed the adult hippocampal neurogenesis in a PC3/Tis21-null mouse model. PC3/Tis21 is a transcriptional co-factor endowed with antiproliferative and prodifferentiative properties; indeed, its upregulation in neural progenitors has been shown to induce exit from cell cycle and differentiation. We demonstrate here that the deletion of PC3/Tis21 causes an increased proliferation of progenitor cells in the adult dentate gyrus and an arrest of their terminal differentiation. In fact, in the PC3/Tis21-null hippocampus postmitotic undifferentiated neurons accumulated, while the number of terminally differentiated neurons decreased of 40%. As a result, PC3/Tis21-null mice displayed a deficit of contextual memory. Notably, we observed that PC3/Tis21 can associate to the promoter of Id3, an inhibitor of proneural gene activity, and negatively regulates its expression, indicating that PC3/Tis21 acts upstream of Id3. Our results identify PC3/Tis21 as a gene required in the control of proliferation and terminal differentiation of newborn neurons during adult hippocampal neurogenesis and suggest its involvement in the formation of contextual memories.

  12. Development of High Efficiency Four-Terminal Perovskite-Silicon Tandems

    Science.gov (United States)

    Duong, The Duc

    This thesis is concerned with the development of high efficiency four-terminal perovskite-silicon tandem solar cells with the potential to reduce the cost of solar energy. The work focuses on perovskite top cells and can be divided into three main parts: developing low parasitic absorption and efficient semi-transparent perovskite cells, doping perovskite materials with rubidium, and optimizing perovskite material's bandgap with quadruple-cation and mixed-halide. A further section investigates the light stability of optimized bandgap perovskite cells. In a four-terminal mechanically stacked tandem, the perovskite top cell requires two transparent contacts at both the front and rear sides. Through detailed optical and electrical power loss analysis of the tandem efficiency due to non-ideal properties of the two transparent contacts, optimal contact parameters in term of sheet resistance and transparency are identified. Indium doped tin oxide by sputtering is used for both two transparent contacts and their deposition parameters are optimized separately. The semi-transparent perovskite cell using MAPbI3 has an efficiency of more than 12% with less than 12% parasitic absorption and up to 80% transparency in the long wavelength region. Using a textured foil as anti-reflection coating, an outstanding average transparency of 84% in the long wavelength is obtained. The low parasitic absorption allows an opaque version of the semi-transparent perovskite cell to operate efficiently in a filterless spectrum splitting perovskite-silicon tandem configuration. To further enhance the performance of perovskite cells, it is essential to improve the quality of perovskite films. This can be achieved with mixed-perovskite FAPbI3/MAPbBr3. However, mixed-perovskite films normally contain small a small amount of a non-perovskite phase, which is detrimental for the cell performance. Rb-doping is found to eliminate the formation of the non-perovskite phase and enhance the crystallinity of

  13. The differential method for grating efficiencies implemented in mathematica

    Energy Technology Data Exchange (ETDEWEB)

    Valdes, V.; McKinney, W. [Lawrence Berkeley Lab., CA (United States); Palmer, C. [Milton Co., Rochester, NY (United States). Roy Analytical Products Div.

    1993-08-01

    In order to facilitate the accurate calculation of diffraction grating efficiencies in the soft x-ray region, we have implemented the differential method of Neviere and Vincent in Mathematica [1]. This simplifies the programming to maximize the transparency of the theory for the user. We alleviate some of the overhead burden of the Mathematica program by coding the time-consuming numerical integration in C subprograms. We recall the differential method directly from Maxwell`s equations. The pseudo-periodicity of the grating profile and the electromagnetic fields allows us to use their Fourier series expansions to formulate an infinite set of coupled differential equations. A finite subset of the equations are then numerically integrated using the Numerov method for the transverse electric (TE) case and a fourth-order Runge-Kutta algorithm for the transverse magnetic (TM) case. We have tested our program by comparisons with the scalar theory and with published theoretical results for the blazed, sinusoidal and square wave profiles. The Reciprocity Theorem has also been used as a means to verify the method. We have found it to be verified for several cases to within the computational accuracy of the method.

  14. An Efficient Genetic Algorithm to Solve the Intermodal Terminal Location problem

    Directory of Open Access Journals (Sweden)

    Mustapha Oudani

    2014-11-01

    Full Text Available The exponential growth of the flow of goods and passengers, fragility of certain products and the need for the optimization of transport costs impose on carriers to use more and more multimodal transport. In addition, the need for intermodal transport policy has been strongly driven by environmental concerns and to benefit from the combination of different modes of transport to cope with the increased economic competition. This research is mainly concerned with the Intermodal Terminal Location Problem introduced recently in scientific literature which consists to determine a set of potential sites to open and how to route requests to a set of customers through the network while minimizing the total cost of transportation. We begin by presenting a description of the problem. Then, we present a mathematical formulation of the problem and discuss the sense of its constraints. The objective function to minimize is the sum of road costs and railroad combined transportation costs. As the Intermodal Terminal Location Problemproblem is NP-hard, we propose an efficient real coded genetic algorithm for solving the problem. Our solutions are compared to CPLEX and also to the heuristics reported in the literature. Numerical results show that our approach outperforms the other approaches.

  15. Energy-efficient WDM-OFDM-PON employing shared OFDM modulation modules in optical line terminal.

    Science.gov (United States)

    Hu, Xiaofeng; Zhang, Liang; Cao, Pan; Wang, Kongtao; Su, Yikai

    2012-03-26

    We propose and experimentally demonstrate a scheme to improve the energy efficiency of wavelength division multiplexing - orthogonal frequency division multiplexing - passive optical networks (WDM-OFDM-PONs). By using an N × M opto-mechanic switch in optical line terminal (OLT), an OFDM modulation module is shared by several channels to deliver data to multiple users with low traffic demands during non-peak hours of the day, thus greatly reducing the number of operating devices and minimizing the energy consumption of the OLT. An experiment utilizing one OFDM modulation module to serve three optical network units (ONUs) in a WDM-OFDM-PON is performed to verify the feasibility of our proposal. Theoretical analysis and numerical calculation show that the proposed scheme can achieve a saving of 23.6% in the energy consumption of the OFDM modulation modules compared to conventional WDM-OFDM-PON.

  16. III-V-on-silicon solar cells reaching 33% photoconversion efficiency in two-terminal configuration

    Science.gov (United States)

    Cariou, Romain; Benick, Jan; Feldmann, Frank; Höhn, Oliver; Hauser, Hubert; Beutel, Paul; Razek, Nasser; Wimplinger, Markus; Bläsi, Benedikt; Lackner, David; Hermle, Martin; Siefer, Gerald; Glunz, Stefan W.; Bett, Andreas W.; Dimroth, Frank

    2018-04-01

    Silicon dominates the photovoltaic industry but the conversion efficiency of silicon single-junction solar cells is intrinsically constrained to 29.4%, and practically limited to around 27%. It is possible to overcome this limit by combining silicon with high-bandgap materials, such as III-V semiconductors, in a multi-junction device. Significant challenges associated with this material combination have hindered the development of highly efficient III-V/Si solar cells. Here, we demonstrate a III-V/Si cell reaching similar performances to standard III-V/Ge triple-junction solar cells. This device is fabricated using wafer bonding to permanently join a GaInP/GaAs top cell with a silicon bottom cell. The key issues of III-V/Si interface recombination and silicon's weak absorption are addressed using poly-silicon/SiOx passivating contacts and a novel rear-side diffraction grating for the silicon bottom cell. With these combined features, we demonstrate a two-terminal GaInP/GaAs//Si solar cell reaching a 1-sun AM1.5G conversion efficiency of 33.3%.

  17. miR-24-mediated down-regulation of H2AX suppresses DNA repair in terminally differentiated blood cells

    Science.gov (United States)

    Lal, Ashish; Pan, Yunfeng; Navarro, Francisco; Dykxhoorn, Derek M.; Moreau, Lisa; Meire, Eti; Bentwich, Zvi; Lieberman, Judy; Chowdhury, Dipanjan

    2010-01-01

    Terminally differentiated cells have reduced capacity to repair double strand breaks (DSB), but the molecular mechanism behind this down-regulation is unclear. Here we find that miR-24 is consistently up-regulated during post-mitotic differentiation of hematopoietic cell lines and regulates the histone variant H2AX, a key DSB repair protein that activates cell cycle checkpoint proteins and retains DSB repair factors at DSB foci. The H2AX 3’UTR contains conserved miR-24 binding sites regulated by miR-24. Both H2AX mRNA and protein are substantially reduced during hematopoietic cell terminal differentiation by miR-24 up-regulation both in in vitro differentiated cells and primary human blood cells. miR-24 suppression of H2AX renders cells hypersensitive to γ-irradiation and genotoxic drugs. Antagonizing miR-24 in differentiating cells protects them from DNA damage-induced cell death, while transfecting miR-24 mimics in dividing cells increases chromosomal breaks and unrepaired DNA damage and reduces viability in response to DNA damage. This DNA repair phenotype can be fully rescued by over-expressing miR-24-insensitive H2AX. Therefore, miR-24 up-regulation in post-replicative cells reduces H2AX and thereby renders them highly vulnerable to DNA damage. PMID:19377482

  18. Correlation of initiating potency of skin carcinogens with potency to induce resistance to terminal differentiation in cultured mouse keratinocytes

    International Nuclear Information System (INIS)

    Kilkenny, A.E.; Morgan, D.; Spangler, E.F.; Yuspa, S.H.

    1985-01-01

    The induction by chemical carcinogens of resistance to terminal differentiation in cultured mouse keratinocytes has been proposed to represent a cellular change associated with the initiation phase of skin carcinogenesis. Previous results with this culture model indicated that the number of differentiation-resistant foci was correlated with the dose and known potency for several chemical carcinogens. Assay conditions were optimized to provide quantitative results for screening a variety of carcinogens for their potency as inducers of foci resistant to terminal differentiation. Eight skin initiators of varying potency and from different chemical classes and ultraviolet light were studied for their activity to induce this alteration in cultured epidermal cells from newborn BALB/c mice. There was an excellent positive correlation for the potency of these agents as initiators in vivo and as inducers of altered differentiation in vitro. The induction of resistant foci was independent of the relative cytotoxic effects of each agent except where cytotoxicity was extensive and reduced the number of foci. The results support the hypothesis that initiation of carcinogenesis in skin results in an alteration in the program of epidermal cell differentiation. The results also suggest that the assay is useful for identifying relative potency classes (strong, moderate, weak) of initiating agents

  19. Chromatin condensation in terminally differentiating mouse erythroblasts does not involve special architectural proteins but depends on histone deacetylation

    Energy Technology Data Exchange (ETDEWEB)

    Popova, Evgenya Y.; Krauss, Sharon Wald; Short, Sarah A.; Lee, Gloria; Villalobos, Jonathan; Etzell, Joan; Koury, Mark J.; Ney, Paul A.; Chasis, Joel Anne; Grigoryev, Sergei A.

    2008-08-21

    Terminal erythroid differentiation in vertebrates is characterized by progressive heterochromatin formation, chromatin condensation and, in mammals, culminates in nuclear extrusion. To date, although mechanisms regulating avian erythroid chromatin condensation have been identified, little is known regarding this process during mammalian erythropoiesis. To elucidate the molecular basis for mammalian erythroblast chromatin condensation, we used Friend virus-infected murine spleen erythroblasts that undergo terminal differentiation in vitro. Chromatin isolated from early and late stage erythroblasts had similar levels of linker and core histones, only a slight difference in nucleosome repeats, and no significant accumulation of known developmentally-regulated architectural chromatin proteins. However, histone H3(K9) dimethylation markedly increased while histone H4(K12) acetylation dramatically decreased and became segregated from the histone methylation as chromatin condensed. One histone deacetylase, HDAC5, was significantly upregulated during the terminal stages of Friend virus-infected erythroblast differentiation. Treatment with histone deacetylase inhibitor, trichostatin A, blocked both chromatin condensation and nuclear extrusion. Based on our data, we propose a model for a unique mechanism in which extensive histone deacetylation at pericentromeric heterochromatin mediates heterochromatin condensation in vertebrate erythroblasts that would otherwise be mediated by developmentally-regulated architectural proteins in nucleated blood cells.

  20. Enhanced electrochemical response in oxidative differential pulse voltammetry of dopamine in the presence of ascorbic acid at carboxyl-terminated boron-doped diamond electrodes

    International Nuclear Information System (INIS)

    Kondo, Takeshi; Niwano, Yu; Tamura, Akira; Imai, Junichi; Honda, Kensuke; Einaga, Yasuaki; Tryk, Donald A.; Fujishima, Akira; Kawai, Takeshi

    2009-01-01

    The differential pulse voltammetric (DPV) peak for dopamine (DA) oxidation was found to be highly amplified by the addition of ascorbic acid (AA) when carboxyl-terminated boron-doped diamond (BDD) electrodes were used as the working electrode. The DP voltammogram for a solution containing DA and AA obtained using a 4-pentenoic acid-modified BDD (4PA-BDD) electrode showed well-separated oxidation peaks for DA and AA at 0.4 and 0.6 V vs. Ag/AgCl, respectively. In addition, as the DA concentration increased at constant AA concentration, a simultaneous increase in the DA peak current density and decrease in the AA peak current density were observed. The slope of the calibration curve for the [DA] range of 1-10 μM in the presence of AA (500 μM) was seven times larger than that obtained in the absence of AA. Such an enhancement was found to be more efficient at 4PA-BDD than at oxidized-BDD, partly due to simple electrostatic effects and partly due to suppression of the polymerization of DA oxidation products by the terminal carboxyl groups. The enhanced detection method using a carboxyl-terminated BDD electrode should be an effective analytical tool, especially for determining low concentrations of DA in the presence of high concentrations of AA

  1. Enhanced electrochemical response in oxidative differential pulse voltammetry of dopamine in the presence of ascorbic acid at carboxyl-terminated boron-doped diamond electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Kondo, Takeshi [Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601 (Japan)], E-mail: t.kondo@ci.kagu.tus.ac.jp; Niwano, Yu; Tamura, Akira; Imai, Junichi [Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601 (Japan); Honda, Kensuke [Department of Chemistry and Earth Sciences, Faculty of Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi-shi, Yamaguchi 753-8521 (Japan); Einaga, Yasuaki [Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Yokohama 223-0012 (Japan); Tryk, Donald A. [Fuel Cell Nanomaterials Center, University of Yamanashi, Takeda 4-3-11, Kofu, Yamanashi 400-8511 (Japan); Fujishima, Akira [Kanagawa Academy of Science and Technology (KAST), 3-2-1 Sakado, Takatsu-ku, Kawasaki, Kanagawa 213-0012 (Japan); Kawai, Takeshi [Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601 (Japan)

    2009-03-01

    The differential pulse voltammetric (DPV) peak for dopamine (DA) oxidation was found to be highly amplified by the addition of ascorbic acid (AA) when carboxyl-terminated boron-doped diamond (BDD) electrodes were used as the working electrode. The DP voltammogram for a solution containing DA and AA obtained using a 4-pentenoic acid-modified BDD (4PA-BDD) electrode showed well-separated oxidation peaks for DA and AA at 0.4 and 0.6 V vs. Ag/AgCl, respectively. In addition, as the DA concentration increased at constant AA concentration, a simultaneous increase in the DA peak current density and decrease in the AA peak current density were observed. The slope of the calibration curve for the [DA] range of 1-10 {mu}M in the presence of AA (500 {mu}M) was seven times larger than that obtained in the absence of AA. Such an enhancement was found to be more efficient at 4PA-BDD than at oxidized-BDD, partly due to simple electrostatic effects and partly due to suppression of the polymerization of DA oxidation products by the terminal carboxyl groups. The enhanced detection method using a carboxyl-terminated BDD electrode should be an effective analytical tool, especially for determining low concentrations of DA in the presence of high concentrations of AA.

  2. Transcriptional profiling in response to terminal drought stress reveals differential responses along the wheat genome

    Directory of Open Access Journals (Sweden)

    Ferrari Francesco

    2009-06-01

    Full Text Available Abstract Background Water stress during grain filling has a marked effect on grain yield, leading to a reduced endosperm cell number and thus sink capacity to accumulate dry matter. The bread wheat cultivar Chinese Spring (CS, a Chinese Spring terminal deletion line (CS_5AL-10 and the durum wheat cultivar Creso were subjected to transcriptional profiling after exposure to mild and severe drought stress at the grain filling stage to find evidences of differential stress responses associated to different wheat genome regions. Results The transcriptome analysis of Creso, CS and its deletion line revealed 8,552 non redundant probe sets with different expression levels, mainly due to the comparisons between the two species. The drought treatments modified the expression of 3,056 probe sets. Besides a set of genes showing a similar drought response in Creso and CS, cluster analysis revealed several drought response features that can be associated to the different genomic structure of Creso, CS and CS_5AL-10. Some drought-related genes were expressed at lower level (or not expressed in Creso (which lacks the D genome or in the CS_5AL-10 deletion line compared to CS. The chromosome location of a set of these genes was confirmed by PCR-based mapping on the D genome (or the 5AL-10 region. Many clusters were characterized by different level of expression in Creso, CS and CS_AL-10, suggesting that the different genome organization of the three genotypes may affect plant adaptation to stress. Clusters with similar expression trend were grouped and functional classified to mine the biological mean of their activation or repression. Genes involved in ABA, proline, glycine-betaine and sorbitol pathways were found up-regulated by drought stress. Furthermore, the enhanced expression of a set of transposons and retrotransposons was detected in CS_5AL-10. Conclusion Bread and durum wheat genotypes were characterized by a different physiological reaction to water

  3. Glioblastoma Stem Cells Respond to Differentiation Cues but Fail to Undergo Commitment and Terminal Cell-Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Helena Carén

    2015-11-01

    Full Text Available Glioblastoma (GBM is an aggressive brain tumor whose growth is driven by stem cell-like cells. BMP signaling triggers cell-cycle exit and differentiation of GBM stem cells (GSCs and, therefore, might have therapeutic value. However, the epigenetic mechanisms that accompany differentiation remain poorly defined. It is also unclear whether cell-cycle arrest is terminal. Here we find only a subset of GSC cultures exhibit astrocyte differentiation in response to BMP. Although overtly differentiated non-cycling astrocytes are generated, they remain vulnerable to cell-cycle re-entry and fail to appropriately reconfigure DNA methylation patterns. Chromatin accessibility mapping identified loci that failed to alter in response to BMP and these were enriched in SOX transcription factor-binding motifs. SOX transcription factors, therefore, may limit differentiation commitment. A similar propensity for cell-cycle re-entry and de-differentiation was observed in GSC-derived oligodendrocyte-like cells. These findings highlight significant obstacles to BMP-induced differentiation as therapy for GBM.

  4. Sustained Low-Dose Treatment with the Histone Deacetylase Inhibitor LBH589 Induces Terminal Differentiation of Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Jason E. Cain

    2013-01-01

    Full Text Available Histone deacetylase inhibitors (HDACi were identified nearly four decades ago based on their ability to induce cellular differentiation. However, the clinical development of these compounds as cancer therapies has focused on their capacity to induce apoptosis in hematologic and lymphoid malignancies, often in combination with conventional cytotoxic agents. In many cases, HDACi doses necessary to induce these effects result in significant toxicity. Since osteosarcoma cells express markers of terminal osteoblast differentiation in response to DNA methyltransferase inhibitors, we reasoned that the epigenetic reprogramming capacity of HDACi might be exploited for therapeutic benefit. Here, we show that continuous exposure of osteosarcoma cells to low concentrations of HDACi LBH589 (Panobinostat over a three-week period induces terminal osteoblast differentiation and irreversible senescence without inducing cell death. Remarkably, transcriptional profiling revealed that HDACi therapy initiated gene signatures characteristic of chondrocyte and adipocyte lineages in addition to marked upregulation of mature osteoblast markers. In a mouse xenograft model, continuous low dose treatment with LBH589 induced a sustained cytostatic response accompanied by induction of mature osteoblast gene expression. These data suggest that the remarkable capacity of osteosarcoma cells to differentiate in response to HDACi therapy could be exploited for therapeutic benefit without inducing systemic toxicity.

  5. RNase L controls terminal adipocyte differentiation, lipids storage and insulin sensitivity via CHOP10 mRNA regulation

    DEFF Research Database (Denmark)

    Fabre, Odile Martine Julie; Salehzada, T; Lambert, K

    2012-01-01

    Adipose tissue structure is altered during obesity, leading to deregulation of whole-body metabolism. Its function depends on its structure, in particular adipocytes number and differentiation stage. To better understand the mechanisms regulating adipogenesis, we have investigated the role...... is associated with CHOP10 mRNA and regulates its stability. CHOP10 expression is conserved in RNase L(-/-)-MEFs, maintaining preadipocyte state while impairing their terminal differentiation. RNase L(-/-)-MEFs have decreased lipids storage capacity, insulin sensitivity and glucose uptake. Expression of ectopic...... RNase L in RNase L(-/-)-MEFs triggers CHOP10 mRNA instability, allowing increased lipids storage, insulin response and glucose uptake. Similarly, downregulation of CHOP10 mRNA with CHOP10 siRNA in RNase L(-/-)-MEFs improves their differentiation in adipocyte. In vivo, aged RNase L(-)/(-) mice present...

  6. Total and Differential Efficiencies for a Circular Detector Viewing a Circular Radiator of Finite Thickness

    Energy Technology Data Exchange (ETDEWEB)

    Lauber, A; Tollander, B

    1967-08-15

    Total and differential detection efficiencies have been computed for a circular detector viewing a circular radiator of finite thickness. Isotropic, cosines and n-p scattering angular emission distributions of the radiated particles are considered. Tables are given for the total efficiencies as well as for the differential efficiencies in the n-p scattering case.

  7. Differential subcellular localization of insulin receptor substrates depends on C-terminal regions and importin β

    International Nuclear Information System (INIS)

    Kabuta, Tomohiro; Take, Kazumi; Kabuta, Chihana; Hakuno, Fumihiko; Takahashi, Shin-Ichiro

    2008-01-01

    Insulin receptor substrates (IRSs) play essential roles in signal transduction of insulin and insulin-like growth factors. Previously, we showed that IRS-3 is localized to the nucleus as well as the cytosol, while IRS-1 and 2 are mainly localized to the cytoplasm. In the present study, we found that importin β directly interacts with IRS-3 and is able to mediate nuclear transport of IRS-3. Importin β interacted with the pleckstrin homology domain, the phosphotyrosine binding domain and the C-terminal region of IRS-3; indeed all of these fragments exhibited predominant nuclear localization. By contrast, almost no interaction of importin β with IRS-1 and -2 was observed, and their C-terminal regions displayed discrete spotty images in the cytosol. In addition, using chimeric proteins between IRS-1 and IRS-3, we revealed that the C-terminal regions are the main determinants of the differing subcellular localizations of IRS-1 and IRS-3.

  8. Terminal Differentiation of Adult Hippocampal Progenitor Cells Is a Step Functionally Dissociable from Proliferation and Is Controlled by Tis21, Id3 and NeuroD2

    OpenAIRE

    Laura Micheli; Manuela Ceccarelli; Roberta Gioia; Giorgio D’Andrea; Stefano Farioli-Vecchioli; Marco Costanzi; Daniele Saraulli; Daniele Saraulli; Vincenzo Cestari; Felice Tirone

    2017-01-01

    Cell proliferation and differentiation are interdependent processes. Here, we have asked to what extent the two processes of neural progenitor cell amplification and differentiation are functionally separated. Thus, we analyzed whether it is possible to rescue a defect of terminal differentiation in progenitor cells of the dentate gyrus, where new neurons are generated throughout life, by inducing their proliferation and/or their differentiation with different stimuli appropriately timed. As ...

  9. Interleukin-6 enhances human Ig production, but not as a terminal differentiation factor for B lymphocytes

    NARCIS (Netherlands)

    van Kooten, C.; van Oers, M. H.; Aarden, L. A.

    1990-01-01

    Most B-cell differentiation systems are complicated by the fact that they are both T-cell- and monocyte-dependent. Immobilized anti-CD3 antibodies induce monocyte-independent T-cell activation, allowing investigation of the role of interleukin-6 (IL6) in the process of B-cell differentiation. We

  10. Terminal Differentiation of Adult Hippocampal Progenitor Cells Is a Step Functionally Dissociable from Proliferation and Is Controlled by Tis21, Id3 and NeuroD2

    Directory of Open Access Journals (Sweden)

    Laura Micheli

    2017-07-01

    Full Text Available Cell proliferation and differentiation are interdependent processes. Here, we have asked to what extent the two processes of neural progenitor cell amplification and differentiation are functionally separated. Thus, we analyzed whether it is possible to rescue a defect of terminal differentiation in progenitor cells of the dentate gyrus, where new neurons are generated throughout life, by inducing their proliferation and/or their differentiation with different stimuli appropriately timed. As a model we used the Tis21 knockout mouse, whose dentate gyrus neurons, as demonstrated by us and others, have an intrinsic defect of terminal differentiation. We first tested the effect of two proliferative as well as differentiative neurogenic stimuli, one pharmacological (fluoxetine, the other cognitive (the Morris water maze (MWM training. Both effectively enhanced the number of new dentate gyrus neurons produced, and fluoxetine also reduced the S-phase length of Tis21 knockout dentate gyrus progenitor cells and increased the rate of differentiation of control cells, but neither factor enhanced the defective rate of differentiation. In contrast, the defect of terminal differentiation was fully rescued by in vivo infection of proliferating dentate gyrus progenitor cells with retroviruses either silencing Id3, an inhibitor of neural differentiation, or expressing NeuroD2, a proneural gene expressed in terminally differentiated dentate gyrus neurons. This is the first demonstration that NeuroD2 or the silencing of Id3 can activate the differentiation of dentate gyrus neurons, complementing a defect of differentiation. It also highlights how the rate of differentiation of dentate gyrus neurons is regulated genetically at several levels and that a neurogenic stimulus for amplification of neural stem/progenitor cells may not be sufficient in itself to modify this rate.

  11. Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination.

    Directory of Open Access Journals (Sweden)

    Samantha F Kornfeld

    Full Text Available Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as

  12. Computationally Efficient Transient Stability Modeling of multi-terminal VSC-HVDC

    DEFF Research Database (Denmark)

    van der Meer, Arjen A; Rueda-Torres, José; Silva, Filipe Miguel Faria da

    2016-01-01

    This paper studies the inclusion of averaged VSC-based grid interfaces and HVDC networks into stability type simulations, and compares the accuracy and speed of three multi-terminal DC dynamic models: 1) a state-space based model, 2) a multi-rate improved model, and 3) a reduced-order model...

  13. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA.

    Science.gov (United States)

    Warren, Luigi; Manos, Philip D; Ahfeldt, Tim; Loh, Yuin-Han; Li, Hu; Lau, Frank; Ebina, Wataru; Mandal, Pankaj K; Smith, Zachary D; Meissner, Alexander; Daley, George Q; Brack, Andrew S; Collins, James J; Cowan, Chad; Schlaeger, Thorsten M; Rossi, Derrick J

    2010-11-05

    Clinical application of induced pluripotent stem cells (iPSCs) is limited by the low efficiency of iPSC derivation and the fact that most protocols modify the genome to effect cellular reprogramming. Moreover, safe and effective means of directing the fate of patient-specific iPSCs toward clinically useful cell types are lacking. Here we describe a simple, nonintegrating strategy for reprogramming cell fate based on administration of synthetic mRNA modified to overcome innate antiviral responses. We show that this approach can reprogram multiple human cell types to pluripotency with efficiencies that greatly surpass established protocols. We further show that the same technology can be used to efficiently direct the differentiation of RNA-induced pluripotent stem cells (RiPSCs) into terminally differentiated myogenic cells. This technology represents a safe, efficient strategy for somatic cell reprogramming and directing cell fate that has broad applicability for basic research, disease modeling, and regenerative medicine. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Methyl CpG–binding proteins induce large-scale chromatin reorganization during terminal differentiation

    Science.gov (United States)

    Brero, Alessandro; Easwaran, Hariharan P.; Nowak, Danny; Grunewald, Ingrid; Cremer, Thomas; Leonhardt, Heinrich; Cardoso, M. Cristina

    2005-01-01

    Pericentric heterochromatin plays an important role in epigenetic gene regulation. We show that pericentric heterochromatin aggregates during myogenic differentiation. This clustering leads to the formation of large chromocenters and correlates with increased levels of the methyl CpG–binding protein MeCP2 and pericentric DNA methylation. Ectopic expression of fluorescently tagged MeCP2 mimicked this effect, causing a dose-dependent clustering of chromocenters in the absence of differentiation. MeCP2-induced rearrangement of heterochromatin occurred throughout interphase, did not depend on the H3K9 histone methylation pathway, and required the methyl CpG–binding domain (MBD) only. Similar to MeCP2, another methyl CpG–binding protein, MBD2, also increased during myogenic differentiation and could induce clustering of pericentric regions, arguing for functional redundancy. This MeCP2- and MBD2-mediated chromatin reorganization may thus represent a molecular link between nuclear genome topology and the epigenetic maintenance of cellular differentiation. PMID:15939760

  15. Efficient Numerical Methods for Stochastic Differential Equations in Computational Finance

    KAUST Repository

    Happola, Juho

    2017-09-19

    Stochastic Differential Equations (SDE) offer a rich framework to model the probabilistic evolution of the state of a system. Numerical approximation methods are typically needed in evaluating relevant Quantities of Interest arising from such models. In this dissertation, we present novel effective methods for evaluating Quantities of Interest relevant to computational finance when the state of the system is described by an SDE.

  16. Efficient Numerical Methods for Stochastic Differential Equations in Computational Finance

    KAUST Repository

    Happola, Juho

    2017-01-01

    Stochastic Differential Equations (SDE) offer a rich framework to model the probabilistic evolution of the state of a system. Numerical approximation methods are typically needed in evaluating relevant Quantities of Interest arising from such models. In this dissertation, we present novel effective methods for evaluating Quantities of Interest relevant to computational finance when the state of the system is described by an SDE.

  17. Development of a Medical Care Terminal for Efficient Monitoring of Bedridden Subjects

    OpenAIRE

    Pereira, Filipe; Carvalho, Vítor; Soares, Filomena; Machado, José; Bezerra, Karolina; Silva, Rui; Matos, Demétrio

    2016-01-01

    This work is developed in the context of Ambient Assisted Living (AAL) and has as main objective the development of a mechatronic system that allows the care of bedridden patients with ongoing medical care handled by a single person. The developed Medical Care Terminal (MCT) improves autonomy in home care, safety, comfort, and hygiene of bedridden patients. The MCT has six biomedical sensors and four environmental sensors. Data acquisition and processing is performed using Arduino and Lab VIE...

  18. A Plastid Terminal Oxidase Associated with Carotenoid Desaturation during Chromoplast Differentiation1

    Science.gov (United States)

    Josse, Eve-Marie; Simkin, Andrew J.; Gaffé, Joël; Labouré, Anne-Marie; Kuntz, Marcel; Carol, Pierre

    2000-01-01

    The Arabidopsis IMMUTANS gene encodes a plastid homolog of the mitochondrial alternative oxidase, which is associated with phytoene desaturation. Upon expression in Escherichia coli, this protein confers a detectable cyanide-resistant electron transport to isolated membranes. In this assay this activity is sensitive to n-propyl-gallate, an inhibitor of the alternative oxidase. This protein appears to be a plastid terminal oxidase (PTOX) that is functionally equivalent to a quinol:oxygen oxidoreductase. This protein was immunodetected in achlorophyllous pepper (Capsicum annuum) chromoplast membranes, and a corresponding cDNA was cloned from pepper and tomato (Lycopersicum esculentum) fruits. Genomic analysis suggests the presence of a single gene in these organisms, the expression of which parallels phytoene desaturase and ζ-carotene desaturase gene expression during fruit ripening. Furthermore, this PTOX gene is impaired in the tomato ghost mutant, which accumulates phytoene in leaves and fruits. These data show that PTOX also participates in carotenoid desaturation in chromoplasts in addition to its role during early chloroplast development. PMID:10938359

  19. Balancing electrical and optical losses for efficient Si-perovskite 4-terminal solar cells with solution processed percolation electrodes.

    KAUST Repository

    Ramírez Quiroz, César Omar

    2018-01-15

    The unprecedented efficiency upraise of perovskite-based photovoltaics has sparked the interest in semi-transparent devices, particularly for tandem structures. Despite promising reports regarding efficiency and reduced parasitic absorption, many devices still rely on processes from the gas phase, compromising both applicability and cost factors. Here, we report all-solution perovskite solar cells with improved infrared transparency ideally suited as top-cell for efficient multi-junction device configurations. We demonstrate the functionality of Copper (I) thiocyanate as antireflective layer and selective contact between the transparent conductive oxide and the perovskite as key factor. This concept allows us to fabricate an opaque device with steady state efficiency as high as 20.1%. By employing silver nanowires with robust environmental stability as bottom electrode, we demonstrate different regimes of device performance that can be described through a classical percolation model, leading to semi-transparent solar cells with efficiencies of up to 17.1%. In conjunction with the implementation of an infrared-tuned transparent conductive oxide contact deposited on UV-fused silica, we show a full device average transmittance surpassing 84% between 800 and 1100 nm (as opposed to 77% with PEDOT:PSS as selective contact). Finally, we mechanically staked optimized perovskite devices on top of high performing PERL and IBC silicon architectures. The imputed output efficiency of the 4-terminal measured perovskite-silicon solar cell was 26.7% and 25.2% for PERL-perovskite and IBC-perovskite, respectively.

  20. Balancing electrical and optical losses for efficient Si-perovskite 4-terminal solar cells with solution processed percolation electrodes.

    KAUST Repository

    Ramí rez Quiroz, Cé sar Omar; Shen, Yilei; Salvador, Michael; Forberich, Karen; Schrenker, Nadine; Spyropulos, George D.; Huemueller, Thomas; Wilkinson, Benjamin; Kirchartz, Thomas; Spiecker, Erdmann; Verlinden, Pierre J.; Zhang, Xueling; Green, Martin; Ho-Baillie, Anita Wing Yi; Brabec, Christoph J

    2018-01-01

    The unprecedented efficiency upraise of perovskite-based photovoltaics has sparked the interest in semi-transparent devices, particularly for tandem structures. Despite promising reports regarding efficiency and reduced parasitic absorption, many devices still rely on processes from the gas phase, compromising both applicability and cost factors. Here, we report all-solution perovskite solar cells with improved infrared transparency ideally suited as top-cell for efficient multi-junction device configurations. We demonstrate the functionality of Copper (I) thiocyanate as antireflective layer and selective contact between the transparent conductive oxide and the perovskite as key factor. This concept allows us to fabricate an opaque device with steady state efficiency as high as 20.1%. By employing silver nanowires with robust environmental stability as bottom electrode, we demonstrate different regimes of device performance that can be described through a classical percolation model, leading to semi-transparent solar cells with efficiencies of up to 17.1%. In conjunction with the implementation of an infrared-tuned transparent conductive oxide contact deposited on UV-fused silica, we show a full device average transmittance surpassing 84% between 800 and 1100 nm (as opposed to 77% with PEDOT:PSS as selective contact). Finally, we mechanically staked optimized perovskite devices on top of high performing PERL and IBC silicon architectures. The imputed output efficiency of the 4-terminal measured perovskite-silicon solar cell was 26.7% and 25.2% for PERL-perovskite and IBC-perovskite, respectively.

  1. Highly efficient differentiation of embryonic stem cells into adipocytes by ascorbic acid

    OpenAIRE

    Ixchelt Cuaranta-Monroy; Zoltan Simandi; Zsuzsanna Kolostyak; Quang-Minh Doan-Xuan; Szilard Poliska; Attila Horvath; Gergely Nagy; Zsolt Bacso; Laszlo Nagy

    2014-01-01

    Adipocyte differentiation and function have become the major research targets due to the increasing interest in obesity and related metabolic conditions. Although, late stages of adipogenesis have been extensively studied, the early phases remain poorly understood. Here we present that supplementing ascorbic acid (AsA) to the adipogenic differentiation cocktail enables the robust and efficient differentiation of mouse embryonic stem cells (mESCs) to mature adipocytes. Such ESC-derived adipocy...

  2. Regulation of Silk Genes by Hox and Homeodomain Proteins in the Terminal Differentiated Silk Gland of the Silkworm Bombyx mori

    Science.gov (United States)

    Takiya, Shigeharu; Tsubota, Takuya; Kimoto, Mai

    2016-01-01

    The silk gland of the silkworm Bombyx mori is a long tubular organ that is divided into several subparts along its anteroposterior (AP) axis. As a trait of terminal differentiation of the silk gland, several silk protein genes are expressed with unique regional specificities. Most of the Hox and some of the homeobox genes are also expressed in the differentiated silk gland with regional specificities. The expression patterns of Hox genes in the silk gland roughly correspond to those in embryogenesis showing “colinearity”. The central Hox class protein Antennapedia (Antp) directly regulates the expression of several middle silk gland–specific silk genes, whereas the Lin-1/Isl-1/Mec3 (LIM)-homeodomain transcriptional factor Arrowhead (Awh) regulates the expression of posterior silk gland–specific genes for silk fiber proteins. We summarize our results and discuss the usefulness of the silk gland of Bombyx mori for analyzing the function of Hox genes. Further analyses of the regulatory mechanisms underlying the region-specific expression of silk genes will provide novel insights into the molecular bases for target-gene selection and regulation by Hox and homeodomain proteins. PMID:29615585

  3. Regulation of Silk Genes by Hox and Homeodomain Proteins in the Terminal Differentiated Silk Gland of the Silkworm Bombyx mori

    Directory of Open Access Journals (Sweden)

    Shigeharu Takiya

    2016-05-01

    Full Text Available The silk gland of the silkworm Bombyx mori is a long tubular organ that is divided into several subparts along its anteroposterior (AP axis. As a trait of terminal differentiation of the silk gland, several silk protein genes are expressed with unique regional specificities. Most of the Hox and some of the homeobox genes are also expressed in the differentiated silk gland with regional specificities. The expression patterns of Hox genes in the silk gland roughly correspond to those in embryogenesis showing “colinearity”. The central Hox class protein Antennapedia (Antp directly regulates the expression of several middle silk gland–specific silk genes, whereas the Lin-1/Isl-1/Mec3 (LIM-homeodomain transcriptional factor Arrowhead (Awh regulates the expression of posterior silk gland–specific genes for silk fiber proteins. We summarize our results and discuss the usefulness of the silk gland of Bombyx mori for analyzing the function of Hox genes. Further analyses of the regulatory mechanisms underlying the region-specific expression of silk genes will provide novel insights into the molecular bases for target-gene selection and regulation by Hox and homeodomain proteins.

  4. Computationally efficient statistical differential equation modeling using homogenization

    Science.gov (United States)

    Hooten, Mevin B.; Garlick, Martha J.; Powell, James A.

    2013-01-01

    Statistical models using partial differential equations (PDEs) to describe dynamically evolving natural systems are appearing in the scientific literature with some regularity in recent years. Often such studies seek to characterize the dynamics of temporal or spatio-temporal phenomena such as invasive species, consumer-resource interactions, community evolution, and resource selection. Specifically, in the spatial setting, data are often available at varying spatial and temporal scales. Additionally, the necessary numerical integration of a PDE may be computationally infeasible over the spatial support of interest. We present an approach to impose computationally advantageous changes of support in statistical implementations of PDE models and demonstrate its utility through simulation using a form of PDE known as “ecological diffusion.” We also apply a statistical ecological diffusion model to a data set involving the spread of mountain pine beetle (Dendroctonus ponderosae) in Idaho, USA.

  5. Efficient sortase-mediated N-terminal labeling of TEV protease cleaved recombinant proteins.

    Science.gov (United States)

    Sarpong, Kwabena; Bose, Ron

    2017-03-15

    A major challenge in attaching fluorophores or other handles to proteins is the availability of a site-specific labeling strategy that provides stoichiometric modification without compromising protein integrity. We developed a simple approach that combines TEV protease cleavage, sortase modification and affinity purification to N-terminally label proteins. To achieve stoichiometrically-labeled protein, we included a short affinity tag in the fluorophore-containing peptide for post-labeling purification of the modified protein. This strategy can be easily applied to any recombinant protein with a TEV site and we demonstrate this on Epidermal Growth Factor Receptor (EGFR) and Membrane Scaffold Protein (MSP) constructs. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Efficient switching of 3-terminal magnetic tunnel junctions by the giant spin Hall effect of Pt85Hf15 alloy

    Science.gov (United States)

    Nguyen, Minh-Hai; Shi, Shengjie; Rowlands, Graham E.; Aradhya, Sriharsha V.; Jermain, Colin L.; Ralph, D. C.; Buhrman, R. A.

    2018-02-01

    Recent research has indicated that introducing impurities that increase the resistivity of Pt can enhance the efficiency of the spin Hall torque it generates. Here, we directly demonstrate the usefulness of this strategy by fabricating prototype 3-terminal in-plane-magnetized magnetic tunnel junctions that utilize the spin Hall torque from a Pt85Hf15 alloy and measuring the critical currents for switching. We find that Pt85Hf15 reduces the switching current densities compared to pure Pt by approximately a factor of 2 for both quasi-static ramped current biases and nanosecond-scale current pulses, thereby proving the feasibility of this approach in assisting the development of efficient embedded magnetic memory technologies.

  7. N-Terminal Pro-B-Type Natriuretic Peptide and Phonocardiography in Differentiating Innocent Cardiac Murmurs from Congenital Cardiac Anomalies in Asymptomatic Puppies

    NARCIS (Netherlands)

    Marinus, S M; Engelen, H.G.H.; Szatmári, V.

    2017-01-01

    Background: Differentiating innocent cardiac murmurs from murmurs caused by congenital cardiac anomalies can be challenging with auscultation alone in asymptomatic puppies. Hypothesis: Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations and phonocardiograms recorded by an

  8. Analysis of differential lipofection efficiency in primary and established myoblasts.

    Science.gov (United States)

    Pampinella, Francesca; Lechardeur, Delphine; Zanetti, Elena; MacLachlan, Ian; Benharouga, Mohammed; Lukacs, Gergely L; Vitiello, Libero

    2002-02-01

    In this study we have compared the process of lipid-mediated transfection in primary and established myoblasts, in an attempt to elucidate the mechanisms responsible for the scarce transfectability of the former. We determined the metabolic stability of cytoplasmically injected and lipofected DNA in primary and established myoblasts and carried out a comparative time course analysis of luciferase reporter-gene expression and DNA stability. The efficiency of the transcription-translation machinery of the two cell types was compared by intranuclear injection of naked plasmid DNA encoding luciferase. Subcellular colocalization of fluorescein-labeled lipopolyplexes with specific endosomal and lysosomal markers was performed by confocal microscopy to monitor the intracellular trafficking of plasmid DNA during transfection. The metabolic stability of plasmid DNA was similar in primary and established myoblasts after both lipofection and cytoplasmic injection. In both cell types, lipofection had no detectable effect on the rate of cell proliferation. Confocal analysis showed that nuclear translocation of transfected DNA coincided with localization in a compartment devoid of endosome- or lysosome-specific marker proteins. The residency time of plasmid DNA in this compartment differed for primary and established myoblasts. Our findings suggest that the lower transfectability of primary myoblasts is mostly due to a difference in the intracellular delivery pathway that correlates with more rapid delivery of internalized complex to the lysosomal compartment.

  9. Measuring the external quantum efficiency of two-terminal polymer tandem solar cells

    NARCIS (Netherlands)

    Gilot, J.; Wienk, M.M.; Janssen, R.A.J.

    2010-01-01

    Tandem configurations, in which two cells are stacked and connected in series, offer a viable approach to further increase the power conversion efficiency (PCE) of organic solar cells. To enable the future rational design of new materials it is important to accurately assess the contributions of

  10. [Influence of different lighting levels at workstations with video display terminals on operators' work efficiency].

    Science.gov (United States)

    Janosik, Elzbieta; Grzesik, Jan

    2003-01-01

    The aim of this work was to evaluate the influence of different lighting levels at workstations with video display terminals (VDTs) on the course of the operators' visual work, and to determine the optimal levels of lighting at VDT workstations. For two kinds of job (entry of figures from a typescript and edition of the text displayed on the screen), the work capacity, the degree of the visual strain and the operators' subjective symptoms were determined for four lighting levels (200, 300, 500 and 750 lx). It was found that the work at VDT workstations may overload the visual system and cause eyes complaints as well as the reduction of accommodation or convergence strength. It was also noted that the edition of the text displayed on the screen is more burdening for operators than the entry of figures from a typescript. Moreover, the examination results showed that the lighting at VDT workstations should be higher than 200 lx and that 300 lx makes the work conditions most comfortable during the entry of figures from a typescript, and 500 lx during the edition of the text displayed on the screen.

  11. Development of a Medical Care Terminal for Efficient Monitoring of Bedridden Subjects

    Directory of Open Access Journals (Sweden)

    Filipe Pereira

    2016-01-01

    Full Text Available This work is developed in the context of Ambient Assisted Living (AAL and has as main objective the development of a mechatronic system that allows the care of bedridden patients with ongoing medical care handled by a single person. The developed Medical Care Terminal (MCT improves autonomy in home care, safety, comfort, and hygiene of bedridden patients. The MCT has six biomedical sensors and four environmental sensors. Data acquisition and processing is performed using Arduino and LabVIEW platforms, respectively. The proposed solution has, as main feature, its adaptability to the patient needs. One of the MCT functionalities is the remote access to the patient data through the web. The caregiver may request help from a specialist who sends back information in real time to perform first aid assistance. This device has a flexible configuration allowing a fast and cheap reconfiguration according the specific needs of the patient. The proposed mechatronic system intends to meet the needs of bedridden patients improving their quality of life, health, safety, and comfort, while enabling the remote monitoring of the patients.

  12. Functionalization with C-terminal cysteine enhances transfection efficiency of cell-penetrating peptides through dimer formation

    Energy Technology Data Exchange (ETDEWEB)

    Amand, Helene L., E-mail: helene.amand@chalmers.se [Chalmers University of Technology, Department of Chemical and Biological Engineering/Physical Chemistry, SE-412 96 Gothenburg (Sweden); Norden, Bengt, E-mail: norden@chalmers.se [Chalmers University of Technology, Department of Chemical and Biological Engineering/Physical Chemistry, SE-412 96 Gothenburg (Sweden); Fant, Kristina, E-mail: kristina.fant@sp.se [Chalmers University of Technology, Department of Chemical and Biological Engineering/Physical Chemistry, SE-412 96 Gothenburg (Sweden)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer Reversible CPP dimerisation is a simple yet efficient strategy to improve delivery. Black-Right-Pointing-Pointer Dimer formation enhances peptiplex stability, resulting in increased transfection. Black-Right-Pointing-Pointer By dimerisation, the CPP EB1 even gain endosomal escape properties while lowering cytotoxicity. -- Abstract: Cell-penetrating peptides have the ability to stimulate uptake of macromolecular cargo in mammalian cells in a non-toxic manner and therefore hold promise as efficient and well tolerated gene delivery vectors. Non-covalent peptide-DNA complexes ('peptiplexes') enter cells via endocytosis, but poor peptiplex stability and endosomal entrapment are considered as main barriers to peptide-mediated delivery. We explore a simple, yet highly efficient, strategy to improve the function of peptide-based vectors, by adding one terminal cysteine residue. This allows the peptide to dimerize by disulfide bond formation, increasing its affinity for nucleic acids by the 'chelate effect' and, when the bond is reduced intracellularly, letting the complex dissociate to deliver the nucleic acid. By introducing a single C-terminal cysteine in the classical CPP penetratin and the penetratin analogs PenArg and EB1, we show that this minor modification greatly enhances the transfection capacity for plasmid DNA in HEK293T cells. We conclude that this effect is mainly due to enhanced thermodynamic stability of the peptiplexes as endosome-disruptive chloroquine is still required for transfection and the effect is more pronounced for peptides with lower inherent DNA condensation capacity. Interestingly, for EB1, addition of one cysteine makes the peptide able to mediate transfection in absence of chloroquine, indicating that dimerisation can also improve endosomal escape properties. Further, the cytotoxicity of EB1 peptiplexes is considerably reduced, possibly due to lower concentration of free peptide

  13. Efficient Semitransparent Perovskite Solar Cells Using a Transparent Silver Electrode and Four-Terminal Perovskite/Silicon Tandem Device Exploration

    Directory of Open Access Journals (Sweden)

    Dazheng Chen

    2018-01-01

    Full Text Available Four-terminal tandem solar cells employing a perovskite top cell and crystalline silicon (Si bottom cell offer a simpler pathway to surpass the efficiency limit of market-leading single-junction silicon solar cells. To obtain cost-effective top cells, it is crucial to develop transparent conductive electrodes with low parasitic absorption and manufacturing cost. The commonly used indium tin oxide (ITO shows some drawbacks, like the increasing prices and high-energy magnetron sputtering process. Transparent metal electrodes are promising candidates owing to the simple evaporation process, facile process conditions, and high conductivity, and the cheaper silver (Ag electrode with lower parasitic absorption than gold may be the better choice. In this work, efficient semitransparent perovskite solar cells (PSCs were firstly developed by adopting the composite cathode of an ultrathin Ag electrode at its percolation threshold thickness (11 nm, a molybdenum oxide optical coupling layer, and a bathocuproine interfacial layer. The resulting power conversion efficiency (PCE is 13.38% when the PSC is illuminated from the ITO side and the PCE is 8.34% from the Ag side, and no obvious current hysteresis can be observed. Furthermore, by stacking an industrial Si bottom cell (PCE = 14.2% to build a four-terminal architecture, the overall PCEs of 17.03% (ITO side and 11.60% (Ag side can be obtained, which are 27% and 39% higher, respectively, than those of the perovskite top cell. Also, the PCE of the tandem cell has exceeded that of the reference Si solar cell by about 20%. This work provides an outlook to fabricate high-performance solar cells via the cost-effective pathway.

  14. Functionalization with C-terminal cysteine enhances transfection efficiency of cell-penetrating peptides through dimer formation

    International Nuclear Information System (INIS)

    Åmand, Helene L.; Nordén, Bengt; Fant, Kristina

    2012-01-01

    Highlights: ► Reversible CPP dimerisation is a simple yet efficient strategy to improve delivery. ► Dimer formation enhances peptiplex stability, resulting in increased transfection. ► By dimerisation, the CPP EB1 even gain endosomal escape properties while lowering cytotoxicity. -- Abstract: Cell-penetrating peptides have the ability to stimulate uptake of macromolecular cargo in mammalian cells in a non-toxic manner and therefore hold promise as efficient and well tolerated gene delivery vectors. Non-covalent peptide-DNA complexes (“peptiplexes”) enter cells via endocytosis, but poor peptiplex stability and endosomal entrapment are considered as main barriers to peptide-mediated delivery. We explore a simple, yet highly efficient, strategy to improve the function of peptide-based vectors, by adding one terminal cysteine residue. This allows the peptide to dimerize by disulfide bond formation, increasing its affinity for nucleic acids by the “chelate effect” and, when the bond is reduced intracellularly, letting the complex dissociate to deliver the nucleic acid. By introducing a single C-terminal cysteine in the classical CPP penetratin and the penetratin analogs PenArg and EB1, we show that this minor modification greatly enhances the transfection capacity for plasmid DNA in HEK293T cells. We conclude that this effect is mainly due to enhanced thermodynamic stability of the peptiplexes as endosome-disruptive chloroquine is still required for transfection and the effect is more pronounced for peptides with lower inherent DNA condensation capacity. Interestingly, for EB1, addition of one cysteine makes the peptide able to mediate transfection in absence of chloroquine, indicating that dimerisation can also improve endosomal escape properties. Further, the cytotoxicity of EB1 peptiplexes is considerably reduced, possibly due to lower concentration of free peptide dimer resulting from its stronger binding to DNA.

  15. Fbxw7-associated drug resistance is reversed by induction of terminal differentiation in murine intestinal organoid culture

    Directory of Open Access Journals (Sweden)

    Federica Lorenzi

    2016-01-01

    Full Text Available Colorectal cancer (CRC is one of the top three cancer-related causes of death worldwide. FBXW7 is a known tumor-suppressor gene, commonly mutated in CRC and in a variety of other epithelial tumors. Low expression of FBXW7 is also associated with poor prognosis. Loss of FBXW7 sensitizes cancer cells to certain drugs, while making them more resistant to other types of chemotherapies. However, is not fully understood how epithelial cells within normal gut and primary tumors respond to potential cancer therapeutics. We have studied genetically engineered mice in which the fbxw7 gene is conditionally knocked-out in the intestine (fbxw7ΔG. To further investigate the mechanism of Fbxw7-action, we grew intestinal crypts from floxed-fbxw7 (fbxw7fl/fl and fbxw7ΔG mice, in a Matrigel-based organoid (mini-gut culture. The fbxw7ΔG organoids exhibited rapid budding events in the crypt region. Furthermore, to test organoids for drug response, we exposed day 3 intestinal organoids from fbxw7fl/fl and fbxw7ΔG mice, to various concentrations of 5-fluorouracil (5-FU for 72 hours. 5-FU triggers phenotypic differences in organoids including changing shape, survival, resistance, and death. 5-FU however, rescues the drug-resistance phenotype of fbxw7ΔG through the induction of terminal differentiation. Our results support the hypothesis that a differentiating therapy successfully targets FBXW7-mutated CRC cells.

  16. Abrupt onset of mutations in a developmentally regulated gene during terminal differentiation of post-mitotic photoreceptor neurons in mice.

    Directory of Open Access Journals (Sweden)

    Ivette M Sandoval

    Full Text Available For sensitive detection of rare gene repair events in terminally differentiated photoreceptors, we generated a knockin mouse model by replacing one mouse rhodopsin allele with a form of the human rhodopsin gene that causes a severe, early-onset form of retinitis pigmentosa. The human gene contains a premature stop codon at position 344 (Q344X, cDNA encoding the enhanced green fluorescent protein (EGFP at its 3' end, and a modified 5' untranslated region to reduce translation rate so that the mutant protein does not induce retinal degeneration. Mutations that eliminate the stop codon express a human rhodopsin-EGFP fusion protein (hRho-GFP, which can be readily detected by fluorescence microscopy. Spontaneous mutations were observed at a frequency of about one per retina; in every case, they gave rise to single fluorescent rod cells, indicating that each mutation occurred during or after the last mitotic division. Additionally, the number of fluorescent rods did not increase with age, suggesting that the rhodopsin gene in mature rod cells is less sensitive to mutation than it is in developing rods. Thus, there is a brief developmental window, coinciding with the transcriptional activation of the rhodopsin locus, in which somatic mutations of the rhodopsin gene abruptly begin to appear.

  17. Epidermal cell-shape regulation and subpopulation kinetics during butyrate-induced terminal maturation of normal and SV40-transformed human keratinocytes: epithelial models of differentiation therapy.

    Science.gov (United States)

    Staiano-Coico, L; Steinberg, M; Higgins, P J

    1990-10-15

    Recent data indicate that malignant human epidermal cells may be appropriate targets for sodium butyrate (NaB)-mediated differentiation therapy. The response of pre- and post-crisis populations of SV40-transformed human keratinocytes (SVKs) to this differentiation-inducing agent was assessed, therefore, within the framework of NaB-directed normal human keratinocyte (NHK) maturation. NaB augmented cornified envelope (CE) production in NHK and pre-crisis SVK cultures; the time-course and efficiency of induced maturation were similar in the 2 cell systems. In NHKs, the percentage of amplifying ("B" substate) cells decreased with time in NaB correlating with increases in both "C" stage keratinocytes and CEs. The latter formed over one or 2 layers of nucleated basal-like cells. Inductions were accompanied by immediate cell cycle blocks (in both the G1 and G2/M phases), reorganization within the actin cytoskeleton, and transient early increases in cellular actin content. Increased NHK and pre-crisis SVK cytoskeletal-associated actin reached a maximum approximately 48 hr after NaB addition and preceded development of CEs. The CE precursors, thus, probably reside in the "B" substate. Post-crisis SVKs, in contrast, were refractive to NaB-induced terminal maturation or cell-cycle perturbation, failed to initiate actin filament rearrangements, and retained a basal cell-like phenotype. Stable transformation of human SVKs in post-crisis phase, therefore, appears to be associated with loss of maturation "competence" within the "B" keratinocyte subpopulation.

  18. Myeloblastic leukemia cells conditionally blocked by myc-estrogen receptor chimeric transgenes for terminal differentiation coupled to growth arrest and apoptosis.

    Science.gov (United States)

    Selvakumaran, M; Liebermann, D; Hoffman-Liebermann, B

    1993-05-01

    Conditional mutants of the myeloblastic leukemic M1 cell line, expressing the chimeric mycer transgene, have been established. It is shown that M1 mycer cells, like M1, undergo terminal differentiation coupled to growth arrest and programmed cell death (apoptosis) after treatment with the physiologic differentiation inducer interleukin-6. However, when beta-estradiol is included in the culture medium, M1 mycer cells respond to differentiation inducers like M1 myc cell lines, where the differentiation program is blocked at an intermediate stage. By manipulating the function of the mycer transgene product, it is shown that there is a 10-hour window during myeloid differentiation, from 30 to 40 hours after the addition of the differentiation inducer, when the terminal differentiation program switches from being dependent on c-myc suppression to becoming c-myc suppression independent, where activation of c-myc has no apparent effect on mature macrophages. M1 mycer cell lines provide a powerful tool to increase our understanding of the role of c-myc in normal myelopoiesis and in leukemogenesis, also providing a strategy to clone c-myc target genes.

  19. Replisome speed determines the efficiency of the Tus−Ter replication termination barrier

    KAUST Repository

    Elshenawy, Mohamed; Jergic, Slobodan; Xu, Zhi Qiang; Sobhy, Mohamed Abdelmaboud; Takahashi, Masateru; Oakley, Aaron J.; Dixon, Nicholas E.; Hamdan, Samir

    2015-01-01

    In all domains of life, DNA synthesis occurs bidirectionally from replication origins. Despite variable rates of replication fork progression, fork convergence often occurs at specific sites. Escherichia coli sets a 'replication fork trap' that allows the first arriving fork to enter but not to leave the terminus region. The trap is set by oppositely oriented Tus-bound Ter sites that block forks on approach from only one direction. However, the efficiency of fork blockage by Tus-Ter does not exceed 50% in vivo despite its apparent ability to almost permanently arrest replication forks in vitro. Here we use data from single-molecule DNA replication assays and structural studies to show that both polarity and fork-arrest efficiency are determined by a competition between rates of Tus displacement and rearrangement of Tus-Ter interactions that leads to blockage of slower moving replisomes by two distinct mechanisms. To our knowledge this is the first example where intrinsic differences in rates of individual replisomes have different biological outcomes. ©2015 Macmillan Publishers Limited. All rights reserved.

  20. Replisome speed determines the efficiency of the Tus−Ter replication termination barrier

    KAUST Repository

    Elshenawy, Mohamed

    2015-08-31

    In all domains of life, DNA synthesis occurs bidirectionally from replication origins. Despite variable rates of replication fork progression, fork convergence often occurs at specific sites. Escherichia coli sets a \\'replication fork trap\\' that allows the first arriving fork to enter but not to leave the terminus region. The trap is set by oppositely oriented Tus-bound Ter sites that block forks on approach from only one direction. However, the efficiency of fork blockage by Tus-Ter does not exceed 50% in vivo despite its apparent ability to almost permanently arrest replication forks in vitro. Here we use data from single-molecule DNA replication assays and structural studies to show that both polarity and fork-arrest efficiency are determined by a competition between rates of Tus displacement and rearrangement of Tus-Ter interactions that leads to blockage of slower moving replisomes by two distinct mechanisms. To our knowledge this is the first example where intrinsic differences in rates of individual replisomes have different biological outcomes. ©2015 Macmillan Publishers Limited. All rights reserved.

  1. Synthesis of novel vitamin K derivatives with alkylated phenyl groups introduced at the ω-terminal side chain and evaluation of their neural differentiation activities.

    Science.gov (United States)

    Sakane, Rie; Kimura, Kimito; Hirota, Yoshihisa; Ishizawa, Michiyasu; Takagi, Yuta; Wada, Akimori; Kuwahara, Shigefumi; Makishima, Makoto; Suhara, Yoshitomo

    2017-11-01

    Vitamin K is an essential cofactor of γ-glutamylcarboxylase as related to blood coagulation and bone formation. Menaquinone-4, one of the vitamin K homologues, is biosynthesized in the body and has various biological activities such as being a ligand for steroid and xenobiotic receptors, protection of neuronal cells from oxidative stress, and so on. From this background, we focused on the role of menaquinone in the differentiation activity of progenitor cells into neuronal cells and we synthesized novel vitamin K derivatives with modification of the ω-terminal side chain. We report here new vitamin K analogues, which introduced an alkylated phenyl group at the ω-terminal side chain. These compounds exhibited potent differentiation activity as compared to control. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  2. Serum-free Erythroid Differentiation for Efficient Genetic Modification and High-Level Adult Hemoglobin Production.

    Science.gov (United States)

    Uchida, Naoya; Demirci, Selami; Haro-Mora, Juan J; Fujita, Atsushi; Raines, Lydia N; Hsieh, Matthew M; Tisdale, John F

    2018-06-15

    In vitro erythroid differentiation from primary human cells is valuable to develop genetic strategies for hemoglobin disorders. However, current erythroid differentiation methods are encumbered by modest transduction rates and high baseline fetal hemoglobin production. In this study, we sought to improve both genetic modification and hemoglobin production among human erythroid cells in vitro . To model therapeutic strategies, we transduced human CD34 + cells and peripheral blood mononuclear cells (PBMCs) with lentiviral vectors and compared erythropoietin-based erythroid differentiation using fetal-bovine-serum-containing media and serum-free media. We observed more efficient transduction (85%-93%) in serum-free media than serum-containing media (20%-69%), whereas the addition of knockout serum replacement (KSR) was required for serum-free media to promote efficient erythroid differentiation (96%). High-level adult hemoglobin production detectable by electrophoresis was achieved using serum-free media similar to serum-containing media. Importantly, low fetal hemoglobin production was observed in the optimized serum-free media. Using KSR-containing, serum-free erythroid differentiation media, therapeutic adult hemoglobin production was detected at protein levels with β-globin lentiviral transduction in both CD34 + cells and PBMCs from sickle cell disease subjects. Our in vitro erythroid differentiation system provides a practical evaluation platform for adult hemoglobin production among human erythroid cells following genetic manipulation.

  3. IL-27 Receptor Signalling Restricts the Formation of Pathogenic, Terminally Differentiated Th1 Cells during Malaria Infection by Repressing IL-12 Dependent Signals

    Science.gov (United States)

    Villegas-Mendez, Ana; de Souza, J. Brian; Lavelle, Seen-Wai; Gwyer Findlay, Emily; Shaw, Tovah N.; van Rooijen, Nico; Saris, Christiaan J.; Hunter, Christopher A.; Riley, Eleanor M.; Couper, Kevin N.

    2013-01-01

    The IL-27R, WSX-1, is required to limit IFN-γ production by effector CD4+ T cells in a number of different inflammatory conditions but the molecular basis of WSX-1-mediated regulation of Th1 responses in vivo during infection has not been investigated in detail. In this study we demonstrate that WSX-1 signalling suppresses the development of pathogenic, terminally differentiated (KLRG-1+) Th1 cells during malaria infection and establishes a restrictive threshold to constrain the emergent Th1 response. Importantly, we show that WSX-1 regulates cell-intrinsic responsiveness to IL-12 and IL-2, but the fate of the effector CD4+ T cell pool during malaria infection is controlled primarily through IL-12 dependent signals. Finally, we show that WSX-1 regulates Th1 cell terminal differentiation during malaria infection through IL-10 and Foxp3 independent mechanisms; the kinetics and magnitude of the Th1 response, and the degree of Th1 cell terminal differentiation, were comparable in WT, IL-10R1−/− and IL-10−/− mice and the numbers and phenotype of Foxp3+ cells were largely unaltered in WSX-1−/− mice during infection. As expected, depletion of Foxp3+ cells did not enhance Th1 cell polarisation or terminal differentiation during malaria infection. Our results significantly expand our understanding of how IL-27 regulates Th1 responses in vivo during inflammatory conditions and establishes WSX-1 as a critical and non-redundant regulator of the emergent Th1 effector response during malaria infection. PMID:23593003

  4. Differential isotope dansylation labeling combined with liquid chromatography mass spectrometry for quantification of intact and N-terminal truncated proteins

    International Nuclear Information System (INIS)

    Tang, Yanan; Li, Liang

    2013-01-01

    Graphical abstract: -- Highlights: •LC–MS was developed for quantifying protein mixtures containing both intact and N-terminal truncated proteins. • 12 C 2 -Dansylation of the N-terminal amino acid of proteins was done first, followed by microwave-assisted acid hydrolysis. •The released 12 C 2 -dansyl labeled N-terminal amino acid was quantified using 13 C 2 -dansyl labeled amino acid standards. •The method provided accurate and precise results for quantifying intact and N-terminal truncated proteins within 8 h. -- Abstract: The N-terminal amino acids of proteins are important structure units for maintaining the biological function, localization, and interaction networks of proteins. Under different biological conditions, one or several N-terminal amino acids could be cleaved from an intact protein due to processes, such as proteolysis, resulting in the change of protein properties. Thus, the ability to quantify the N-terminal truncated forms of proteins is of great importance, particularly in the area of development and production of protein-based drugs where the relative quantity of the intact protein and its truncated form needs to be monitored. In this work, we describe a rapid method for absolute quantification of protein mixtures containing intact and N-terminal truncated proteins. This method is based on dansylation labeling of the N-terminal amino acids of proteins, followed by microwave-assisted acid hydrolysis of the proteins into amino acids. It is shown that dansyl labeled amino acids are stable in acidic conditions and can be quantified by liquid chromatography mass spectrometry (LC–MS) with the use of isotope analog standards

  5. Differential isotope dansylation labeling combined with liquid chromatography mass spectrometry for quantification of intact and N-terminal truncated proteins

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yanan; Li, Liang, E-mail: Liang.Li@ualberta.ca

    2013-08-20

    Graphical abstract: -- Highlights: •LC–MS was developed for quantifying protein mixtures containing both intact and N-terminal truncated proteins. •{sup 12}C{sub 2}-Dansylation of the N-terminal amino acid of proteins was done first, followed by microwave-assisted acid hydrolysis. •The released {sup 12}C{sub 2}-dansyl labeled N-terminal amino acid was quantified using {sup 13}C{sub 2}-dansyl labeled amino acid standards. •The method provided accurate and precise results for quantifying intact and N-terminal truncated proteins within 8 h. -- Abstract: The N-terminal amino acids of proteins are important structure units for maintaining the biological function, localization, and interaction networks of proteins. Under different biological conditions, one or several N-terminal amino acids could be cleaved from an intact protein due to processes, such as proteolysis, resulting in the change of protein properties. Thus, the ability to quantify the N-terminal truncated forms of proteins is of great importance, particularly in the area of development and production of protein-based drugs where the relative quantity of the intact protein and its truncated form needs to be monitored. In this work, we describe a rapid method for absolute quantification of protein mixtures containing intact and N-terminal truncated proteins. This method is based on dansylation labeling of the N-terminal amino acids of proteins, followed by microwave-assisted acid hydrolysis of the proteins into amino acids. It is shown that dansyl labeled amino acids are stable in acidic conditions and can be quantified by liquid chromatography mass spectrometry (LC–MS) with the use of isotope analog standards.

  6. Embryoid body attachment to reconstituted basement membrane induces a genetic program of epithelial differentiation via jun N-terminal kinase signaling.

    Science.gov (United States)

    Ho, Hoang-Yen; Moffat, Ryan C; Patel, Rupal V; Awah, Franklin N; Baloue, Kaitrin; Crowe, David L

    2010-09-01

    Embryonic stem (ES) cells are derived from early stage mammalian embryos and have broad developmental potential. These cells can be manipulated experimentally to generate cells of multiple tissue types which could be important in treating human diseases. The ability to produce relevant amounts of these differentiated cell populations creates the basis for clinical interventions in tissue regeneration and repair. Understanding how embryonic stem cells differentiate also can reveal important insights into cell biology. A previously reported mouse embryonic stem cell model demonstrated that differentiated epithelial cells migrated out of embryoid bodies attached to reconstituted basement membrane. We used genomic technology to profile ES cell populations in order to understand the molecular mechanisms leading to epithelial differentiation. Cells with characteristics of cultured epithelium migrated from embryoid bodies attached to reconstituted basement membrane. However, cells that comprised embryoid bodies also rapidly lost ES cell-specific gene expression and expressed proteins characteristic of stratified epithelia within hours of attachment to basement membrane. Gene expression profiling of sorted cell populations revealed upregulation of the BMP/TGFbeta signaling pathway, which was not sufficient for epithelial differentiation in the absence of basement membrane attachment. Activation of c-jun N-terminal kinase 1 (JNK1) and increased expression of Jun family transcription factors was observed during epithelial differentiation of ES cells. Inhibition of JNK signaling completely blocked epithelial differentiation in this model, revealing a key mechanism by which ES cells adopt epithelial characteristics via basement membrane attachment. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  7. Synthetic Glycopolymers for Highly Efficient Differentiation of Embryonic Stem Cells into Neurons: Lipo- or Not?

    Science.gov (United States)

    Liu, Qi; Lyu, Zhonglin; Yu, You; Zhao, Zhen-Ao; Hu, Shijun; Yuan, Lin; Chen, Gaojian; Chen, Hong

    2017-04-05

    To realize the potential application of embryonic stem cells (ESCs) for the treatment of neurodegenerative diseases, it is a prerequisite to develop an effective strategy for the neural differentiation of ESCs so as to obtain adequate amount of neurons. Considering the efficacy of glycosaminoglycans (GAG) and their disadvantages (e.g., structure heterogeneity and impurity), GAG-mimicking glycopolymers (designed polymers containing functional units similar to natural GAG) with or without phospholipid groups were synthesized in the present work and their ability to promote neural differentiation of mouse ESCs (mESCs) was investigated. It was found that the lipid-anchored GAG-mimicking glycopolymers (lipo-pSGF) retained on the membrane of mESCs rather than being internalized by cells after 1 h of incubation. Besides, lipo-pSGF showed better activity in promoting neural differentiation. The expression of the neural-specific maker β3-tubulin in lipo-pSGF-treated cells was ∼3.8- and ∼1.9-fold higher compared to natural heparin- and pSGF-treated cells at day 14. The likely mechanism involved in lipo-pSGF-mediated neural differentiation was further investigated by analyzing its effect on fibroblast growth factor 2 (FGF2)-mediated extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway which is important for neural differentiation of ESCs. Lipo-pSGF was found to efficiently bind FGF2 and enhance the phosphorylation of ERK1/2, thus promoting neural differentiation. These findings demonstrated that engineering of cell surface glycan using our synthetic lipo-glycopolymer is a highly efficient approach for neural differentiation of ESCs and this strategy can be applied for the regulation of other cellular activities mediated by cell membrane receptors.

  8. An N-terminal peptide extension results in efficient expression, but not secretion, of a synthetic horseradish peroxidase gene in transgenic tobacco.

    Science.gov (United States)

    Kis, Mihaly; Burbridge, Emma; Brock, Ian W; Heggie, Laura; Dix, Philip J; Kavanagh, Tony A

    2004-03-01

    Native horseradish (Armoracia rusticana) peroxidase, HRP (EC 1.11.1.7), isoenzyme C is synthesized with N-terminal and C-terminal peptide extensions, believed to be associated with protein targeting. This study aimed to explore the specific functions of these extensions, and to generate transgenic plants with expression patterns suitable for exploring the role of peroxidase in plant development and defence. Transgenic Nicotiana tabacum (tobacco) plants expressing different versions of a synthetic horseradish peroxidase, HRP, isoenzyme C gene were constructed. The gene was engineered to include additional sequences coding for either the natural N-terminal or the C-terminal extension or both. These constructs were placed under the control of a constitutive promoter (CaMV-35S) or the tobacco RUBISCO-SSU light inducible promoter (SSU) and introduced into tobacco using Agrobacterium-mediated transformation. To study the effects of the N- and C-terminal extensions, the localization of recombinant peroxidase was determined using biochemical and molecular techniques. Transgenic tobacco plants can exhibit a ten-fold increase in peroxidase activity compared with wild-type tobacco levels, and the majority of this activity is located in the symplast. The N-terminal extension is essential for the production of high levels of recombinant protein, while the C-terminal extension has little effect. Differences in levels of enzyme activity and recombinant protein are reflected in transcript levels. There is no evidence to support either preferential secretion or vacuolar targeting of recombinant peroxidase in this heterologous expression system. This leads us to question the postulated targeting roles of these peptide extensions. The N-terminal extension is essential for high level expression and appears to influence transcript stability or translational efficiency. Plants have been generated with greatly elevated cytosolic peroxidase activity, and smaller increases in apoplastic

  9. Visualization of living terminal hypertrophic chondrocytes of growth plate cartilage in situ by differential interference contrast microscopy and time-lapse cinematography.

    Science.gov (United States)

    Farnum, C E; Turgai, J; Wilsman, N J

    1990-09-01

    The functional unit within the growth plate consists of a column of chondrocytes that passes through a sequence of phases including proliferation, hypertrophy, and death. It is important to our understanding of the biology of the growth plate to determine if distal hypertrophic cells are viable, highly differentiated cells with the potential of actively controlling terminal events of endochondral ossification prior to their death at the chondro-osseous junction. This study for the first time reports on the visualization of living hypertrophic chondrocytes in situ, including the terminal hypertrophic chondrocyte. Chondrocytes in growth plate explants are visualized using rectified differential interference contrast microscopy. We record and measure, using time-lapse cinematography, the rate of movement of subcellular organelles at the limit of resolution of this light microscopy system. Control experiments to assess viability of hypertrophic chondrocytes include coincubating organ cultures with the intravital dye fluorescein diacetate to assess the integrity of the plasma membrane and cytoplasmic esterases. In this system, all hypertrophic chondrocytes, including the very terminal chondrocyte, exist as rounded, fully hydrated cells. By the criteria of intravital dye staining and organelle movement, distal hypertrophic chondrocytes are identical to chondrocytes in the proliferative and early hypertrophic cell zones.

  10. Regulator of differentiation 1 (ROD1) binds to the amphipathic C-terminal peptide of thrombospondin-4 and is involved in its mitogenic activity.

    Science.gov (United States)

    Sadvakassova, Gulzhakhan; Dobocan, Monica C; Difalco, Marcos R; Congote, Luis F

    2009-09-01

    The matrix protein thrombospondin-4 has an acidic amphipathic C-terminal peptide (C21) which stimulates erythroid cell proliferation. Here we show that C21 stimulates red cell formation in anemic mice in vivo. In vitro experiments indicated that the peptide-mediated increase of erythroid colony formation in cultures of human CD34+ hematopoietic progenitor cells was possible only under continuous presence of erythropoietin. In the absence of this cytokine, C21 stimulated exclusively myeloid colony formation. Therefore, the peptide is not a specific erythroid differentiation factor. In fact, it is mitogenic in non-erythroid cells, such as skin fibroblasts and kidney epithelial cells. In erythroleukemic TF-1 cells, it actually decreased the production of the erythroid differentiation marker glycophorin A. C21-affinity chromatography revealed regulator of differentiation 1 (ROD1) as a major C21-binding protein. ROD1 is the hematopoietic cell paralog of polypyrimidine tract binding proteins (PTBs), RNA splice regulators which regulate differentiation by repressing tissue-specific exons. ROD1 binding to C21 was strongly inhibited by synthetic RNAs in the order poly A > poly U > poly G = poly C and was weakly inhibited by a synthetic phosphorylated peptide mimicking the C-terminal domain of RNA polymerase II. Cellular overexpression or knockdown experiments of ROD1 suggest a role for this protein in the mitogenic activity of C21. Since the nuclear proteins ROD1 and PTBs regulate differentiation at a posttranscriptional level and there is a fast nuclear uptake of C21, we put forward the idea that the peptide is internalized, goes to the nucleus and maintains cells in a proliferative state by supporting ROD1-mediated inhibition of differentiation.

  11. Efficient solution of ordinary differential equations modeling electrical activity in cardiac cells.

    Science.gov (United States)

    Sundnes, J; Lines, G T; Tveito, A

    2001-08-01

    The contraction of the heart is preceded and caused by a cellular electro-chemical reaction, causing an electrical field to be generated. Performing realistic computer simulations of this process involves solving a set of partial differential equations, as well as a large number of ordinary differential equations (ODEs) characterizing the reactive behavior of the cardiac tissue. Experiments have shown that the solution of the ODEs contribute significantly to the total work of a simulation, and there is thus a strong need to utilize efficient solution methods for this part of the problem. This paper presents how an efficient implicit Runge-Kutta method may be adapted to solve a complicated cardiac cell model consisting of 31 ODEs, and how this solver may be coupled to a set of PDE solvers to provide complete simulations of the electrical activity.

  12. Differential functions of C- and N-terminal hepatitis B x protein in liver cells treated with doxorubicin in normoxic or hypoxic condition.

    Directory of Open Access Journals (Sweden)

    Davor Kin-Fan Chau

    Full Text Available Hepatitis viral B x protein (HBx, a hepatocarcinogen, is frequently mutated. Hypoxia influences the growth of HCC and also the sensitivity of tumor cells to treatments. We aimed to test the role of HBx and acute hypoxia in the efficacy of chemotherapy. In this study, we established 4 Chang liver cell lines with the full-length HBx (HBx, the first 50 amino acids of N-terminal HBx (HBx/50, the last 104 amino acids of C-terminal HBx (HBx/51 and empty vector (CL, respectively. MTT and TNUEL assays were used to assess cell viability and apoptosis respectively. Western blot was used to determine the expression of relevant proteins. Results showed that among 4 cell lines, doxorubicin was most effective in decreasing the viability and enhancing apoptosis in HBx/51 cells, while HBx/50 cells were most resistant to the treatment. Cells in hypoxia were more susceptible to doxorubicin than cells in normoxia. Hypoxia facilitated the Bid cleavage especially in HBx/51 cells via phosphorylating p38 MAPK. p38 MAPK inhibitor significantly reduced the tBid level and increased cell viability. In conclusion, N-terminal HBx and C-terminal HBx function differentially in their ability to regulate cell growth, with the former being promotive but the latter being inhibitory. The acute hypoxia may overcome the HBx-induced resistance and facilitate the chemotherapy.

  13. Differentiation, international equity and efficiency in the fight against the global climatic change

    International Nuclear Information System (INIS)

    Blanchard, O.; Criqui, P.; Viguier, L.; Trommetter, M.

    1998-05-01

    The first difficulty to get over in the international negotiation on the climatic change, has been and still remain the distribution of the efforts and the research of the equity in the objective determination. This paper analyzes the possible consequences of the negotiable emission licenses in terms of efficiency and equity. The first part is a review of the different charts of the objectives differentiation discussed or proposed in the international negotiation process on the greenhouse effect. It aims to find a bond between the the charts and the equity. The second part deals with the programs cost and their relative efficiency, taking into account the marginal cost curves. (A.L.B.)

  14. Investigating market efficiency through a forecasting model based on differential equations

    Science.gov (United States)

    de Resende, Charlene C.; Pereira, Adriano C. M.; Cardoso, Rodrigo T. N.; de Magalhães, A. R. Bosco

    2017-05-01

    A new differential equation based model for stock price trend forecast is proposed as a tool to investigate efficiency in an emerging market. Its predictive power showed statistically to be higher than the one of a completely random model, signaling towards the presence of arbitrage opportunities. Conditions for accuracy to be enhanced are investigated, and application of the model as part of a trading strategy is discussed.

  15. High efficient differentiation of functional hepatocytes from porcine induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Ying Ao

    Full Text Available Hepatocyte transplantation is considered to be a promising therapy for patients with liver diseases. Induced pluripotent stem cells (iPSCs provide an unlimited source for the generation of functional hepatocytes. In this study, we generated iPSCs from porcine ear fibroblasts (PEFs by overexpressing Sox2, Klf4, Oct4, and c-Myc (SKOM, and developed a novel strategy for the efficient differentiation of hepatocyte-like cells from porcine iPSCs by following the processes of early liver development. The differentiated cells displayed the phenotypes of hepatocytes, exhibited classic hepatocyte-associated bio-functions, such as LDL uptake, glycogen storage and urea secretion, as well as possessed the metabolic activities of cytochrome P-450 (CYP 3A and 2C. Furthermore, we compared the hepatocyte differentiation efficacy of our protocol with another published method, and the results demonstrated that our differentiation strategy could significantly improve the generation of morphological and functional hepatocyte-like cells from porcine iPSCs. In conclusion, this study establishes an efficient method for in vitro generation of functional hepatocytes from porcine iPSCs, which could represent a promising cell source for preclinical testing of cell-based therapeutics for liver failure and for pharmacological applications.

  16. Increased numbers of preexisting memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells.

    Science.gov (United States)

    Joshi, Nikhil S; Cui, Weiguo; Dominguez, Claudia X; Chen, Jonathan H; Hand, Timothy W; Kaech, Susan M

    2011-10-15

    Memory CD8 T cells acquire effector memory cell properties after reinfection and may reach terminally differentiated, senescent states ("Hayflick limit") after multiple infections. The signals controlling this process are not well understood, but we found that the degree of secondary effector and memory CD8 T cell differentiation was intimately linked to the amount of T-bet expressed upon reactivation and preexisting memory CD8 T cell number (i.e., primary memory CD8 T cell precursor frequency) present during secondary infection. Compared with naive cells, memory CD8 T cells were predisposed toward terminal effector (TE) cell differentiation because they could immediately respond to IL-12 and induce T-bet, even in the absence of Ag. TE cell formation after secondary (2°) or tertiary infections was dependent on increased T-bet expression because T-bet(+/-) cells were resistant to these phenotypic changes. Larger numbers of preexisting memory CD8 T cells limited the duration of 2° infection and the amount of IL-12 produced, and consequently, this reduced T-bet expression and the proportion of 2° TE CD8 T cells that formed. Together, these data show that over repeated infections, memory CD8 T cell quality and proliferative fitness is not strictly determined by the number of serial encounters with Ag or cell divisions, but is a function of the CD8 T cell differentiation state, which is genetically controlled in a T-bet-dependent manner. This differentiation state can be modulated by preexisting memory CD8 T cell number and the intensity of inflammation during reinfection. These results have important implications for vaccinations involving prime-boost strategies.

  17. Extended passaging increases the efficiency of neural differentiation from induced pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Koehler Karl R

    2011-08-01

    Full Text Available Abstract Background The use of induced pluripotent stem cells (iPSCs for the functional replacement of damaged neurons and in vitro disease modeling is of great clinical relevance. Unfortunately, the capacity of iPSC lines to differentiate into neurons is highly variable, prompting the need for a reliable means of assessing the differentiation capacity of newly derived iPSC cell lines. Extended passaging is emerging as a method of ensuring faithful reprogramming. We adapted an established and efficient embryonic stem cell (ESC neural induction protocol to test whether iPSCs (1 have the competence to give rise to functional neurons with similar efficiency as ESCs and (2 whether the extent of neural differentiation could be altered or enhanced by increased passaging. Results Our gene expression and morphological analyses revealed that neural conversion was temporally delayed in iPSC lines and some iPSC lines did not properly form embryoid bodies during the first stage of differentiation. Notably, these deficits were corrected by continual passaging in an iPSC clone. iPSCs with greater than 20 passages (late-passage iPSCs expressed higher expression levels of pluripotency markers and formed larger embryoid bodies than iPSCs with fewer than 10 passages (early-passage iPSCs. Moreover, late-passage iPSCs started to express neural marker genes sooner than early-passage iPSCs after the initiation of neural induction. Furthermore, late-passage iPSC-derived neurons exhibited notably greater excitability and larger voltage-gated currents than early-passage iPSC-derived neurons, although these cells were morphologically indistinguishable. Conclusions These findings strongly suggest that the efficiency neuronal conversion depends on the complete reprogramming of iPSCs via extensive passaging.

  18. Cell population structure prior to bifurcation predicts efficiency of directed differentiation in human induced pluripotent cells.

    Science.gov (United States)

    Bargaje, Rhishikesh; Trachana, Kalliopi; Shelton, Martin N; McGinnis, Christopher S; Zhou, Joseph X; Chadick, Cora; Cook, Savannah; Cavanaugh, Christopher; Huang, Sui; Hood, Leroy

    2017-02-28

    Steering the differentiation of induced pluripotent stem cells (iPSCs) toward specific cell types is crucial for patient-specific disease modeling and drug testing. This effort requires the capacity to predict and control when and how multipotent progenitor cells commit to the desired cell fate. Cell fate commitment represents a critical state transition or "tipping point" at which complex systems undergo a sudden qualitative shift. To characterize such transitions during iPSC to cardiomyocyte differentiation, we analyzed the gene expression patterns of 96 developmental genes at single-cell resolution. We identified a bifurcation event early in the trajectory when a primitive streak-like cell population segregated into the mesodermal and endodermal lineages. Before this branching point, we could detect the signature of an imminent critical transition: increase in cell heterogeneity and coordination of gene expression. Correlation analysis of gene expression profiles at the tipping point indicates transcription factors that drive the state transition toward each alternative cell fate and their relationships with specific phenotypic readouts. The latter helps us to facilitate small molecule screening for differentiation efficiency. To this end, we set up an analysis of cell population structure at the tipping point after systematic variation of the protocol to bias the differentiation toward mesodermal or endodermal cell lineage. We were able to predict the proportion of cardiomyocytes many days before cells manifest the differentiated phenotype. The analysis of cell populations undergoing a critical state transition thus affords a tool to forecast cell fate outcomes and can be used to optimize differentiation protocols to obtain desired cell populations.

  19. An Efficient Numerical Approach for Solving Nonlinear Coupled Hyperbolic Partial Differential Equations with Nonlocal Conditions

    Directory of Open Access Journals (Sweden)

    A. H. Bhrawy

    2014-01-01

    Full Text Available One of the most important advantages of collocation method is the possibility of dealing with nonlinear partial differential equations (PDEs as well as PDEs with variable coefficients. A numerical solution based on a Jacobi collocation method is extended to solve nonlinear coupled hyperbolic PDEs with variable coefficients subject to initial-boundary nonlocal conservation conditions. This approach, based on Jacobi polynomials and Gauss-Lobatto quadrature integration, reduces solving the nonlinear coupled hyperbolic PDEs with variable coefficients to a system of nonlinear ordinary differential equation which is far easier to solve. In fact, we deal with initial-boundary coupled hyperbolic PDEs with variable coefficients as well as initial-nonlocal conditions. Using triangular, soliton, and exponential-triangular solutions as exact solutions, the obtained results show that the proposed numerical algorithm is efficient and very accurate.

  20. Efficient detection of differentially methylated regions using DiMmeR

    DEFF Research Database (Denmark)

    Almeida, Diogo Marinho; Uhrenfeldt Skov, Ida; Silva, Artur

    2017-01-01

    in the programming language R, have no user interface, and do not offer all necessary steps to guide users from raw data all the way down to statistically significant differentially methylated regions (DMRs) and the associated genes. RESULTS: Here, we present DiMmeR (Discovery of Multiple Differentially Methylated...... Regions), the first free standalone software that interactively guides with a user-friendly graphical user interface (GUI) scientists the whole way through EWAS data analysis. It offers parallelized statistical methods for efficiently identifying DMRs in both Illumina 450K and 850K EPIC chip data. Di......MmeR computes empirical p-values through randomization tests, even for big data sets of hundreds of patients and thousands of permutations within a few minutes on a standard desktop PC. It is independent of any third-party libraries, computes regression coefficients, p-values and empirical p...

  1. Water Use Efficiency and Water Deficit Tolerance Indices in Terminal Growth Stages in Promising Bread Wheat genotypes

    Directory of Open Access Journals (Sweden)

    M. Nazeri

    2016-02-01

    Full Text Available Introduction During growth stages of wheat, anthesis and grain filling periods are the most susceptible to drought. Wheat cultivars that are more tolerant to terminal drought are more suitable to Mediterranean conditions. To increase water use efficiency, the target environment should be taken into account, because one trait might be effective in an environment but ineffective in another environment. In general, some traits like early vigour and root absorbtion capacity are so important in water deficient conditions. In recent years, increasing grain yield was due to increasing grain numbers. Although both the source and sink is considered as the limitation factors in increasing grain yield in old cultivars, even in the new cultivars sink seems to be more important. In fact, phenological adjustment adapted with seasonal precipitation pattern can improve water use efficiency in drought conditions. Suitable flowering time is the most important trait that is correlated with increasing water use efficiency in drought conditions. Materials and Methods In order to evaluate the level of drought tolerance in promising bread wheat lines, a split plot arrangements using randomized complete block design with three replications was carried out in 2008-09 and 2009-10 growing seasons at Torogh Agricultural Research Field Station, Mashhad. in. water limited conditions at three levels Optimum moisture conditions (L1, removal irrigation and using rain shelter from milky grain stage to maturity (L2, removal irrigation and using rainshelter from anthesis to maturity (L3 were assigned to main plots. Ten bread wheat lines include suitable for cold and dry regions (V1: (Toos, V2: (C-81-10, V3: (pishgam, V4: (C-84-4, V5: (C-84-8, V6: (C-D-85-15, V7: (C-D-85-9, V8: (C-D-84-5502, V9: (C-D-85-5502 and V10: (C-85-6 were randomized in sub-plots. Stress susceptibility index (SSI, stress tolerance index (STI and tolerance (TOL were calculated using following equations: D = 1

  2. Differential gene expression of wheat progeny with contrasting levels of transpiration efficiency.

    Science.gov (United States)

    Xue, Gang-Ping; McIntyre, C Lynne; Chapman, Scott; Bower, Neil I; Way, Heather; Reverter, Antonio; Clarke, Bryan; Shorter, Ray

    2006-08-01

    High water use efficiency or transpiration efficiency (TE) in wheat is a desirable physiological trait for increasing grain yield under water-limited environments. The identification of genes associated with this trait would facilitate the selection for genotypes with higher TE using molecular markers. We performed an expression profiling (microarray) analysis of approximately 16,000 unique wheat ESTs to identify genes that were differentially expressed between wheat progeny lines with contrasting TE levels from a cross between Quarrion (high TE) and Genaro 81 (low TE). We also conducted a second microarray analysis to identify genes responsive to drought stress in wheat leaves. Ninety-three genes that were differentially expressed between high and low TE progeny lines were identified. One fifth of these genes were markedly responsive to drought stress. Several potential growth-related regulatory genes, which were down-regulated by drought, were expressed at a higher level in the high TE lines than the low TE lines and are potentially associated with a biomass production component of the Quarrion-derived high TE trait. Eighteen of the TE differentially expressed genes were further analysed using quantitative RT-PCR on a separate set of plant samples from those used for microarray analysis. The expression levels of 11 of the 18 genes were positively correlated with the high TE trait, measured as carbon isotope discrimination (Delta(13)C). These data indicate that some of these TE differentially expressed genes are candidates for investigating processes that underlie the high TE trait or for use as expression quantitative trait loci (eQTLs) for TE.

  3. Efficient Numerical Solution of Coupled Radial Differential Equations in Multichannel Scattering Problems

    International Nuclear Information System (INIS)

    Houfek, Karel

    2008-01-01

    Numerical solution of coupled radial differential equations which are encountered in multichannel scattering problems is presented. Numerical approach is based on the combination of the exterior complex scaling method and the finite-elements method with the discrete variable representation. This method can be used not only to solve multichannel scattering problem but also to find bound states and resonance positions and widths directly by diagonalization of the corresponding complex scaled Hamiltonian. Efficiency and accuracy of this method is demonstrated on an analytically solvable two-channel problem.

  4. Efficient Galerkin solution of stochastic fractional differential equations using second kind Chebyshev wavelets

    Directory of Open Access Journals (Sweden)

    Fakhrodin Mohammadi

    2017-10-01

    Full Text Available ‎Stochastic fractional differential equations (SFDEs have been used for modeling many physical problems in the fields of turbulance‎, ‎heterogeneous‎, ‎flows and matrials‎, ‎viscoelasticity and electromagnetic theory‎. ‎In this paper‎, ‎an‎ efficient wavelet Galerkin method based on the second kind Chebyshev wavelets are proposed for approximate solution of SFDEs‎. ‎In ‎this ‎app‎roach‎‎, ‎o‎perational matrices of the second kind Chebyshev wavelets ‎are used ‎for reducing SFDEs to a linear system of algebraic equations that can be solved easily‎. ‎C‎onvergence and error analysis of the proposed method is ‎considered‎.‎ ‎Some numerical examples are performed to confirm the applicability and efficiency of the proposed method‎.

  5. On Improving Efficiency of Differential Evolution for Aerodynamic Shape Optimization Applications

    Science.gov (United States)

    Madavan, Nateri K.

    2004-01-01

    Differential Evolution (DE) is a simple and robust evolutionary strategy that has been proven effective in determining the global optimum for several difficult optimization problems. Although DE offers several advantages over traditional optimization approaches, its use in applications such as aerodynamic shape optimization where the objective function evaluations are computationally expensive is limited by the large number of function evaluations often required. In this paper various approaches for improving the efficiency of DE are reviewed and discussed. These approaches are implemented in a DE-based aerodynamic shape optimization method that uses a Navier-Stokes solver for the objective function evaluations. Parallelization techniques on distributed computers are used to reduce turnaround times. Results are presented for the inverse design of a turbine airfoil. The efficiency improvements achieved by the different approaches are evaluated and compared.

  6. Cobalt(III)-catalyzed alkenylation of arenes and 6-arylpurines with terminal alkynes: efficient access to functional dyes.

    Science.gov (United States)

    Wang, Shan; Hou, Ji-Ting; Feng, Mei-Lin; Zhang, Xiao-Zhuan; Chen, Shan-Yong; Yu, Xiao-Qi

    2016-02-14

    Alkenylation of unactivated arenes and 6-arylpurines with terminal alkynes in high yields using Cp*Co(CO)I2 as catalyst under mild conditions is described. This method shows outstanding functional group compatibility and can be applied in the design of a mitochondria-targeted imaging dye.

  7. An N‐terminal Peptide Extension Results in Efficient Expression, but not Secretion, of a Synthetic Horseradish Peroxidase Gene in Transgenic Tobacco

    Science.gov (United States)

    KIS, MIHALY; BURBRIDGE, EMMA; BROCK, IAN W.; HEGGIE, LAURA; DIX, PHILIP J.; KAVANAGH, TONY A.

    2004-01-01

    • Background and Aims Native horseradish (Armoracia rusticana) peroxidase, HRP (EC 1.11.1.7), isoenzyme C is synthesized with N‐terminal and C‐terminal peptide extensions, believed to be associated with protein targeting. This study aimed to explore the specific functions of these extensions, and to generate transgenic plants with expression patterns suitable for exploring the role of peroxidase in plant development and defence. • Methods Transgenic Nicotiana tabacum (tobacco) plants expressing different versions of a synthetic horseradish peroxidase, HRP, isoenzyme C gene were constructed. The gene was engineered to include additional sequences coding for either the natural N‐terminal or the C‐terminal extension or both. These constructs were placed under the control of a constitutive promoter (CaMV‐35S) or the tobacco RUBISCO‐SSU light inducible promoter (SSU) and introduced into tobacco using Agrobacterium‐mediated transformation. To study the effects of the N‐ and C‐terminal extensions, the localization of recombinant peroxidase was determined using biochemical and molecular techniques. • Key Results Transgenic tobacco plants can exhibit a ten‐fold increase in peroxidase activity compared with wild‐type tobacco levels, and the majority of this activity is located in the symplast. The N‐terminal extension is essential for the production of high levels of recombinant protein, while the C‐terminal extension has little effect. Differences in levels of enzyme activity and recombinant protein are reflected in transcript levels. • Conclusions There is no evidence to support either preferential secretion or vacuolar targeting of recombinant peroxidase in this heterologous expression system. This leads us to question the postulated targeting roles of these peptide extensions. The N‐terminal extension is essential for high level expression and appears to influence transcript stability or translational efficiency. Plants have been

  8. Value-based differential pricing: efficient prices for drugs in a global context.

    Science.gov (United States)

    Danzon, Patricia; Towse, Adrian; Mestre-Ferrandiz, Jorge

    2015-03-01

    This paper analyzes pharmaceutical pricing between and within countries to achieve second-best static and dynamic efficiency. We distinguish countries with and without universal insurance, because insurance undermines patients' price sensitivity, potentially leading to prices above second-best efficient levels. In countries with universal insurance, if each payer unilaterally sets an incremental cost-effectiveness ratio (ICER) threshold based on its citizens' willingness-to-pay for health; manufacturers price to that ICER threshold; and payers limit reimbursement to patients for whom a drug is cost-effective at that price and ICER, then the resulting price levels and use within each country and price differentials across countries are roughly consistent with second-best static and dynamic efficiency. These value-based prices are expected to differ cross-nationally with per capita income and be broadly consistent with Ramsey optimal prices. Countries without comprehensive insurance avoid its distorting effects on prices but also lack financial protection and affordability for the poor. Improving pricing efficiency in these self-pay countries includes improving regulation and consumer information about product quality and enabling firms to price discriminate within and between countries. © 2013 The Authors. Health Economics published by John Wiley & Sons Ltd.

  9. TGF-β receptors, in a Smad-independent manner, are required for terminal skeletal muscle differentiation

    International Nuclear Information System (INIS)

    Droguett, Rebeca; Cabello-Verrugio, Claudio; Santander, Cristian; Brandan, Enrique

    2010-01-01

    Skeletal muscle differentiation is strongly inhibited by transforming growth factor type β (TGF-β), although muscle formation as well as regeneration normally occurs in an environment rich in this growth factor. In this study, we evaluated the role of intracellular regulatory Smads proteins as well as TGF-β-receptors (TGF-β-Rs) during skeletal muscle differentiation. We found a decrease of TGF-β signaling during differentiation. This phenomenon is explained by a decline in the levels of the regulatory proteins Smad-2, -3, and -4, a decrease in the phosphorylation of Smad-2 and lost of nuclear translocation of Smad-3 and -4 in response to TGF-β. No change in the levels and inhibitory function of Smad-7 was observed. In contrast, we found that TGF-β-R type I (TGF-β-RI) and type II (TGF-β-RII) increased on the cell surface during skeletal muscle differentiation. To analyze the direct role of the serine/threonine kinase activities of TGF-β-Rs, we used the specific inhibitor SB 431542 and the dominant-negative form of TGF-β-RII lacking the cytoplasmic domain. The TGF-β-Rs were important for successful muscle formation, determined by the induction of myogenin, creatine kinase activity, and myosin. Silencing of Smad-2/3 expression by specific siRNA treatments accelerated myogenin, myosin expression, and myotube formation; although when SB 431542 was present inhibition in myosin induction and myotube formation was observed, suggesting that these last steps of skeletal muscle differentiation require active TGF-β-Rs. These results suggest that both down-regulation of Smad regulatory proteins and cell signaling through the TGF-β receptors independent of Smad proteins are essential for skeletal muscle differentiation.

  10. TGF-{beta} receptors, in a Smad-independent manner, are required for terminal skeletal muscle differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Droguett, Rebeca; Cabello-Verrugio, Claudio; Santander, Cristian [Centro de Regulacion Celular y Patologia, Centro de Regeneracion y Envejecimiento (CARE), Departamento de Biologia Celular y Molecular, MIFAB, Pontificia Universidad Catolica de Chile, Santiago (Chile); Brandan, Enrique, E-mail: ebrandan@bio.puc.cl [Centro de Regulacion Celular y Patologia, Centro de Regeneracion y Envejecimiento (CARE), Departamento de Biologia Celular y Molecular, MIFAB, Pontificia Universidad Catolica de Chile, Santiago (Chile)

    2010-09-10

    Skeletal muscle differentiation is strongly inhibited by transforming growth factor type {beta} (TGF-{beta}), although muscle formation as well as regeneration normally occurs in an environment rich in this growth factor. In this study, we evaluated the role of intracellular regulatory Smads proteins as well as TGF-{beta}-receptors (TGF-{beta}-Rs) during skeletal muscle differentiation. We found a decrease of TGF-{beta} signaling during differentiation. This phenomenon is explained by a decline in the levels of the regulatory proteins Smad-2, -3, and -4, a decrease in the phosphorylation of Smad-2 and lost of nuclear translocation of Smad-3 and -4 in response to TGF-{beta}. No change in the levels and inhibitory function of Smad-7 was observed. In contrast, we found that TGF-{beta}-R type I (TGF-{beta}-RI) and type II (TGF-{beta}-RII) increased on the cell surface during skeletal muscle differentiation. To analyze the direct role of the serine/threonine kinase activities of TGF-{beta}-Rs, we used the specific inhibitor SB 431542 and the dominant-negative form of TGF-{beta}-RII lacking the cytoplasmic domain. The TGF-{beta}-Rs were important for successful muscle formation, determined by the induction of myogenin, creatine kinase activity, and myosin. Silencing of Smad-2/3 expression by specific siRNA treatments accelerated myogenin, myosin expression, and myotube formation; although when SB 431542 was present inhibition in myosin induction and myotube formation was observed, suggesting that these last steps of skeletal muscle differentiation require active TGF-{beta}-Rs. These results suggest that both down-regulation of Smad regulatory proteins and cell signaling through the TGF-{beta} receptors independent of Smad proteins are essential for skeletal muscle differentiation.

  11. IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively

    DEFF Research Database (Denmark)

    Sichien, Dorine; Scott, Charlotte L; Martens, Liesbet

    2016-01-01

    Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the ide...

  12. Characterisation of cell cycle arrest and terminal differentiation in a maximally proliferative human epithelial tissue: Lessons from the human hair follicle matrix.

    Science.gov (United States)

    Purba, Talveen S; Brunken, Lars; Peake, Michael; Shahmalak, Asim; Chaves, Asuncion; Poblet, Enrique; Ceballos, Laura; Gandarillas, Alberto; Paus, Ralf

    2017-09-01

    Human hair follicle (HF) growth and hair shaft formation require terminal differentiation-associated cell cycle arrest of highly proliferative matrix keratinocytes. However, the regulation of this complex event remains unknown. CIP/KIP family member proteins (p21 CIP1 , p27 KIP1 and p57 KIP2 ) regulate cell cycle progression/arrest, endoreplication, differentiation and apoptosis. Since they have not yet been adequately characterized in the human HF, we asked whether and where CIP/KIP proteins localise in the human hair matrix and pre-cortex in relation to cell cycle activity and HF-specific epithelial cell differentiation that is marked by keratin 85 (K85) protein expression. K85 expression coincided with loss or reduction in cell cycle activity markers, including in situ DNA synthesis (EdU incorporation), Ki-67, phospho-histone H3 and cyclins A and B1, affirming a post-mitotic state of pre-cortical HF keratinocytes. Expression of CIP/KIP proteins was found abundantly within the proliferative hair matrix, concomitant with a role in cell cycle checkpoint control. p21 CIP1 , p27 KIP1 and cyclin E persisted within post-mitotic keratinocytes of the pre-cortex, whereas p57 KIP2 protein decreased but became nuclear. These data imply a supportive role for CIP/KIP proteins in maintaining proliferative arrest, differentiation and anti-apoptotic pathways, promoting continuous hair bulb growth and hair shaft formation in anagen VI. Moreover, post-mitotic hair matrix regions contained cells with enlarged nuclei, and DNA in situ hybridisation showed cells that were >2N in the pre-cortex. This suggests that CIP/KIP proteins might counterbalance cyclin E to control further rounds of DNA replication in a cell population that has a propensity to become tetraploid. These data shed new light on the in situ-biography of human hair matrix keratinocytes on their path of active cell cycling, arrest and terminal differentiation, and showcase the human HF as an excellent, clinically

  13. Genome-wide mapping of Sox6 binding sites in skeletal muscle reveals both direct and indirect regulation of muscle terminal differentiation by Sox6

    Directory of Open Access Journals (Sweden)

    An Chung-Il

    2011-10-01

    Full Text Available Abstract Background Sox6 is a multi-faceted transcription factor involved in the terminal differentiation of many different cell types in vertebrates. It has been suggested that in mice as well as in zebrafish Sox6 plays a role in the terminal differentiation of skeletal muscle by suppressing transcription of slow fiber specific genes. In order to understand how Sox6 coordinately regulates the transcription of multiple fiber type specific genes during muscle development, we have performed ChIP-seq analyses to identify Sox6 target genes in mouse fetal myotubes and generated muscle-specific Sox6 knockout (KO mice to determine the Sox6 null muscle phenotype in adult mice. Results We have identified 1,066 Sox6 binding sites using mouse fetal myotubes. The Sox6 binding sites were found to be associated with slow fiber-specific, cardiac, and embryonic isoform genes that are expressed in the sarcomere as well as transcription factor genes known to play roles in muscle development. The concurrently performed RNA polymerase II (Pol II ChIP-seq analysis revealed that 84% of the Sox6 peak-associated genes exhibited little to no binding of Pol II, suggesting that the majority of the Sox6 target genes are transcriptionally inactive. These results indicate that Sox6 directly regulates terminal differentiation of muscle by affecting the expression of sarcomere protein genes as well as indirectly through influencing the expression of transcription factors relevant to muscle development. Gene expression profiling of Sox6 KO skeletal and cardiac muscle revealed a significant increase in the expression of the genes associated with Sox6 binding. In the absence of the Sox6 gene, there was dramatic upregulation of slow fiber-specific, cardiac, and embryonic isoform gene expression in Sox6 KO skeletal muscle and fetal isoform gene expression in Sox6 KO cardiac muscle, thus confirming the role Sox6 plays as a transcriptional suppressor in muscle development

  14. The role of p38 MAP kinase and c-Jun N-terminal protein kinase signaling in the differentiation and apoptosis of immortalized neural stem cells

    International Nuclear Information System (INIS)

    Yang, Se-Ran; Cho, Sung-Dae; Ahn, Nam-Shik; Jung, Ji-Won; Park, Joon-Suk; Jo, Eun-Hye; Hwang, Jae-Woong; Kim, Sung-Hoon; Lee, Bong-Hee; Kang, Kyung-Sun; Lee, Yong-Soon

    2005-01-01

    The two distinct members of the mitogen-activated protein (MAP) kinase family c-Jun N-terminal protein kinase (JNK) and p38 MAP kinase, play an important role in central nervous system (CNS) development and differentiation. However, their role and functions are not completely understood in CNS. To facilitate in vitro study, we have established an immortal stem cell line using SV40 from fetal rat embryonic day 17. In these cells, MAP kinase inhibitors (SP600125, SB202190, and PD98059) were treated for 1, 24, 48, and 72 h to examine the roles of protein kinases. Early inhibition of JNK did not alter phenotypic or morphological changes of immortalized cells, however overexpression of Bax and decrease of phosphorylated AKT was observed. The prolonged inhibition of JNK induced polyploidization of immortalized cells, and resulted in differentiation and inhibition of cell proliferation. Moreover, JNK and p38 MAP kinase but not ERK1/2 was activated, and p21, p53, and Bax were overexpressed by prolonged inhibition of JNK. These results indicate that JNK and p38 MAP kinase could play dual roles on cell survival and apoptosis. Furthermore, this established cell line could facilitate study of the role of JNK and p38 MAP kinase on CNS development or differentiation/apoptosis

  15. Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import

    Directory of Open Access Journals (Sweden)

    Fowke Keith R

    2005-10-01

    mutant infection, even though they displayed various low levels of nucleus-associated viral DNA, suggesting that these C-terminal mutants also impaired viral DNA integration ability. Conclusion All of these results indicate that, in addition to being involved in HIV-1 reverse transcription and integration, the C-terminal tri-lysine regions of IN also contribute to efficient viral DNA nuclear import during the early stage of HIV-1 replication.

  16. Energetically efficient proportional-integral-differential (PID) control of wake vortices behind a circular cylinder

    International Nuclear Information System (INIS)

    Das, Pramode K; Mathew, Sam; Shaiju, A J; Patnaik, B S V

    2016-01-01

    The control of vortex shedding behind a circular cylinder is a precursor to a wide range of external shear flow problems in engineering, in particular the flow-induced vibrations. In the present study, numerical simulation of an energetically efficient active flow control strategy is proposed, for the control of wake vortices behind a circular cylinder at a low Reynolds number of 100. The fluid is assumed to be incompressible and Newtonian with negligible variation in properties. Reflectionally symmetric controllers are designed such that, they are located on a small sector of the cylinder over which, tangential sliding mode control is imparted. In the field of modern controls, proportional (P), integral (I) and differential (D) control strategies and their numerous combinations are extremely popular in industrial practice. To impart suitable control actuation, the vertically varying lift force on the circular cylinder, is synthesised for the construction of an error term. Four different types of controllers considered in the present study are, P, I, PI and PID. These controllers are evaluated for their energetic efficiency and performance. A linear quadratic optimal control problem is formulated, to minimise the cost functional. By performing detailed simulations, it was observed that, the system is energetically efficient, even when the twin eddies are still persisting behind the circular cylinder. To assess the adaptability of the controllers, the actuators were switched on and off to study their dynamic response. (paper)

  17. Environmental policy and the energy efficiency of vertically differentiated consumer products

    International Nuclear Information System (INIS)

    Brzeskot, Magdalena; Haupt, Alexander

    2013-01-01

    We analyse optimal environmental policies in a market that is vertically differentiated in terms of the energy efficiency of products. Considering energy taxes, subsidies to firms for investment in more eco-friendly products, and product standards, we are particularly interested in how distributional goals in addition to environmental goals shape the choice of policy instruments. We find that an industry-friendly government levies an energy tax to supplement a lax product standard, but shies away from subsidies to firms. By contrast, a consumer-friendly government relies heavily on a strict product standard and additionally implements a moderate subsidy to firms, but avoids energy taxes. - Highlights: ► We analyse how distributional goals shape environmental policy. ► Firms invest in the energy efficiency of their products and compete in prices. ► An industry-friendly government implements an energy tax and a lax product standard. ► A consumer-friendly government chooses a subsidy to firms instead of an energy tax. ► A consumer-friendly government implements a strict energy efficiency standard

  18. Highly efficient transition metal-free coupling of acid chlorides with terminal alkynes in [bmim]Br: A rapid route to access ynones using MgCl2

    Directory of Open Access Journals (Sweden)

    Mohammad Navid Soltani Rad

    2018-03-01

    Full Text Available A simple, mild, highly efficient and transition metal-free protocol for synthesis of ynones in an ionic liquid is described. In this approach, the coupling reaction of different acid chlorides with terminal alkynes was efficiently carried out using 0.05 mol% MgCl2 in the presence of triethylamine in [bmim]Br at room temperature to afford the corresponding ynones in good to excellent yields. This method is highly efficient for various acid chlorides and alkynes including aliphatic, aromatic, and heteroaromatic substrates bearing different functional groups. The influence of some parameters in this reaction including type of ionic liquid, base and catalyst has been discussed.

  19. Can Differentiated Production Planning and Control enable both Responsiveness and Efficiency in Food Production?

    Directory of Open Access Journals (Sweden)

    Anita Romsdal

    2014-07-01

    Full Text Available This paper addresses the complex production planning and control (PPC challenges in food supply chains. The study illustrates how food producers' traditional make‐to‐stock (MTS approach is not well suited to meet the trends of increasing product variety, higher demand uncertainty, increasing sales of fresh food products and more demanding customers. The paper proposes a framework for differentiated PPC that combines MTS with make‐to‐order (MTO.The framework matches products with the most appropriate PPC approaches and buffering techniques depending on market and product characteristics. The core idea is to achieve more volume flexibility in the production system by exploiting favourable product and market characteristics (high demand predictability, long customer order leadtime allowances and low product perishability. A case study is used to demonstrate how the framework can enable food producers to achieve efficiency in production, inventory and PPC processes – and simultaneously be responsive to market requirements.

  20. Differential recognition of terminal extracellular Plasmodium falciparum VAR2CSA domains by sera from multigravid, malaria-exposed Malian women.

    Science.gov (United States)

    Travassos, Mark A; Coulibaly, Drissa; Bailey, Jason A; Niangaly, Amadou; Adams, Matthew; Nyunt, Myaing M; Ouattara, Amed; Lyke, Kirsten E; Laurens, Matthew B; Pablo, Jozelyn; Jasinskas, Algis; Nakajima, Rie; Berry, Andrea A; Takala-Harrison, Shannon; Kone, Abdoulaye K; Kouriba, Bourema; Rowe, J Alexandra; Doumbo, Ogobara K; Thera, Mahamadou A; Laufer, Miriam K; Felgner, Philip L; Plowe, Christopher V

    2015-06-01

    The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediates parasite sequestration in small capillaries through tissue-specific cytoadherence. The best characterized of these proteins is VAR2CSA, which is expressed on the surface of infected erythrocytes that bind to chondroitin sulfate in the placental matrix. Antibodies to VAR2CSA prevent placental cytoadherence and protect against placental malaria. The size and complexity of the VAR2CSA protein pose challenges for vaccine development, but smaller constitutive domains may be suitable for subunit vaccine development. A protein microarray was printed to include five overlapping fragments of the 3D7 VAR2CSA extracellular region. Malian women with a history of at least one pregnancy had antibody recognition of four of these fragments and had stronger reactivity against the two distal fragments than did nulliparous women, children, and men from Mali, suggesting that the C-terminal extracellular VAR2CSA domains are a potential focus of protective immunity. With carefully chosen sera from longitudinal studies of pregnant women, this approach has the potential to identify seroreactive VAR2CSA domains associated with protective immunity against pregnancy-associated malaria. © The American Society of Tropical Medicine and Hygiene.

  1. A Flexible, Efficient Binomial Mixed Model for Identifying Differential DNA Methylation in Bisulfite Sequencing Data

    Science.gov (United States)

    Lea, Amanda J.

    2015-01-01

    Identifying sources of variation in DNA methylation levels is important for understanding gene regulation. Recently, bisulfite sequencing has become a popular tool for investigating DNA methylation levels. However, modeling bisulfite sequencing data is complicated by dramatic variation in coverage across sites and individual samples, and because of the computational challenges of controlling for genetic covariance in count data. To address these challenges, we present a binomial mixed model and an efficient, sampling-based algorithm (MACAU: Mixed model association for count data via data augmentation) for approximate parameter estimation and p-value computation. This framework allows us to simultaneously account for both the over-dispersed, count-based nature of bisulfite sequencing data, as well as genetic relatedness among individuals. Using simulations and two real data sets (whole genome bisulfite sequencing (WGBS) data from Arabidopsis thaliana and reduced representation bisulfite sequencing (RRBS) data from baboons), we show that our method provides well-calibrated test statistics in the presence of population structure. Further, it improves power to detect differentially methylated sites: in the RRBS data set, MACAU detected 1.6-fold more age-associated CpG sites than a beta-binomial model (the next best approach). Changes in these sites are consistent with known age-related shifts in DNA methylation levels, and are enriched near genes that are differentially expressed with age in the same population. Taken together, our results indicate that MACAU is an efficient, effective tool for analyzing bisulfite sequencing data, with particular salience to analyses of structured populations. MACAU is freely available at www.xzlab.org/software.html. PMID:26599596

  2. A novel Atoh1 "self-terminating" mouse model reveals the necessity of proper Atoh1 level and duration for hair cell differentiation and viability.

    Directory of Open Access Journals (Sweden)

    Ning Pan

    Full Text Available Atonal homolog1 (Atoh1 is a bHLH transcription factor essential for inner ear hair cell differentiation. Targeted expression of Atoh1 at various stages in development can result in hair cell differentiation in the ear. However, the level and duration of Atoh1 expression required for proper hair cell differentiation and maintenance remain unknown. We generated an Atoh1 conditional knockout (CKO mouse line using Tg(Atoh1-cre, in which the cre expression is driven by an Atoh1 enhancer element that is regulated by Atoh1 protein to "self-terminate" its expression. The mutant mice show transient, limited expression of Atoh1 in all hair cells in the ear. In the organ of Corti, reduction and delayed deletion of Atoh1 result in progressive loss of almost all the inner hair cells and the majority of the outer hair cells within three weeks after birth. The remaining cells express hair cell marker Myo7a and attract nerve fibers, but do not differentiate normal stereocilia bundles. Some Myo7a-positive cells persist in the cochlea into adult stages in the position of outer hair cells, flanked by a single row of pillar cells and two to three rows of disorganized Deiters cells. Gene expression analyses of Atoh1, Barhl1 and Pou4f3, genes required for survival and maturation of hair cells, reveal earlier and higher expression levels in the inner compared to the outer hair cells. Our data show that Atoh1 is crucial for hair cell mechanotransduction development, viability, and maintenance and also suggest that Atoh1 expression level and duration may play a role in inner vs. outer hair cell development. These genetically engineered Atoh1 CKO mice provide a novel model for establishing critical conditions needed to regenerate viable and functional hair cells with Atoh1 therapy.

  3. Assessing the efficiency of Wolbachia driven Aedes mosquito suppression by delay differential equations.

    Science.gov (United States)

    Huang, Mugen; Luo, Jiaowan; Hu, Linchao; Zheng, Bo; Yu, Jianshe

    2017-12-14

    To suppress wild population of Aedes mosquitoes, the primary transmission vector of life-threatening diseases such as dengue, malaria, and Zika, an innovative strategy is to release male mosquitoes carrying the bacterium Wolbachia into natural areas to drive female sterility by cytoplasmic incompatibility. We develop a model of delay differential equations, incorporating the strong density restriction in the larval stage, to assess the delicate impact of life table parameters on suppression efficiency. Through mathematical analysis, we find the sufficient and necessary condition for global stability of the complete suppression state. This condition, combined with the experimental data for Aedes albopictus population in Guangzhou, helps us predict a large range of releasing intensities for suppression success. In particular, we find that if the number of released infected males is no less than four times the number of mosquitoes in wild areas, then the mosquito density in the peak season can be reduced by 95%. We introduce an index to quantify the dependence of suppression efficiency on parameters. The invariance of some quantitative properties of the index values under various perturbations of the same parameter justifies the applicability of this index, and the robustness of our modeling approach. The index yields a ranking of the sensitivity of all parameters, among which the adult mortality has the highest sensitivity and is considerably more sensitive than the natural larvae mortality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Differential structural properties of GLP-1 and exendin-4 determine their relative affinity for the GLP-1 receptor N-terminal extracellular domain.

    Science.gov (United States)

    Runge, Steffen; Schimmer, Susann; Oschmann, Jan; Schiødt, Christine Bruun; Knudsen, Sanne Möller; Jeppesen, Claus Bekker; Madsen, Kjeld; Lau, Jesper; Thøgersen, Henning; Rudolph, Rainer

    2007-05-15

    Glucagon-like peptide-1 (GLP-1) and exendin-4 (Ex4) are homologous peptides with established potential for treatment of type 2 diabetes. They bind and activate the pancreatic GLP-1 receptor (GLP-1R) with similar affinity and potency and thereby promote insulin secretion in a glucose-dependent manner. GLP-1R belongs to family B of the seven transmembrane G-protein coupled receptors. The N-terminal extracellular domain (nGLP-1R) is a ligand binding domain with differential affinity for Ex4 and GLP-1: low affinity for GLP-1 and high affinity for exendin-4. The superior affinity of nGLP-1R for Ex4 was previously explained by an additional interaction between nGLP-1R and the C-terminal Trp-cage of Ex4. In this study we have combined biophysical and pharmacological approaches thus relating structural properties of the ligands in solution to their relative binding affinity for nGLP-1R. We used both a tracer competition assay and ligand-induced thermal stabilization of nGLP-1R to measure the relative affinity of full length, truncated, and chimeric ligands for soluble refolded nGLP-1R. The ligands in solution and the conformational consequences of ligand binding to nGLP-1R were characterized by circular dichroism and fluorescence spectroscopy. We found a correlation between the helical content of the free ligands and their relative binding affinity for nGLP-1R, supporting the hypothesis that the ligands are helical at least in the segment that binds to nGLP-1R. The Trp-cage of Ex4 was not necessary to maintain a superior helicity of Ex4 compared to GLP-1. The results suggest that the differential affinity of nGLP-1R is explained almost entirely by divergent residues in the central part of the ligands: Leu10-Gly30 of Ex4 and Val16-Arg36 of GLP-1. In view of our results it appears that the Trp-cage plays only a minor role for the interaction between Ex4 and nGLP-1R and for the differential affinity of nGLP-1R for GLP-1 and Ex4.

  5. Highly efficient synthetic method onpyroacm resin using the boc SPPS protocol for C-terminal cysteine peptide synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Juvekar, Vinayak; Kim, Kang Tae; Gong, Young Dae [Innovative Drug Library Research Center, Dept. of Chemistry, College of Science, Dongguk University, Seoul (Korea, Republic of)

    2017-01-15

    A very effective process on Pyroacm resin was developed for solid-phase peptide synthesis (SPPS) of C-terminal cysteine and cysteine ester peptides. The process uses cysteine side chain anchoring to the Pyroacm resin and the Boc protocol for SPPS. The Pyroacm resin showed remarkable stability under standard trifluoromethanesulfonic acid (TFMSA) cleavage condition. TFMSA cleavage of protecting groups generates a peptide-linked resin, which can be subjected to peptide modification reactions. Finally, the peptide can be cleaved from the resin using methoxycarbonylsulfenyl chloride. The utility of this protocol was demonstrated by its applications to the synthesis of model peptides, key intermediates in the preparation of natural products riparin 1.2 and a-factor.

  6. Lysophospholipid Receptors Are Differentially Expressed in Rat Terminal Schwann Cells, As Revealed by a Single Cell RT-PCR and In Situ Hybridization

    International Nuclear Information System (INIS)

    Kobashi, Hiroaki; Yaoi, Takeshi; Oda, Ryo; Okajima, Seiichiro; Fujiwara, Hiroyoshi; Kubo, Toshikazu; Fushiki, Shinji

    2006-01-01

    Terminal Schwann cells (TSCs) that cover motor neuron terminals, are known to play an important role in maintaining neuromuscular junctions, as well as in the repair process after nerve injury. However, the molecular characteristics of TSCs remain unknown, because of the difficulties in analyzing them due to their paucity. By using our previously reported method of selectively and efficiently collecting TSCs, we have analyzed the difference in expression patterns of lysophospholipid (LPL) receptor genes (LPA 1 , LPA 2 , LPA 3 , S1P 1 , S1P 2 , S1P 3 , S1P 4 , and S1P 5 ) between TSCs and myelinating Schwann cells (MSCs). LPL, which includes lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), is the bioactive lipid that induces a myriad of cellular responses through specific members of G-protein coupled receptors for LPA. It turned out that LPA 3 was expressed only in TSCs, whereas S1P 1 was expressed in TSCs and skeletal muscle, but not in MSCs. Other types of LPL receptor genes, including LPA 1 , S1P 2 , S1P 3 , S1P 4 , were expressed in both types of Schwann cells. None of the LPL receptor gene family showed MSCs-specific expression

  7. Numerical simulations: Toward the design of 27.6% efficient four-terminal semi-transparent perovskite/SiC passivated rear contact silicon tandem solar cell

    Science.gov (United States)

    Pandey, Rahul; Chaujar, Rishu

    2016-12-01

    In this work, a novel four-terminal perovskite/SiC-based rear contact silicon tandem solar cell device has been proposed and simulated to achieve 27.6% power conversion efficiency (PCE) under single AM1.5 illumination. 20.9% efficient semitransparent perovskite top subcell has been used for perovskite/silicon tandem architecture. The tandem structure of perovskite-silicon solar cells is a promising method to achieve efficient solar energy conversion at low cost. In the four-terminal tandem configuration, the cells are connected independently and hence avoids the need for current matching between top and bottom subcell, thus giving greater design flexibility. The simulation analysis shows, PCE of 27.6% and 22.4% with 300 μm and 10 μm thick rear contact Si bottom subcell, respectively. This is a substantial improvement comparing to transparent perovskite solar cell and c-Si solar cell operated individually. The impact of perovskite layer thickness, monomolecular, bimolecular, and trimolecular recombination have also been obtained on the performance of perovskite top subcell. Reported PCEs of 27.6% and 22.4% are 1.25 times and 1.42 times higher as compared to experimentally available efficiencies of 22.1% and 15.7% in 300 μm and 10 μm thick stand-alone silicon solar cell devices, respectively. The presence of SiC significantly suppressed the interface recombination in bottom silicon subcell. Detailed realistic technology computer aided design (TCAD) analysis has been performed to predict the behaviour of the device.

  8. Genes encoded within 8q24 on the amplicon of a large extrachromosomal element are selectively repressed during the terminal differentiation of HL-60 cells.

    Science.gov (United States)

    Hirano, Tetsuo; Ike, Fumio; Murata, Takehide; Obata, Yuichi; Utiyama, Hiroyasu; Yokoyama, Kazunari K

    2008-04-02

    Human acute myeloblastic leukemia HL-60 cells become resistant to differentiation during long-term cultivation. After 150 passages, double minute chromosomes (dmins) found in early-passaged cells are replaced by large extrachromosomal elements (LEEs). In a DNA library derived from a purified fraction of LEEs, 12.6% (23/183) of clones were assigned to 8q24 and 9.2% (17/183) were assigned to 14q11 in the human genome. Fluorescence in situ hybridization (FISH) revealed a small aberrant chromosome, which had not been found in early-passaged cells, in addition to the purified LEEs. We determined that each LEE consisted of six discontinuous segments in a region that extended for 4.4Mb over the 8q24 locus. Five genes, namely, Myc (a proto-oncogene), NSMCE2 (for a SUMO ligase), CCDC26 (for a retinoic acid-dependent modulator of myeloid differentiation), TRIB1 (for a regulator of MAPK kinase) and LOC389637 (for a protein of unknown function), were encoded by the amplicon. Breaks in the chromosomal DNA within the amplicon were found in the NSMCE2 and CCDC26 genes. The discontinuous structure of the amplicon unit of the LEEs was identical with that of dmins in HL-60 early-passaged cells. The difference between them seemed, predominantly, to be the number (10-15 copies per LEE versus 2 or 3 copies per dmin) of constituent units. Expression of the Myc, NSMCE2, CCDC26 and LOC389637 and TRIB1 genes was constitutive in all lines of HL-60 cells and that of the first four genes was repressed during the terminal differentiation of early-passaged HL-60 cells. We also detected abnormal transcripts of CCDC26. Our results suggest that these genes were selected during the development of amplicons. They might be amplified and, sometimes, truncated to contribute to the maintenance of HL-60 cells in an undifferentiated state.

  9. Efficient Nazarov cyclization/Wagner-Meerwein rearrangement terminated by a Cu(II)-promoted oxidation: synthesis of 4-alkylidene cyclopentenones.

    Science.gov (United States)

    Lebœuf, David; Theiste, Eric; Gandon, Vincent; Daifuku, Stephanie L; Neidig, Michael L; Frontier, Alison J

    2013-04-08

    The discovery and elucidation of a new Nazarov cyclization/Wagner-Meerwein rearrangement/oxidation sequence is described that constitutes an efficient strategy for the synthesis of 4-alkylidene cyclopentenones. DFT computations and EPR experiments were conducted to gain further mechanistic insight into the reaction pathways. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Efficient myogenic differentiation of human adipose-derived stem cells by the transduction of engineered MyoD protein

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Min Sun [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Biosystems and Bioengineering Program, University of Science and Technology (UST), Daejeon 305-350 (Korea, Republic of); Mun, Ji-Young [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Kwon, Ohsuk [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Biosystems and Bioengineering Program, University of Science and Technology (UST), Daejeon 305-350 (Korea, Republic of); Kwon, Ki-Sun [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Oh, Doo-Byoung, E-mail: dboh@kribb.re.kr [Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Biosystems and Bioengineering Program, University of Science and Technology (UST), Daejeon 305-350 (Korea, Republic of)

    2013-07-19

    Highlights: •MyoD was engineered to contain protein transduction domain and endosome-disruptive INF7 peptide. •The engineered MyoD-IT showed efficient nuclear targeting through an endosomal escape by INF7 peptide. •By applying MyoD-IT, human adipose-derived stem cells (hASCs) were differentiated into myogenic cells. •hASCs differentiated by applying MyoD-IT fused to myotubes through co-culturing with mouse myoblasts. •Myogenic differentiation using MyoD-IT is a safe method without the concern of altering the genome. -- Abstract: Human adipose-derived stem cells (hASCs) have great potential as cell sources for the treatment of muscle disorders. To provide a safe method for the myogenic differentiation of hASCs, we engineered the MyoD protein, a key transcription factor for myogenesis. The engineered MyoD (MyoD-IT) was designed to contain the TAT protein transduction domain for cell penetration and the membrane-disrupting INF7 peptide, which is an improved version of the HA2 peptide derived from influenza. MyoD-IT showed greatly improved nuclear targeting ability through an efficient endosomal escape induced by the pH-sensitive membrane disruption of the INF7 peptide. By applying MyoD-IT to a culture, hASCs were efficiently differentiated into long spindle-shaped myogenic cells expressing myosin heavy chains. Moreover, these cells differentiated by an application of MyoD-IT fused to myotubes with high efficiency through co-culturing with mouse C2C12 myoblasts. Because internalized proteins can be degraded in cells without altering the genome, the myogenic differentiation of hASCs using MyoD-IT would be a safe and clinically applicable method.

  11. Efficient myogenic differentiation of human adipose-derived stem cells by the transduction of engineered MyoD protein

    International Nuclear Information System (INIS)

    Sung, Min Sun; Mun, Ji-Young; Kwon, Ohsuk; Kwon, Ki-Sun; Oh, Doo-Byoung

    2013-01-01

    Highlights: •MyoD was engineered to contain protein transduction domain and endosome-disruptive INF7 peptide. •The engineered MyoD-IT showed efficient nuclear targeting through an endosomal escape by INF7 peptide. •By applying MyoD-IT, human adipose-derived stem cells (hASCs) were differentiated into myogenic cells. •hASCs differentiated by applying MyoD-IT fused to myotubes through co-culturing with mouse myoblasts. •Myogenic differentiation using MyoD-IT is a safe method without the concern of altering the genome. -- Abstract: Human adipose-derived stem cells (hASCs) have great potential as cell sources for the treatment of muscle disorders. To provide a safe method for the myogenic differentiation of hASCs, we engineered the MyoD protein, a key transcription factor for myogenesis. The engineered MyoD (MyoD-IT) was designed to contain the TAT protein transduction domain for cell penetration and the membrane-disrupting INF7 peptide, which is an improved version of the HA2 peptide derived from influenza. MyoD-IT showed greatly improved nuclear targeting ability through an efficient endosomal escape induced by the pH-sensitive membrane disruption of the INF7 peptide. By applying MyoD-IT to a culture, hASCs were efficiently differentiated into long spindle-shaped myogenic cells expressing myosin heavy chains. Moreover, these cells differentiated by an application of MyoD-IT fused to myotubes with high efficiency through co-culturing with mouse C2C12 myoblasts. Because internalized proteins can be degraded in cells without altering the genome, the myogenic differentiation of hASCs using MyoD-IT would be a safe and clinically applicable method

  12. Efficient and reproducible myogenic differentiation from human iPS cells: prospects for modeling Miyoshi Myopathy in vitro.

    Directory of Open Access Journals (Sweden)

    Akihito Tanaka

    Full Text Available The establishment of human induced pluripotent stem cells (hiPSCs has enabled the production of in vitro, patient-specific cell models of human disease. In vitro recreation of disease pathology from patient-derived hiPSCs depends on efficient differentiation protocols producing relevant adult cell types. However, myogenic differentiation of hiPSCs has faced obstacles, namely, low efficiency and/or poor reproducibility. Here, we report the rapid, efficient, and reproducible differentiation of hiPSCs into mature myocytes. We demonstrated that inducible expression of myogenic differentiation1 (MYOD1 in immature hiPSCs for at least 5 days drives cells along the myogenic lineage, with efficiencies reaching 70-90%. Myogenic differentiation driven by MYOD1 occurred even in immature, almost completely undifferentiated hiPSCs, without mesodermal transition. Myocytes induced in this manner reach maturity within 2 weeks of differentiation as assessed by marker gene expression and functional properties, including in vitro and in vivo cell fusion and twitching in response to electrical stimulation. Miyoshi Myopathy (MM is a congenital distal myopathy caused by defective muscle membrane repair due to mutations in DYSFERLIN. Using our induced differentiation technique, we successfully recreated the pathological condition of MM in vitro, demonstrating defective membrane repair in hiPSC-derived myotubes from an MM patient and phenotypic rescue by expression of full-length DYSFERLIN (DYSF. These findings not only facilitate the pathological investigation of MM, but could potentially be applied in modeling of other human muscular diseases by using patient-derived hiPSCs.

  13. Efficient and Reproducible Myogenic Differentiation from Human iPS Cells: Prospects for Modeling Miyoshi Myopathy In Vitro

    Science.gov (United States)

    Tanaka, Akihito; Woltjen, Knut; Miyake, Katsuya; Hotta, Akitsu; Ikeya, Makoto; Yamamoto, Takuya; Nishino, Tokiko; Shoji, Emi; Sehara-Fujisawa, Atsuko; Manabe, Yasuko; Fujii, Nobuharu; Hanaoka, Kazunori; Era, Takumi; Yamashita, Satoshi; Isobe, Ken-ichi; Kimura, En; Sakurai, Hidetoshi

    2013-01-01

    The establishment of human induced pluripotent stem cells (hiPSCs) has enabled the production of in vitro, patient-specific cell models of human disease. In vitro recreation of disease pathology from patient-derived hiPSCs depends on efficient differentiation protocols producing relevant adult cell types. However, myogenic differentiation of hiPSCs has faced obstacles, namely, low efficiency and/or poor reproducibility. Here, we report the rapid, efficient, and reproducible differentiation of hiPSCs into mature myocytes. We demonstrated that inducible expression of myogenic differentiation1 (MYOD1) in immature hiPSCs for at least 5 days drives cells along the myogenic lineage, with efficiencies reaching 70–90%. Myogenic differentiation driven by MYOD1 occurred even in immature, almost completely undifferentiated hiPSCs, without mesodermal transition. Myocytes induced in this manner reach maturity within 2 weeks of differentiation as assessed by marker gene expression and functional properties, including in vitro and in vivo cell fusion and twitching in response to electrical stimulation. Miyoshi Myopathy (MM) is a congenital distal myopathy caused by defective muscle membrane repair due to mutations in DYSFERLIN. Using our induced differentiation technique, we successfully recreated the pathological condition of MM in vitro, demonstrating defective membrane repair in hiPSC-derived myotubes from an MM patient and phenotypic rescue by expression of full-length DYSFERLIN (DYSF). These findings not only facilitate the pathological investigation of MM, but could potentially be applied in modeling of other human muscular diseases by using patient-derived hiPSCs. PMID:23626698

  14. Biophysical and physicochemical methods differentiate highly ligand-efficient human D-amino acid oxidase inhibitors.

    Science.gov (United States)

    Lange, Jos H M; Venhorst, Jennifer; van Dongen, Maria J P; Frankena, Jurjen; Bassissi, Firas; de Bruin, Natasja M W J; den Besten, Cathaline; de Beer, Stephanie B A; Oostenbrink, Chris; Markova, Natalia; Kruse, Chris G

    2011-10-01

    Many early drug research efforts are too reductionist thereby not delivering key parameters such as kinetics and thermodynamics of target-ligand binding. A set of human D-Amino Acid Oxidase (DAAO) inhibitors 1-6 was applied to demonstrate the impact of key biophysical techniques and physicochemical methods in the differentiation of chemical entities that cannot be adequately distinguished on the basis of their normalized potency (ligand efficiency) values. The resulting biophysical and physicochemical data were related to relevant pharmacodynamic and pharmacokinetic properties. Surface Plasmon Resonance data indicated prolonged target-ligand residence times for 5 and 6 as compared to 1-4, based on the observed k(off) values. The Isothermal Titration Calorimetry-derived thermodynamic binding profiles of 1-6 to the DAAO enzyme revealed favorable contributions of both ΔH and ΔS to their ΔG values. Surprisingly, the thermodynamic binding profile of 3 elicited a substantially higher favorable contribution of ΔH to ΔG in comparison with the structurally closely related fused bicyclic acid 4. Molecular dynamics simulations and free energy calculations of 1, 3, and 4 led to novel insights into the thermodynamic properties of the binding process at an atomic level and in the different thermodynamic signatures of 3 and 4. The presented holistic approach is anticipated to facilitate the identification of compounds with best-in-class properties at an early research stage. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  15. CD8αα expression marks terminally differentiated human CD8+ T cells expanded in chronic viral infection

    Directory of Open Access Journals (Sweden)

    Lucy Jane Walker

    2013-08-01

    Full Text Available The T cell co-receptor CD8αβ enhances T cell sensitivity to antigen, however studies indicate CD8αα has the converse effect and acts as a co-repressor. Using a combination of Thymic Leukaemia antigen (TL tetramer, which directly binds CD8αα, anti-CD161 and anti-Vα7.2 antibodies we have been able for the first time to clearly define CD8αα expression on human CD8 T cells subsets. In healthy controls CD8αα is most highly expressed by CD161 bright (CD161++ mucosal associated invariant T (MAIT cells, with CD8αα expression highly restricted to the TCR Vα7.2+ cells of this subset. We also identified CD8αα-expressing populations within the CD161 mid (CD161+ and negative (CD161- non-MAIT CD8 T cell subsets and show TL-tetramer binding to correlate with expression of CD8β at low levels in the context of maintained CD8α expression (CD8α+CD8βlow. In addition, we found CD161-CD8α+CD8βlow populations to be significantly expanded in the peripheral blood of HIV-1 and hepatitis B (mean of 47% and 40% of CD161- T cells respectively infected individuals. Such CD8αα expressing T cells are an effector-memory population (CD45RA-, CCR7-, CD62L- that express markers of activation and maturation (HLA-DR+, CD28-, CD27-, CD57+ and are functionally distinct, expressing greater levels of TNF-α and IFN-γ on stimulation and perforin at rest than their CD8α+CD8βhigh counterparts. Antigen-specific T cells in HLA-B*4201+HIV-1 infected patients are found within both the CD161-CD8α+CD8βhigh and CD161-CD8α+CD8βlow populations. Overall we have clearly defined CD8αα expressing human T cell subsets using the TL-tetramer, and have demonstrated CD161-CD8α+CD8βlow populations, highly expanded in disease settings, to co-express CD8αβ and CD8αα. Co-expression of CD8αα on CD8αβ T cells may impact on their overall function in-vivo and contribute to the distinctive phenotype of highly differentiated populations in HBV and HIV-1 infection.

  16. Proneural transcription factor Atoh1 drives highly efficient differentiation of human pluripotent stem cells into dopaminergic neurons.

    Science.gov (United States)

    Sagal, Jonathan; Zhan, Xiping; Xu, Jinchong; Tilghman, Jessica; Karuppagounder, Senthilkumar S; Chen, Li; Dawson, Valina L; Dawson, Ted M; Laterra, John; Ying, Mingyao

    2014-08-01

    Human pluripotent stem cells (PSCs) are a promising cell resource for various applications in regenerative medicine. Highly efficient approaches that differentiate human PSCs into functional lineage-specific neurons are critical for modeling neurological disorders and testing potential therapies. Proneural transcription factors are crucial drivers of neuron development and hold promise for driving highly efficient neuronal conversion in PSCs. Here, we study the functions of proneural transcription factor Atoh1 in the neuronal differentiation of PSCs. We show that Atoh1 is induced during the neuronal conversion of PSCs and that ectopic Atoh1 expression is sufficient to drive PSCs into neurons with high efficiency. Atoh1 induction, in combination with cell extrinsic factors, differentiates PSCs into functional dopaminergic (DA) neurons with >80% purity. Atoh1-induced DA neurons recapitulate key biochemical and electrophysiological features of midbrain DA neurons, the degeneration of which is responsible for clinical symptoms in Parkinson's disease (PD). Atoh1-induced DA neurons provide a reliable disease model for studying PD pathogenesis, such as neurotoxin-induced neurodegeneration in PD. Overall, our results determine the role of Atoh1 in regulating neuronal differentiation and neuron subtype specification of human PSCs. Our Atoh1-mediated differentiation approach will enable large-scale applications of PD patient-derived midbrain DA neurons in mechanistic studies and drug screening for both familial and sporadic PD. ©AlphaMed Press.

  17. Efficiently and easily integrating differential equations with JiTCODE, JiTCDDE, and JiTCSDE

    Science.gov (United States)

    Ansmann, Gerrit

    2018-04-01

    We present a family of Python modules for the numerical integration of ordinary, delay, or stochastic differential equations. The key features are that the user enters the derivative symbolically and it is just-in-time-compiled, allowing the user to efficiently integrate differential equations from a higher-level interpreted language. The presented modules are particularly suited for large systems of differential equations such as those used to describe dynamics on complex networks. Through the selected method of input, the presented modules also allow almost complete automatization of the process of estimating regular as well as transversal Lyapunov exponents for ordinary and delay differential equations. We conceptually discuss the modules' design, analyze their performance, and demonstrate their capabilities by application to timely problems.

  18. Differential efficiencies of dip-net sampling versus sampling surface-floating pupal exuviae in a biodiversity survey of Chironomidae

    Directory of Open Access Journals (Sweden)

    Leonard Charles Ferrington Jr

    2014-12-01

    Full Text Available Relative efficiencies of standard dip-net sampling (SDN versus collections of surface-floating pupal exuviae (SFPE were determined for detecting Chironomidae at catchment and site scales and at subfamily/tribe-, genus- and species-levels based on simultaneous, equal-effort sampling on a monthly basis for one year during a biodiversity assessment of Bear Run Nature Reserve. Results showed SFPE was more efficient than SDN at catchment scales for detecting both genera and species. At site scales, SDN sampling was more efficient for assessment of a first-order site. No consistent pattern, except for better efficiency of SFPE to detect Orthocladiinae genera, was observed at genus-level for two second-order sites. However, SFPE was consistently more efficient at detecting species of Orthocladiinae, Chironomini and Tanytarsini at the second order sites. SFPE was more efficient at detecting both genera and species at two third-order sites. The differential efficiencies of the two methods are concluded to be related to stream order and size, substrate size, flow and water velocity, depth and habitat heterogeneity, and differential ability to discriminate species among pupal exuviae specimens versus larval specimens. Although both approaches are considered necessary for comprehensive biodiversity assessments of Chironomidae, our results suggest that there is an optimal, but different, allocation of sampling effort for detecting Chironomidae across stream orders and at differing spatial and taxonomic scales.Article submitted 13. August 2014, accepted 31. October 2014, published 22. December 2014.

  19. Efficient differential Fourier-transform spectrometer for precision Sunyaev-Zel'dovich effect measurements

    Science.gov (United States)

    Schillaci, Alessandro; D'Alessandro, Giuseppe; de Bernardis, Paolo; Masi, Silvia; Paiva Novaes, Camila; Gervasi, Massimo; Zannoni, Mario

    2014-05-01

    Context. Precision measurements of the Sunyaev-Zel'dovich effect in clusters of galaxies require excellent rejection of common-mode signals and wide frequency coverage. Aims: We describe an imaging, efficient, differential Fourier transform spectrometer (FTS), optimized for measurements of faint brightness gradients at millimeter wavelengths. Methods: Our instrument is based on a Martin-Puplett interferometer (MPI) configuration. We combined two MPIs working synchronously to use the whole input power. In our implementation the observed sky field is divided into two halves along the meridian, and each half-field corresponds to one of the two input ports of the MPI. In this way, each detector in the FTS focal planes measures the difference in brightness between two sky pixels, symmetrically located with respect to the meridian. Exploiting the high common-mode rejection of the MPI, we can measure low sky brightness gradients over a high isotropic background. Results: The instrument works in the range ~1-20 cm-1 (30-600 GHz), has a maximum spectral resolution 1 / (2 OPD) = 0.063 cm-1 (1.9 GHz), and an unvignetted throughput of 2.3 cm2sr. It occupies a volume of 0.7 × 0.7 × 0.33 m3 and has a weight of 70 kg. This design can be implemented as a cryogenic unit to be used in space, as well as a room-temperature unit working at the focus of suborbital and ground-based mm-wave telescopes. The first in-flight test of the instrument is with the OLIMPO experiment on a stratospheric balloon; a larger implementation is being prepared for the Sardinia radio telescope.

  20. Decomposing price differentials due to ENERGY STARR labels and energy efficiency features in appliances: proxy for market share tracking?

    International Nuclear Information System (INIS)

    Gardner, John; Skumatz, Lisa A.

    2005-01-01

    This paper summarizes recent work using statistical methods to examine the portions of the apparent price differences for a variety of appliances that are attributable to efficiency labels or components of efficient measures. The work stems from research examining progress in market transformation. The goal was to monitor market progress in the premium associated with efficient equipment compared to standard equipment - and potentially track these changes (hopefully, according to logic, declining) over time. However, the incremental cost metric is always confounded by the fact that the 'feature bundle' on appliances and lighting is not consistent ( i.e. , many efficient products are loaded up with other, high-end features). Based on work conducted by the authors some years ago, we adapted statistical models to decompose the price differentials for efficient and standard refrigerators, clothes washers, and dish washers. The authors used site visits and web searches to gather data on appliance prices and features for a set of efficient and standard models. The authors first examined apparent (raw) price differentials between efficient and standard models. Then, using regression techniques to control for differences in features on the measures, the differences attributable to various features - and in particular to energy efficient features and logos - were estimated. The results showed that while the apparent (gross) price differences for efficient measures are high, the percentage and dollar differences decrease dramatically when the price differences statistically attributable to other features of the measure are accounted for. The work illustrates a promising approach for three important applications in program planning and evaluation: tracking market progress within and between states or service territories, using a proxy variable that is less expensive and complicated to measure than direct indicators of sales or market share, identifying appropriate levels for

  1. A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability.

    Directory of Open Access Journals (Sweden)

    Paul W Burridge

    2011-04-01

    Full Text Available The production of cardiomyocytes from human induced pluripotent stem cells (hiPSC holds great promise for patient-specific cardiotoxicity drug testing, disease modeling, and cardiac regeneration. However, existing protocols for the differentiation of hiPSC to the cardiac lineage are inefficient and highly variable. We describe a highly efficient system for differentiation of human embryonic stem cells (hESC and hiPSC to the cardiac lineage. This system eliminated the variability in cardiac differentiation capacity of a variety of human pluripotent stem cells (hPSC, including hiPSC generated from CD34(+ cord blood using non-viral, non-integrating methods.We systematically and rigorously optimized >45 experimental variables to develop a universal cardiac differentiation system that produced contracting human embryoid bodies (hEB with an improved efficiency of 94.7±2.4% in an accelerated nine days from four hESC and seven hiPSC lines tested, including hiPSC derived from neonatal CD34(+ cord blood and adult fibroblasts using non-integrating episomal plasmids. This cost-effective differentiation method employed forced aggregation hEB formation in a chemically defined medium, along with staged exposure to physiological (5% oxygen, and optimized concentrations of mesodermal morphogens BMP4 and FGF2, polyvinyl alcohol, serum, and insulin. The contracting hEB derived using these methods were composed of high percentages (64-89% of cardiac troponin I(+ cells that displayed ultrastructural properties of functional cardiomyocytes and uniform electrophysiological profiles responsive to cardioactive drugs.This efficient and cost-effective universal system for cardiac differentiation of hiPSC allows a potentially unlimited production of functional cardiomyocytes suitable for application to hPSC-based drug development, cardiac disease modeling, and the future generation of clinically-safe nonviral human cardiac cells for regenerative medicine.

  2. Research on the Spatial Differentiation and Driving Factors of Tourism Enterprises’ Efficiency: Chinese Scenic Spots, Travel Agencies, and Hotels

    Directory of Open Access Journals (Sweden)

    Bing Xia

    2018-03-01

    Full Text Available Tourism is an important sustainable industry in the economy that optimizes the industrial structure. Thus, as a core part of this market, tourism enterprises perform a key role in the effective operation of this industry. This paper applies data envelopment analysis (DEA and Malmquist index (MI models to calculate the efficiency of Chinese tourism enterprises between 2005 and 2014. Results showed that: (1 The efficiency and the total factor productivity change index (TFPC of tourism enterprises remained low, and both have decreased. (2 The efficiency of regional tourism enterprises across China cloud be characterized as high in the east region, low in the central region, and high in both northeast and western regions. (3 The efficiency levels of the cities of Beijing and Shanghai were ahead of the country over the period of this study, while Chongqing, Tibet, Qinghai, and Ningxia all possess a number of obvious advantages in the western region. (4 Centers of overall tourism enterprise efficiency mainly moved in a southeast-to-northwest direction over the period of this research. (5 The spatial autocorrelation of tourism enterprise efficiencies is also assessed in this study, and the results show that the comprehensive efficiency (CE of tourism enterprises in southeastern coastal regions of China tended to a certain spatial agglomeration effect, while the correlation between the central region and northern China was not significant. (6 The Geodetector model is applied to analyze the key factors driving the spatial differentiation of tourism enterprise efficiencies, and the results show that the degree of opening to the outside world, potential human capital, and traffic conditions were the most important factors driving spatial differentiation in the efficiency of tourism enterprises.

  3. Efficient femtosecond driven SOX 17 delivery into mouse embryonic stem cells: Differentiation study

    CSIR Research Space (South Africa)

    Thobakgale, Setumo L

    2017-01-01

    Full Text Available (4) 3. Konorov, S.O. et al., The process analytical utility of Raman microspectroscopy in the directed differentiation of human pancreatic insulin-positive cells ( Supporting Information ) Corresponding Authors : This Supporting Information provides...

  4. A pump-free microfluidic 3D perfusion platform for the efficient differentiation of human hepatocyte-like cells.

    Science.gov (United States)

    Ong, Louis Jun Ye; Chong, Lor Huai; Jin, Lin; Singh, Pawan Kumar; Lee, Poh Seng; Yu, Hanry; Ananthanarayanan, Abhishek; Leo, Hwa Liang; Toh, Yi-Chin

    2017-10-01

    The practical application of microfluidic liver models for in vitro drug testing is partly hampered by their reliance on human primary hepatocytes, which are limited in number and have batch-to-batch variation. Human stem cell-derived hepatocytes offer an attractive alternative cell source, although their 3D differentiation and maturation in a microfluidic platform have not yet been demonstrated. We develop a pump-free microfluidic 3D perfusion platform to achieve long-term and efficient differentiation of human liver progenitor cells into hepatocyte-like cells (HLCs). The device contains a micropillar array to immobilize cells three-dimensionally in a central cell culture compartment flanked by two side perfusion channels. Constant pump-free medium perfusion is accomplished by controlling the differential heights of horizontally orientated inlet and outlet media reservoirs. Computational fluid dynamic simulation is used to estimate the hydrostatic pressure heads required to achieve different perfusion flow rates, which are experimentally validated by micro-particle image velocimetry, as well as viability and functional assessments in a primary rat hepatocyte model. We perform on-chip differentiation of HepaRG, a human bipotent progenitor cell, and discover that 3D microperfusion greatly enhances the hepatocyte differentiation efficiency over static 2D and 3D cultures. However, HepaRG progenitor cells are highly sensitive to the time-point at which microperfusion is applied. Isolated HepaRG cells that are primed as static 3D spheroids before being subjected to microperfusion yield a significantly higher proportion of HLCs (92%) than direct microperfusion of isolated HepaRG cells (62%). This platform potentially offers a simple and efficient means to develop highly functional microfluidic liver models incorporating human stem cell-derived HLCs. Biotechnol. Bioeng. 2017;114: 2360-2370. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. An efficient computer based wavelets approximation method to solve Fuzzy boundary value differential equations

    Science.gov (United States)

    Alam Khan, Najeeb; Razzaq, Oyoon Abdul

    2016-03-01

    In the present work a wavelets approximation method is employed to solve fuzzy boundary value differential equations (FBVDEs). Essentially, a truncated Legendre wavelets series together with the Legendre wavelets operational matrix of derivative are utilized to convert FB- VDE into a simple computational problem by reducing it into a system of fuzzy algebraic linear equations. The capability of scheme is investigated on second order FB- VDE considered under generalized H-differentiability. Solutions are represented graphically showing competency and accuracy of this method.

  6. Efficient Differentiation of Mouse Embryonic Stem Cells into Insulin-Producing Cells

    Directory of Open Access Journals (Sweden)

    Szu-Hsiu Liu

    2012-01-01

    Full Text Available Embryonic stem (ES cells are a potential source of a variety of differentiated cells for cell therapy, drug discovery, and toxicology screening. Here, we present an efficacy strategy for the differentiation of mouse ES cells into insulin-producing cells (IPCs by a two-step differentiation protocol comprising of (i the formation of definitive endoderm in monolayer culture by activin A, and (ii this monolayer endoderm being induced to differentiate into IPCs by nicotinamide, insulin, and laminin. Differentiated cells can be obtained within approximately 7 days. The differentiation IPCs combined application of RT-PCR, ELISA, and immunofluorescence to characterize phenotypic and functional properties. In our study, we demonstrated that IPCs produced pancreatic transcription factors, endocrine progenitor marker, definitive endoderm, pancreatic β-cell markers, and Langerhans α and δ cells. The IPCs released insulin in a manner that was dose dependent upon the amount of glucose added. These techniques may be able to be applied to human ES cells, which would have very important ramifications for treating human disease.

  7. Factor-Reduced Human Induced Pluripotent Stem Cells Efficiently Differentiate into Neurons Independent of the Number of Reprogramming Factors

    Directory of Open Access Journals (Sweden)

    Andreas Hermann

    2016-01-01

    Full Text Available Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs by overexpression of the transcription factors OCT4, SOX2, KLF4, and c-Myc holds great promise for the development of personalized cell replacement therapies. In an attempt to minimize the risk of chromosomal disruption and to simplify reprogramming, several studies demonstrated that a reduced set of reprogramming factors is sufficient to generate iPSC. We recently showed that a reduction of reprogramming factors in murine cells not only reduces reprogramming efficiency but also may worsen subsequent differentiation. To prove whether this is also true for human cells, we compared the efficiency of neuronal differentiation of iPSC generated from fetal human neural stem cells with either one (OCT4; hiPSC1F-NSC or two (OCT4, KLF4; hiPSC2F-NSC reprogramming factors with iPSC produced from human fibroblasts using three (hiPSC3F-FIB or four reprogramming factors (hiPSC4F-FIB. After four weeks of coculture with PA6 stromal cells, neuronal differentiation of hiPSC1F-NSC and hiPSC2F-NSC was as efficient as iPSC3F-FIB or iPSC4F-FIB. We conclude that a reduction of reprogramming factors in human cells does reduce reprogramming efficiency but does not alter subsequent differentiation into neural lineages. This is of importance for the development of future application of iPSC in cell replacement therapies.

  8. Efficient induction of dopaminergic neuron differentiation from induced pluripotent stem cells reveals impaired mitophagy in PARK2 neurons.

    Science.gov (United States)

    Suzuki, Sadafumi; Akamatsu, Wado; Kisa, Fumihiko; Sone, Takefumi; Ishikawa, Kei-Ichi; Kuzumaki, Naoko; Katayama, Hiroyuki; Miyawaki, Atsushi; Hattori, Nobutaka; Okano, Hideyuki

    2017-01-29

    Patient-specific induced pluripotent stem cells (iPSCs) show promise for use as tools for in vitro modeling of Parkinson's disease. We sought to improve the efficiency of dopaminergic (DA) neuron induction from iPSCs by the using surface markers expressed in DA progenitors to increase the significance of the phenotypic analysis. By sorting for a CD184 high /CD44 - fraction during neural differentiation, we obtained a population of cells that were enriched in DA neuron precursor cells and achieved higher differentiation efficiencies than those obtained through the same protocol without sorting. This high efficiency method of DA neuronal induction enabled reliable detection of reactive oxygen species (ROS) accumulation and vulnerable phenotypes in PARK2 iPSCs-derived DA neurons. We additionally established a quantitative system using the mt-mKeima reporter system to monitor mitophagy in which mitochondria fuse with lysosomes and, by combining this system with the method of DA neuronal induction described above, determined that mitophagy is impaired in PARK2 neurons. These findings suggest that the efficiency of DA neuron induction is important for the precise detection of cellular phenotypes in modeling Parkinson's disease. Copyright © 2016. Published by Elsevier Inc.

  9. Efficient design of FIR filter based low-pass differentiators for biomedical signal processing

    Directory of Open Access Journals (Sweden)

    Wulf Michael

    2016-09-01

    Full Text Available This paper describes an alternative design of linear phase low-pass differentiators with a finite impulse response (type III FIR filter. To reduce the number of necessary filter coefficients, the differentiator’s transfer function is approximated by a Fourier series of a triangle function. Thereby the filter’s transition steepness towards the stopband is intentionally reduced. It can be shown that the proposed design of low-pass differentiators yields to similar results as other published design recommendations, while the filter order can be significantly reduced.

  10. Manufacturing Employment and Wage Differentials After Structural Adjustment Reforms in Colombia: An Efficiency Wages Approach

    Directory of Open Access Journals (Sweden)

    Rodrigo Taborda

    2011-06-01

    Full Text Available In the framework of the structural reforms in Colombia one of the most important policy proposals was reducing rigidities in the labor market. A perspective to assess the results of such reforms is the analysis of the relationship between firm employment and wage differentials in manufacturing before and after the reforms. If the labor reforms reached the intended objective of making more flexible the labor market, the employment levels must change faster, along with the behavior of wages and other labor costs, given some characteristics of firms and the economy. This paper addresses this topic proposing a model of wage differential and employment growth and testing its propositions before and after the structural reforms and controlling for industry and firm characteristics. A first finding is the confirmation of the positive relationship proposed between intra-industry wage differential and employment. In the inter-industry wage differential estimation, we find heterogeneous responses depending on the industry and a reduction in the autonomous labor turnover.

  11. An Energy Efficient Hydraulic Winch Drive Concept Based on a Speed-variable Switched Differential Pump

    DEFF Research Database (Denmark)

    Schmidt, Lasse; Andersen, Torben O.; Pedersen, Henrik Clemmensen

    2017-01-01

    controls. Such solutions are typically constituted by many and rather expensive components, and are furthermore often suffering from low frequency dynamics. In this paper an alternative solution is proposed for winch drive operation, which is based on the so-called speed-variable switched differential pump......, originally designed for direct drive of hydraulic differential cylinders. This concept utilizes three pumps, driven by a single electric servo drive. The concept is redesigned for usage in winch drives, driven by flow symmetric hydraulic motors and single directional loads as commonly seen in e.g. active...... heave compensation applications. A general drive configuration approach is presented, along with a proper control strategy and design. The resulting concept is evaluated when applied for active heave compensation. Results demonstrate control performance on level with conventional valve solutions...

  12. Assessment of gender differentials in economic and technical efficiency of poultry egg, a case study in Lagos State, Nigeria.

    Directory of Open Access Journals (Sweden)

    Hafis Odunlami

    2016-03-01

    Full Text Available Gender has been seen as an important factor in the distribution and utilization of productive resources worldwide. In the agricultural sector, gender differential could influence the sourcing and efficient utilization of factors of production, particularly in the livestock sub-sector of the economy. This study assessed the gender differentials in economic and technical efficiency of poultry eggs production in Lagos State, Nigeria. Multistage sampling technique was used to select respondent poultry farmers. The first and second stages were the purposive selection of five Local Government Areas (LGAs reputed for poultry production and farm settlements in the state. The third stage involved a simple random sampling of 150 poultry farms consisting of 75 farms each managed by a male and a female Stochastic Frontier Analysis (SFA. The SFA revealed that for male management of poultry egg farms, labour input (p<0.01 and cost of medications (p<0.05 increased the poultry egg output. On the other hand, for female management, stock of birds (p<0.01, labour input (p<0.01 and feed cost (p<0.01 were the factors that increased poultry eggs output. The inefficiency model revealed that male farmers were more technically efficient (p<0.01 than female counterparts. Female managed poultry farms had less productivity (0.90 compared to males(1.22. However, 88.1% of male farms compared to 86.7% of female farms had economic efficiency ratios between 0.29 and 0.79. The study concluded that gender had impact on poultry farmers’ efficiency in the study area. The study therefore recommended that training should be organised for female managed farms while male managed farms should utilize less of cost intensive capital input.

  13. Highly Efficient Differentiation and Enrichment of Spinal Motor Neurons Derived from Human and Monkey Embryonic Stem Cells

    Science.gov (United States)

    Wada, Tamaki; Honda, Makoto; Minami, Itsunari; Tooi, Norie; Amagai, Yuji; Nakatsuji, Norio; Aiba, Kazuhiro

    2009-01-01

    Background There are no cures or efficacious treatments for severe motor neuron diseases. It is extremely difficult to obtain naïve spinal motor neurons (sMNs) from human tissues for research due to both technical and ethical reasons. Human embryonic stem cells (hESCs) are alternative sources. Several methods for MN differentiation have been reported. However, efficient production of naïve sMNs and culture cost were not taken into consideration in most of the methods. Methods/Principal Findings We aimed to establish protocols for efficient production and enrichment of sMNs derived from pluripotent stem cells. Nestin+ neural stem cell (NSC) clusters were induced by Noggin or a small molecule inhibitor of BMP signaling. After dissociation of NSC clusters, neurospheres were formed in a floating culture containing FGF2. The number of NSCs in neurospheres could be expanded more than 30-fold via several passages. More than 33% of HB9+ sMN progenitor cells were observed after differentiation of dissociated neurospheres by all-trans retinoic acid (ATRA) and a Shh agonist for another week on monolayer culture. HB9+ sMN progenitor cells were enriched by gradient centrifugation up to 80% purity. These HB9+ cells differentiated into electrophysiologically functional cells and formed synapses with myotubes during a few weeks after ATRA/SAG treatment. Conclusions and Significance The series of procedures we established here, namely neural induction, NSC expansion, sMN differentiation and sMN purification, can provide large quantities of naïve sMNs derived from human and monkey pluripotent stem cells. Using small molecule reagents, reduction of culture cost could be achieved. PMID:19701462

  14. Differential news framing of unmanned aerial drones: efficient and effective or illegal and inhumane?

    NARCIS (Netherlands)

    Sheets, P.; Rowling, C.; Jones, T.

    2012-01-01

    Over the past four years, the United States has significantly expanded its use of predator drones to conduct intelligence-gathering and military-strike operations. Experts are divided over this change in military strategy: some defend drones as a legal and efficient way to target terrorists, and

  15. Differentiability properties of the efficient (u,q2)-set in the Markowitz portfolio selection method

    NARCIS (Netherlands)

    Kriens, J.; Strijbosch, L.W.G.; Vörös, J.

    1994-01-01

    The set of efficient (Rho2)-combinations in the (Rho2)-plane of the Markowitz portfolio selection method consists of a series of strictly convex parabola. In the transition points from one parabola to the next one, the curve may be indifferentiable. The article gives necessary and sufficient

  16. Efficient Large-Scale 2D Culture System for Human Induced Pluripotent Stem Cells and Differentiated Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Shugo Tohyama

    2017-11-01

    Full Text Available Cardiac regenerative therapies utilizing human induced pluripotent stem cells (hiPSCs are hampered by ineffective large-scale culture. hiPSCs were cultured in multilayer culture plates (CPs with active gas ventilation (AGV, resulting in stable proliferation and pluripotency. Seeding of 1 × 106 hiPSCs per layer yielded 7.2 × 108 hiPSCs in 4-layer CPs and 1.7 × 109 hiPSCs in 10-layer CPs with pluripotency. hiPSCs were sequentially differentiated into cardiomyocytes (CMs in a two-dimensional (2D differentiation protocol. The efficiency of cardiac differentiation using 10-layer CPs with AGV was 66%–87%. Approximately 6.2–7.0 × 108 cells (4-layer and 1.5–2.8 × 109 cells (10-layer were obtained with AGV. After metabolic purification with glucose- and glutamine-depleted and lactate-supplemented media, a massive amount of purified CMs was prepared. Here, we present a scalable 2D culture system using multilayer CPs with AGV for hiPSC-derived CMs, which will facilitate clinical applications for severe heart failure in the near future.

  17. Tuning differentiation signals for efficient propagation and in vitro validation of rat embryonic stem cell cultures.

    Science.gov (United States)

    Meek, Stephen; Sutherland, Linda; Burdon, Tom

    2015-01-01

    The rat is one of the most commonly used laboratory animals in biomedical research and the recent isolation of genuine pluripotent rat embryonic stem (ES) cell lines has provided new opportunities for applying contemporary genetic engineering techniques to the rat and enhancing the use of this rodent in scientific research. Technical refinements that improve the stability of the rat ES cell cultures will undoubtedly further strengthen and broaden the use of these stem cells in biomedical research. Here, we describe a relatively simple and robust protocol that supports the propagation of germ line competent rat ES cells, and outline how tuning stem cell signaling using small molecule inhibitors can be used to both stabilize self-renewal of rat ES cell cultures and aid evaluation of their differentiation potential in vitro.

  18. An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Julia TCW

    2017-08-01

    Full Text Available Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs, via a neural progenitor cell (NPC intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals. Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity, and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our protocol is a reproducible, straightforward (single medium, and rapid (<30 days method to generate populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders.

  19. Differential cellulolytic activity of native-form and C-terminal tagged-form cellulase derived from coptotermes formosanus and expressed in E. coli

    Science.gov (United States)

    The endogenous cellulase gene (CfEG3a) of Coptotermes formosanus, an economically important pest termite, was cloned and overexpressed in both native form (nCfEG) and C-terminal His-tagged form (tCfEG) in E.coli. Both forms of recombinant cellulases showed hydrolytic activity on cellulosic substrate...

  20. Increased numbers of pre-existing memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells1

    Science.gov (United States)

    Joshi, Nikhil S.; Cui, Weiguo; Dominguez, Claudia; Chen, Jonathan H.; Hand, Timothy W.; Kaech, Susan M.

    2011-01-01

    Memory CD8 T cells acquire TEM properties following reinfection, and may reach terminally differentiated, senescent states (“Hayflick limit”) after multiple infections. The signals controlling this process are not well understood, but we found that the degree of 2o effector and memory CD8 T cell differentiation was intimately linked to the amount of T-bet expressed upon reactivation and pre-existing memory CD8 T cell number (i.e., 1o memory CD8 T cell precursor frequency) present during secondary infection. Compared to naïve cells, memory CD8 T cells were predisposed towards terminal effector (TE) cell differentiation because they could immediately respond to IL-12 and induce T-bet, even in the absence of antigen. TE cell formation following 2o or 3o infections was dependent on increased T-bet expression because T-bet+/− cells were resistant to these phenotypic changes. Larger numbers of pre-existing memory CD8 T cells limited the duration of 2o infection and the amount of IL-12 produced, and consequently, this reduced T-bet expression and the proportion of 2o TE CD8 T cells that formed. Together, these data show that, over repeated infections, memory CD8 T cell quality and proliferative fitness is not strictly determined by the number of serial encounters with antigen or cell divisions, but is a function of the CD8 T cell differentiation state, which is genetically controlled in a T-bet-dependent manner. This differentiation state can be modulated by pre-existing memory CD8 T cell number and the intensity of inflammation during reinfection. These results have important implications for vaccinations involving prime-boost strategies. PMID:21930973

  1. Following-up the efficiency of 131-Iodine therapy in differentiated thyroid carcinoma (excluding medullary) - Moroccan situation

    International Nuclear Information System (INIS)

    Ben Rais Aouad, N.

    2004-01-01

    Full text: Since 1985, the department of nuclear medicine of IBN SINA Hospital in the Rabat University hospital centre is the only centre in Morocco, where all patients of differentiated thyroid carcinoma after surgery are treated with 3.7 GBq of Iodine-131. The number of patients on follow-up is more than two thousands. The endemic zone represents the main origin of thyroid carcinoma. The sex ratio (F/M) is 3.5/1; the mean age is 42.5 years. The papillary carcinoma constitutes about 65.5% of the 26% of well-differentiated carcinoma and 12.5 of moderately differentiated carcinoma (MDC). The tumour size at diagnosis was more than 2 cm in 70% of cases. Prognosis factors are the age, the histology and tumour size. After the surgery, the patients receive 131-Iodine therapy (3.7 GBq) and a regular follow-up by clinical examination, neck ultrasonography and thyroglobulin (Tg) blood level. The aim is to obtain a negative whole body scan (WBS) and undetectable Tg. All the patients also receive a suppressive hormone therapy (thyroxin: 2.4 μg/kg/day). In the same patient, the Tg level is also compared with and without suppression therapy, but taking TSH levels into account. The efficiency of 131-Iodine treatment and the following up, depends on the type of patients: (a) Patients without metastasis: the success of Iodine-131 therapy depended on surgery and it was more than 92% (b) Patients with local metastasis to lymph nodes: the success of 131-Iodine therapy depended of nodal status and complete dissection is possible in 70% cases only. (c) Patients with distant metastasis: The efficiency of 131-Iodine therapy depended on the uptake, the homogeneity and the size of metastasis. In lung metastasis, the efficiency of 131-Iodine is about 40-42% (70%: miliary and micro nodules) and only 6.6% in bone metastasis. After treatment, the patients were regularly followed-up clinically till the next WBS and Tg estimation. In some cases, it was interesting to compare WBS and MIBI

  2. The adaptive CCCG({eta}) method for efficient solution of time dependent partial differential equations

    Energy Technology Data Exchange (ETDEWEB)

    Campos, F.F. [Universidade Federal de Minas Gerais, Belo Horizonte (Brazil); Birkett, N.R.C. [Oxford Univ. Computing Lab. (United Kingdom)

    1996-12-31

    The Controlled Cholesky factorisation has been shown to be a robust preconditioner for the Conjugate Gradient method. In this scheme the amount of fill-in is defined in terms of a parameter {eta}, the number of extra elements allowed per column. It is demonstrated how an optimum value of {eta} can be automatically determined when solving time dependent p.d.e.`s using an implicit time step method. A comparison between CCCG({eta}) and the standard ICCG solving parabolic problems on general grids shows CCCG({eta}) to be an efficient general purpose solver.

  3. Cytokine-free directed differentiation of human pluripotent stem cells efficiently produces hemogenic endothelium with lymphoid potential.

    Science.gov (United States)

    Galat, Yekaterina; Dambaeva, Svetlana; Elcheva, Irina; Khanolkar, Aaruni; Beaman, Kenneth; Iannaccone, Philip M; Galat, Vasiliy

    2017-03-17

    The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification. Thus, it has been shown that variations in cytokine and inhibitory molecule treatments in the first few days of hematopoietic differentiation define primitive versus definitive potential of produced hematopoietic progenitor cells. The majority of current feeder-free, defined systems for hematopoietic induction from pluripotent stem cells include prolonged incubations with various cytokines that make the differentiation process complex and time consuming. We established that the application of Wnt agonist CHIR99021 efficiently promotes differentiation of human pluripotent stem cells in the absence of any hematopoietic cytokines to the stage of hemogenic endothelium capable of definitive hematopoiesis. The hemogenic endothelium differentiation was accomplished in an adherent, serum-free culture system by applying CHIR99021. Hemogenic endothelium progenitor cells were isolated on day 5 of differentiation and evaluated for their endothelial, myeloid, and lymphoid potential. Monolayer induction based on GSK3 inhibition, described here, yielded a large number of CD31 + CD34 + hemogenic endothelium cells. When isolated and propagated in adherent conditions, these progenitors gave rise to mature endothelium. When further cocultured with OP9 mouse stromal cells, these progenitors gave rise to various cells of myeloid lineages as well as natural killer lymphoid, T

  4. Efficient Adjoint Computation of Hybrid Systems of Differential Algebraic Equations with Applications in Power Systems

    Energy Technology Data Exchange (ETDEWEB)

    Abhyankar, Shrirang [Argonne National Lab. (ANL), Argonne, IL (United States); Anitescu, Mihai [Argonne National Lab. (ANL), Argonne, IL (United States); Constantinescu, Emil [Argonne National Lab. (ANL), Argonne, IL (United States); Zhang, Hong [Argonne National Lab. (ANL), Argonne, IL (United States)

    2016-03-31

    Sensitivity analysis is an important tool to describe power system dynamic behavior in response to parameter variations. It is a central component in preventive and corrective control applications. The existing approaches for sensitivity calculations, namely, finite-difference and forward sensitivity analysis, require a computational effort that increases linearly with the number of sensitivity parameters. In this work, we investigate, implement, and test a discrete adjoint sensitivity approach whose computational effort is effectively independent of the number of sensitivity parameters. The proposed approach is highly efficient for calculating trajectory sensitivities of larger systems and is consistent, within machine precision, with the function whose sensitivity we are seeking. This is an essential feature for use in optimization applications. Moreover, our approach includes a consistent treatment of systems with switching, such as DC exciters, by deriving and implementing the adjoint jump conditions that arise from state and time-dependent discontinuities. The accuracy and the computational efficiency of the proposed approach are demonstrated in comparison with the forward sensitivity analysis approach.

  5. Determination of the state of operating mechanical stresses acting on surface piping with problems of differential collapses in the Venta de Carpio Terminal; Determinacion del estado de esfuerzos mecanicos actuantes en tuberias superficiales con problemas de hundimientos diferenciales en la Terminal Venta de Carpio

    Energy Technology Data Exchange (ETDEWEB)

    Neri B, Ernesto R; Garcia E, Nairoby [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico)

    2004-07-01

    The Venta de Carpio Terminal is located in the Northern part of the old Texcoco Lake, State of Mexico, in highly compressible soil. In it, it is received, regulated, measured and distributed natural gas, LP gas and PEMEX Refinacion products that are supplied to distribution terminals of and consumption centers located in the central area of the country, that encompasses the states of Puebla, Tlaxcala, Mexico, Hidalgo, Queretaro and a small part of the Federal District. The construction of the Venta de Carpio station dates from 1960; since then, it has presented important regional settlements, mainly due to the water extraction of the subsoil, that have imposed deformations to the piping systems connected to the surface facilities that have been piloted in the terminal. Equally, other surface piping systems and facilities present deformations by differential settlement between their supports. [Spanish] La Terminal Venta de Carpio se ubica en la parte norte del antiguo Lago de Texcoco, Estado de Mexico, en terreno altamente compresible. En ella, se recibe, regula, mide y distribuye gas natural, gas LP y productos de Pemex Refinacion que se suministran a terminales de distribucion y centros de consumo localizados en el area central del pais, que comprende los estados de Puebla, Tlaxcala, Mexico, Hidalgo, Queretaro y una pequena parte del Distrito Federal. La construccion de la estacion Venta de Carpio data de 1960; desde entonces, se han presentado asentamientos regionales importantes debidos, principalmente a la extraccion de agua del subsuelo, que han impuesto deformaciones a los sistemas de tuberias conectados con las instalaciones superficiales que han sido piloteadas en la terminal. De igual modo, otros sistemas de tuberias e instalaciones superficiales presentan deformaciones por hundimientos diferenciales entre sus apoyos.

  6. Efficient Generation of Human Embryonic Stem Cell-Derived Corneal Endothelial Cells by Directed Differentiation.

    Directory of Open Access Journals (Sweden)

    Kathryn L McCabe

    Full Text Available To generate human embryonic stem cell derived corneal endothelial cells (hESC-CECs for transplantation in patients with corneal endothelial dystrophies.Feeder-free hESC-CECs were generated by a directed differentiation protocol. hESC-CECs were characterized by morphology, expression of corneal endothelial markers, and microarray analysis of gene expression.hESC-CECs were nearly identical morphologically to primary human corneal endothelial cells, expressed Zona Occludens 1 (ZO-1 and Na+/K+ATPaseα1 (ATPA1 on the apical surface in monolayer culture, and produced the key proteins of Descemet's membrane, Collagen VIIIα1 and VIIIα2 (COL8A1 and 8A2. Quantitative PCR analysis revealed expression of all corneal endothelial pump transcripts. hESC-CECs were 96% similar to primary human adult CECs by microarray analysis.hESC-CECs are morphologically similar, express corneal endothelial cell markers and express a nearly identical complement of genes compared to human adult corneal endothelial cells. hESC-CECs may be a suitable alternative to donor-derived corneal endothelium.

  7. An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Tcw, Julia; Wang, Minghui; Pimenova, Anna A; Bowles, Kathryn R; Hartley, Brigham J; Lacin, Emre; Machlovi, Saima I; Abdelaal, Rawan; Karch, Celeste M; Phatnani, Hemali; Slesinger, Paul A; Zhang, Bin; Goate, Alison M; Brennand, Kristen J

    2017-08-08

    Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity, and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our protocol is a reproducible, straightforward (single medium), and rapid (method to generate populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Energy Efficient Clustering in Multi-hop Wireless Sensor Networks Using Differential Evolutionary MOPSO

    Directory of Open Access Journals (Sweden)

    D. Rajendra Prasad

    Full Text Available ABSTRACT The primary challenge in organizing sensor networks is energy efficacy. This requisite for energy efficacy is because sensor nodes capacities are limited and replacing them is not viable. This restriction further decreases network lifetime. Node lifetime varies depending on the requisites expected of its battery. Hence, primary element in constructing sensor networks is resilience to deal with decreasing lifetime of all sensor nodes. Various network infrastructures as well as their routing protocols for reduction of power utilization as well as to prolong network lifetime are studied. After analysis, it is observed that network constructions that depend on clustering are the most effective methods in terms of power utilization. Clustering divides networks into inter-related clusters such that every cluster has several sensor nodes with a Cluster Head (CH at its head. Sensor gathered information is transmitted to data processing centers through CH hierarchy in clustered environments. The current study utilizes Multi-Objective Particle Swarm Optimization (MOPSO-Differential Evolution (DE (MOPSO-DE technique for optimizing clustering.

  9. Collimated-hole structures as efficient differential pumping barrier, one-way valve and tool for aligning Penning traps

    International Nuclear Information System (INIS)

    Kluge, H.-Jürgen; Block, Michael; Herfurth, Frank

    2011-01-01

    A collimated-hole structure consists of a very large number of parallel channels which have each a very small diameter and are closely packed together. Such devices, installed in vacuum systems allow one to separate regions of very different gas pressures. A collimated-hole structure has high transmission for a directed ion beam with low emittance but a very low conductance for rest gas atoms or molecules exhibiting random walk. Therefore it is proposed to use such a structure as one-way valve and/or efficient differential pumping barrier in set-ups using Penning traps. Furthermore, these devices might be very useful to align the axis of a Penning trap with the direction of the magnetic field lines which is essential to avoid systematic uncertainties in high-accuracy mass spectroscopy.

  10. Efficient Multilevel and Multi-index Sampling Methods in Stochastic Differential Equations

    KAUST Repository

    Haji-Ali, Abdul Lateef

    2016-05-22

    Most problems in engineering and natural sciences involve parametric equations in which the parameters are not known exactly due to measurement errors, lack of measurement data, or even intrinsic variability. In such problems, one objective is to compute point or aggregate values, called “quantities of interest”. A rapidly growing research area that tries to tackle this problem is Uncertainty Quantification (UQ). As the name suggests, UQ aims to accurately quantify the uncertainty in quantities of interest. To that end, the approach followed in this thesis is to describe the parameters using probabilistic measures and then to employ probability theory to approximate the probabilistic information of the quantities of interest. In this approach, the parametric equations must be accurately solved for multiple values of the parameters to explore the dependence of the quantities of interest on these parameters, using various so-called “sampling methods”. In almost all cases, the parametric equations cannot be solved exactly and suitable numerical discretization methods are required. The high computational complexity of these numerical methods coupled with the fact that the parametric equations must be solved for multiple values of the parameters make UQ problems computationally intensive, particularly when the dimensionality of the underlying problem and/or the parameter space is high. This thesis is concerned with optimizing existing sampling methods and developing new ones. Starting with the Multilevel Monte Carlo (MLMC) estimator, we first prove its normality using the Lindeberg-Feller CLT theorem. We then design the Continuation Multilevel Monte Carlo (CMLMC) algorithm that efficiently approximates the parameters required to run MLMC. We also optimize the hierarchies of one-dimensional discretization parameters that are used in MLMC and analyze the tolerance splitting parameter between the statistical error and the bias constraints. An important contribution

  11. The efficiency of seismic attributes to differentiate between massive and non-massive carbonate successions for hydrocarbon exploration activity

    Science.gov (United States)

    Sarhan, Mohammad Abdelfattah

    2017-12-01

    The present work investigates the efficiency of applying volume seismic attributes to differentiate between massive and non-massive carbonate sedimentary successions on using seismic data. The main objective of this work is to provide a pre-drilling technique to recognize the porous carbonate section (probable hydrocarbon reservoirs) based on seismic data. A case study from the Upper Cretaceous - Eocene carbonate successions of Abu Gharadig Basin, northern Western Desert of Egypt has been tested in this work. The qualitative interpretations of the well-log data of four available wells distributed in the study area, namely; AG-2, AG-5, AG-6 and AG-15 wells, has confirmed that the Upper Cretaceous Khoman A Member represents the massive carbonate section whereas the Eocene Apollonia Formation represents the non-massive carbonate unit. The present work have proved that the most promising seismic attributes capable of differentiating between massive and non-massive carbonate sequences are; Root Mean Square (RMS) Amplitude, Envelope (Reflection Strength), Instantaneous Frequency, Chaos, Local Flatness and Relative Acoustic Impedance.

  12. Efficiency of B-mode Ultrasound and Strain Elastography in Differentiating Between Benign and Malignant Cervical Lymph Nodes.

    Science.gov (United States)

    Turgut, Eser; Celenk, Cetin; Tanrivermis Sayit, Asli; Bekci, Tumay; Gunbey, Hediye Pinar; Aslan, Kerim

    2017-09-01

    The purpose of this study was to evaluate the diagnostic accuracy and efficiency of ultrasonography (US), especially when combined with strain elastography (SE), in differentiating between benign and malignant cervical lymph nodes (LNs). Forty-one LNs were examined by B-mode US, power Doppler US, and SE. The following imaging features were analyzed: shape, echogenicity, echogenic hilum, calcification, intranodal vascular pattern, elasticity scores (5 categories), and strain ratio. The average strain ratio was calculated as the mean strain of the adjacent sternocleidomastoid muscle divided by the mean strain of the target LN. The results of the US and SE features were compared with the histopathologic findings. The imaging features that were significantly associated with malignant LNs were an increased short-to-long axis diameter ratio, abnormal or absence of hilum, microcalcification, type 2-3-4 vascularity, 3-4-5 elasticity scores, and a high level of strain ratio (P benign and malignant LNs. Strain elastography is useful in differentiating between benign and malignant cervical LNs, thereby informing decisions to perform a biopsy and/or surgery, and facilitating follow-up.

  13. Using Pd-salen complex as an efficient catalyst for the copper- and solvent-free coupling of acyl chlorides with terminal alkynes under aerobic conditions

    Institute of Scientific and Technical Information of China (English)

    Mohammad

    2010-01-01

    The palladium-salen complex palladium(Ⅱ) N,N'-bis{[5-(triphenylphosphonium)-methyl]salicylidene}-l,2-ethanediamine chloride was found to be a highly active catalyst for the copper- and solvent-free coupling reaction of terminal alkynes with different acyl chlorides in the presence of triethylamine as base, giving excellent ynones under aerobic conditions.

  14. Terminal Ballistics

    CERN Document Server

    Rosenberg, Zvi

    2012-01-01

    This book covers the important issues of terminal ballistics in a comprehensive way combining experimental data, numerical simulations and analytical modeling. The first chapter reviews the experimental equipment which are used for ballistic tests and the diagnostics for material characterization under impulsive loading conditions. The second chapter covers essential features of the codes which are used for terminal ballistics such as the Euler vs. Lagrange schemes and meshing techniques, as well as the most popular material models. The third chapter, devoted to the penetration mechanics of rigid penetrators, brings the update of modeling in this field. The fourth chapter deals with plate perforation and the fifth chapter deals with the penetration mechanics of shaped charge jets and eroding long rods. The last two chapters discuss several techniques for the disruption and defeating of the main threats in armor design. Throughout the book the authors demonstrate the advantages of numerical simulations in unde...

  15. Terminal structure

    Science.gov (United States)

    Schmidt, Frank [Langenhagen, DE; Allais, Arnaud [Hannover, DE; Mirebeau, Pierre [Villebon sur Yvette, FR; Ganhungu, Francois [Vieux-Reng, FR; Lallouet, Nicolas [Saint Martin Boulogne, FR

    2009-10-20

    A terminal structure (2) for a superconducting cable (1) is described. It consists of a conductor (2a) and an insulator (2b) that surrounds the conductor (2a), wherein the superconducting cable (1) has a core with a superconducting conductor (5) and a layer of insulation that surrounds the conductor (5), and wherein the core is arranged in such a way that it can move longitudinally in a cryostat. The conductor (2a) of the terminal structure (2) is electrically connected with the superconducting conductor (5) or with a normal conductor (6) that is connected with the superconducting conductor (5) by means of a tubular part (7) made of an electrically conductive material, wherein the superconducting conductor (5) or the normal conductor (6) can slide in the part (7) in the direction of the superconductor.

  16. Termination unit

    Energy Technology Data Exchange (ETDEWEB)

    Traeholt, Chresten; Willen, Dag; Roden, Mark; Tolbert, Jerry C.; Lindsay, David; Fisher, Paul W.; Nielsen, Carsten Thidemann

    2016-05-03

    Cable end section comprises end-parts of N electrical phases/neutral, and a thermally-insulation envelope comprising cooling fluid. The end-parts each comprises a conductor and are arranged with phase 1 innermost, N outermost surrounded by the neutral, electrical insulation being between phases and N and neutral. The end-parts comprise contacting surfaces located sequentially along the longitudinal extension of the end-section. A termination unit has an insulating envelope connected to a cryostat, special parts at both ends comprising an adapter piece at the cable interface and a closing end-piece terminating the envelope in the end-section. The special parts houses an inlet and/or outlet for cooling fluid. The space between an inner wall of the envelope and a central opening of the cable is filled with cooling fluid. The special part at the end connecting to the cryostat houses an inlet or outlet, splitting cooling flow into cable annular flow and termination annular flow.

  17. General and efficient one-pot synthesis of novel sugar/heterocyclic(aryl) 1,2-diketones from sugar terminal alkynes by Sonogashira/tetra-n- butylammonium permanganate oxidation.

    Science.gov (United States)

    Zhang, Fuyi; Wu, Xiaopei; Wang, Liming; Liu, Hong; Zhao, Yufen

    2015-11-19

    A new approach for one-pot synthesis of novel sugar/heterocyclic(aryl) 1,2-diketones has been achieved by the reaction of various sugar terminal alkynes with heterocyclic(aryl) iodides at room temperature. This one-pot protocol includes Sonogashira coupling and mild n-Bu4NMnO4 oxidation reaction. This method is mild, general and efficient. Fifty-six examples have been given and the sugar/heterocyclic(aryl) 1,2-diketones were obtained in 71-94% yields. The sugar terminal alkynes include 9 structurally different sugars in pyranose, furanose, and acyclic form which have various protecting groups, sensitive groups, and sterically bulky substituents. The heterocyclic(aryl) iodides include sterically bulky heterocyclic compounds and iodobenzenes with electron-donating, electron-neutral, and electron-withdrawing substituents. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Sonogashira Reaction of Aryl and Heteroaryl Halides with Terminal Alkynes Catalyzed by a Highly Efficient and Recyclable Nanosized MCM-41 Anchored Palladium Bipyridyl Complex

    Directory of Open Access Journals (Sweden)

    Chung-Yuan Mou

    2010-12-01

    Full Text Available A heterogeneous catalyst, nanosized MCM-41-Pd, was used to catalyze the Sonogashira coupling of aryl and heteroaryl halides with terminal alkynes in the presence of CuI and triphenylphosphine. The coupling products were obtained in high yields using low Pd loadings to 0.01 mol%, and the nanosized MCM-41-Pd catalyst was recovered by centrifugation of the reaction solution and re-used in further runs without significant loss of reactivity.

  19. A rapid and efficient synthetic route to terminal arylacetylenes by tetrabutylammonium hydroxide- and methanol-catalyzed cleavage of 4-aryl-2-methyl-3-butyn-2-ols

    Directory of Open Access Journals (Sweden)

    Pengcheng Huang

    2011-04-01

    Full Text Available Tetrabutylammonium hydroxide with methanol as an additive was found to be a highly active catalyst for the cleavage of 4-aryl-2-methyl-3-butyn-2-ols. The reaction was performed at 55–75 °C and gave terminal arylacetylenes in good to excellent yields within several minutes. Compared with the usual reaction conditions (normally >110 °C, several hours, this novel catalyst system can dramatically decrease the reaction time under much milder conditions.

  20. An Efficient and Practical Process for Pd/Cu Cocatalyzed Homocoupling Reaction of Terminal Alkynes Using Sodium Percarbonate as a Dual Reagent in Aqueous Media

    Institute of Scientific and Technical Information of China (English)

    ZHOU, Lei; ZHAN, Hai-Ying; LIU, Hai-Ling; JIANG, Huan-Feng

    2007-01-01

    A new process for the Pd/Cu co-catalyzed homocoupling reaction of terminal alkynes was developed. The reaction was carried out in aqueous media with sodium percarbonate as both a clean oxidant and a base. Meanwhile, a palladium complex immobilized on a synthetic PS-PEG400-PPh2 resin was used as the catalyst, which may be recovered by simple filtration and reused for several times with high activity.

  1. An efficient approach for differentiating Alzheimer's disease from normal elderly based on multicenter MRI using gray-level invariant features.

    Directory of Open Access Journals (Sweden)

    Muwei Li

    Full Text Available Machine learning techniques, along with imaging markers extracted from structural magnetic resonance images, have been shown to increase the accuracy to differentiate patients with Alzheimer's disease (AD from normal elderly controls. Several forms of anatomical features, such as cortical volume, shape, and thickness, have demonstrated discriminative capability. These approaches rely on accurate non-linear image transformation, which could invite several nuisance factors, such as dependency on transformation parameters and the degree of anatomical abnormality, and an unpredictable influence of residual registration errors. In this study, we tested a simple method to extract disease-related anatomical features, which is suitable for initial stratification of the heterogeneous patient populations often encountered in clinical data. The method employed gray-level invariant features, which were extracted from linearly transformed images, to characterize AD-specific anatomical features. The intensity information from a disease-specific spatial masking, which was linearly registered to each patient, was used to capture the anatomical features. We implemented a two-step feature selection for anatomic recognition. First, a statistic-based feature selection was implemented to extract AD-related anatomical features while excluding non-significant features. Then, seven knowledge-based ROIs were used to capture the local discriminative powers of selected voxels within areas that were sensitive to AD or mild cognitive impairment (MCI. The discriminative capability of the proposed feature was measured by its performance in differentiating AD or MCI from normal elderly controls (NC using a support vector machine. The statistic-based feature selection, together with the knowledge-based masks, provided a promising solution for capturing anatomical features of the brain efficiently. For the analysis of clinical populations, which are inherently heterogeneous

  2. Chapter 10: Peak Demand and Time-Differentiated Energy Savings Cross-Cutting Protocol. The Uniform Methods Project: Methods for Determining Energy Efficiency Savings for Specific Measures

    Energy Technology Data Exchange (ETDEWEB)

    Kurnik, Charles W [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Stern, Frank [Navigant, Boulder, CO (United States); Spencer, Justin [Navigant, Boulder, CO (United States)

    2017-10-03

    Savings from electric energy efficiency measures and programs are often expressed in terms of annual energy and presented as kilowatt-hours per year (kWh/year). However, for a full assessment of the value of these savings, it is usually necessary to consider the measure or program's impact on peak demand as well as time-differentiated energy savings. This cross-cutting protocol describes methods for estimating the peak demand and time-differentiated energy impacts of measures implemented through energy efficiency programs.

  3. Analysis of the differentially expressed low molecular weight peptides in human serum via an N-terminal isotope labeling technique combining nano-liquid chromatography/matrix-assisted laser desorption/ionization mass spectrometry.

    Science.gov (United States)

    Leng, Jiapeng; Zhu, Dong; Wu, Duojiao; Zhu, Tongyu; Zhao, Ningwei; Guo, Yinlong

    2012-11-15

    Peptidomics analysis of human serum is challenging due to the low abundance of serum peptides and interference from the complex matrix. This study analyzed the differentially expressed (DE) low molecular weight peptides in human serum integrating a DMPITC-based N-terminal isotope labeling technique with nano-liquid chromatography and matrix-assisted laser desorption/ionization mass spectrometry (nano-LC/MALDI-MS). The workflow introduced a [d(6)]-4,6-dimethoxypyrimidine-2-isothiocyanate (DMPITC)-labeled mixture of aliquots from test samples as the internal standard. The spiked [d(0)]-DMPITC-labeled samples were separated by nano-LC then spotted on the MALDI target. Both quantitative and qualitative studies for serum peptides were achieved based on the isotope-labeled peaks. The DMPITC labeling technique combined with nano-LC/MALDI-MS not only minimized the errors in peptide quantitation, but also allowed convenient recognition of the labeled peptides due to the 6 Da mass difference. The data showed that the entire research procedure as well as the subsequent data analysis method were effective, reproducible, and sensitive for the analysis of DE serum peptides. This study successfully established a research model for DE serum peptides using DMPITC-based N-terminal isotope labeling and nano-LC/MALDI-MS. Application of the DMPITC-based N-terminal labeling technique is expected to provide a promising tool for the investigation of peptides in vivo, especially for the analysis of DE peptides under different biological conditions. Copyright © 2012 John Wiley & Sons, Ltd.

  4. An efficient reconstruction algorithm for differential phase-contrast tomographic images from a limited number of views

    International Nuclear Information System (INIS)

    Sunaguchi, Naoki; Yuasa, Tetsuya; Gupta, Rajiv; Ando, Masami

    2015-01-01

    The main focus of this paper is reconstruction of tomographic phase-contrast image from a set of projections. We propose an efficient reconstruction algorithm for differential phase-contrast computed tomography that can considerably reduce the number of projections required for reconstruction. The key result underlying this research is a projection theorem that states that the second derivative of the projection set is linearly related to the Laplacian of the tomographic image. The proposed algorithm first reconstructs the Laplacian image of the phase-shift distribution from the second-derivative of the projections using total variation regularization. The second step is to obtain the phase-shift distribution by solving a Poisson equation whose source is the Laplacian image previously reconstructed under the Dirichlet condition. We demonstrate the efficacy of this algorithm using both synthetically generated simulation data and projection data acquired experimentally at a synchrotron. The experimental phase data were acquired from a human coronary artery specimen using dark-field-imaging optics pioneered by our group. Our results demonstrate that the proposed algorithm can reduce the number of projections to approximately 33% as compared with the conventional filtered backprojection method, without any detrimental effect on the image quality

  5. Genes encoded within 8q24 on the amplicon of a large extrachromosomal element are selectively repressed during the terminal differentiation of HL-60 cells

    OpenAIRE

    Hirano, Tetsuo; Ike, Fumio; Murata, Takehide; Obata, Yuichi; Utiyama, Hiroyasu; Yokoyama, Kazunari K.

    2008-01-01

    Human acute myeloblastic leukemia HL-60 cells become resistant to differentiation during long­term cultivation. After 150 passages, double minute chromosomes (dmins) found in early­-passaged cells are replaced by large extrachromosomal elements (LEEs). In a DNA library derived from a purified fraction of LEEs, 12.6% (23/183) of clones were assigned to 8q24 and 9.2% (17/183) were assigned to 14q11 in the human genome. Fluorescence in situ hybridization (FISH) revealed a small aberrant chromos...

  6. Efficient Near-Infrared-Transparent Perovskite Solar Cells Enabling Direct Comparison of 4-Terminal and Monolithic Perovskite/Silicon Tandem Cells

    OpenAIRE

    Werner, Jérémie; Barraud, Loris; Walter, Arnaud; Bräuninger, Matthias; Sahli, Florent; Sacchetto, Davide; Tétreault, Nicolas; Paviet-Salomon, Bertrand; Moon, Soo-Jin; Allebé, Christophe; Despeisse, Matthieu; Nicolay, Sylvain; De Wolf, Stefaan; Niesen, Bjoern; Ballif, Christophe

    2016-01-01

    Combining market-proven silicon solar cell technology with an efficient wide band gap top cell into a tandem device is an attractive approach to reduce the cost of photovoltaic systems. For this, perovskite solar cells are promising high-efficiency top cell candidates, but their typical device size (

  7. Role of N-terminal His6-Tags in binding and efficient translocation of polypeptides into cells using anthrax protective antigen (PA.

    Directory of Open Access Journals (Sweden)

    Christoph Beitzinger

    Full Text Available It is of interest to define bacterial toxin biochemical properties to use them as molecular-syringe devices in order to deliver enzymatic activities into host cells. Binary toxins of the AB(7/8-type are among the most potent and specialized bacterial protein toxins. The B subunits oligomerize to form a pore that binds with high affinity host cell receptors and the enzymatic A subunit. This allows the endocytosis of the complex and subsequent injection of the A subunit into the cytosol of the host cells. Here we report that the addition of an N-terminal His(6-tag to different proteins increased their binding affinity to the protective antigen (PA PA(63-channels, irrespective if they are related (C2I or unrelated (gpJ, EDIN to the AB(7/8-family of toxins. His(6-EDIN exhibited voltage-dependent increase of the stability constant for binding by a factor of about 25 when the trans-side corresponding to the cell interior was set to -70 mV. Surprisingly, the C. botulinum toxin C2II-channel did not share this feature of PA(63. Cell-based experiments demonstrated that addition of an N-terminal His(6-tag promoted also intoxication of endothelial cells by C2I or EDIN via PA(63. Our results revealed that addition of His(6-tags to several factors increase their binding properties to PA(63 and enhance the property to intoxicate cells.

  8. Terminal ballistics

    CERN Document Server

    Rosenberg, Zvi

    2016-01-01

    This book comprehensively discusses essential aspects of terminal ballistics, combining experimental data, numerical simulations and analytical modeling. Employing a unique approach to numerical simulations as a measure of sensitivity for the major physical parameters, the new edition also includes the following features: new figures to better illustrate the problems discussed; improved explanations for the equation of state of a solid and for the cavity expansion process; new data concerning the Kolsky bar test; and a discussion of analytical modeling for the hole diameter in a thin metallic plate impacted by a shaped charge jet. The section on thick concrete targets penetrated by rigid projectiles has now been expanded to include the latest findings, and two new sections have been added: one on a novel approach to the perforation of thin concrete slabs, and one on testing the failure of thin metallic plates using a hydrodynamic ram.

  9. Ctr9, a Key Component of the Paf1 Complex, Affects Proliferation and Terminal Differentiation in the Developing Drosophila Nervous System

    Directory of Open Access Journals (Sweden)

    Shahrzad Bahrampour

    2016-10-01

    Full Text Available The Paf1 protein complex (Paf1C is increasingly recognized as a highly conserved and broadly utilized regulator of a variety of transcriptional processes. These include the promotion of H3K4 and H3K36 trimethylation, H2BK123 ubiquitination, RNA Pol II transcriptional termination, and also RNA-mediated gene silencing. Paf1C contains five canonical protein components, including Paf1 and Ctr9, which are critical for overall complex integrity, as well as Rtf1, Leo1, and Cdc73/Parafibromin(Hrpt2/Hyrax. In spite of a growing appreciation for the importance of Paf1C from yeast and mammalian studies, there has only been limited work in Drosophila. Here, we provide the first detailed phenotypic study of Ctr9 function in Drosophila. We found that Ctr9 mutants die at late embryogenesis or early larval life, but can be partly rescued by nervous system reexpression of Ctr9. We observed a number of phenotypes in Ctr9 mutants, including increased neuroblast numbers, increased nervous system proliferation, as well as downregulation of many neuropeptide genes. Analysis of cell cycle and regulatory gene expression revealed upregulation of the E2f1 cell cycle factor, as well as changes in Antennapedia and Grainy head expression. We also found reduction of H3K4me3 modification in the embryonic nervous system. Genome-wide transcriptome analysis points to additional downstream genes that may underlie these Ctr9 phenotypes, revealing gene expression changes in Notch pathway target genes, cell cycle genes, and neuropeptide genes. In addition, we find significant effects on the gene expression of metabolic genes. These findings reveal that Ctr9 is an essential gene that is necessary at multiple stages of nervous system development, and provides a starting point for future studies of the Paf1C in Drosophila.

  10. A Hybrid One-Way ANOVA Approach for the Robust and Efficient Estimation of Differential Gene Expression with Multiple Patterns.

    Directory of Open Access Journals (Sweden)

    Mohammad Manir Hossain Mollah

    Full Text Available Identifying genes that are differentially expressed (DE between two or more conditions with multiple patterns of expression is one of the primary objectives of gene expression data analysis. Several statistical approaches, including one-way analysis of variance (ANOVA, are used to identify DE genes. However, most of these methods provide misleading results for two or more conditions with multiple patterns of expression in the presence of outlying genes. In this paper, an attempt is made to develop a hybrid one-way ANOVA approach that unifies the robustness and efficiency of estimation using the minimum β-divergence method to overcome some problems that arise in the existing robust methods for both small- and large-sample cases with multiple patterns of expression.The proposed method relies on a β-weight function, which produces values between 0 and 1. The β-weight function with β = 0.2 is used as a measure of outlier detection. It assigns smaller weights (≥ 0 to outlying expressions and larger weights (≤ 1 to typical expressions. The distribution of the β-weights is used to calculate the cut-off point, which is compared to the observed β-weight of an expression to determine whether that gene expression is an outlier. This weight function plays a key role in unifying the robustness and efficiency of estimation in one-way ANOVA.Analyses of simulated gene expression profiles revealed that all eight methods (ANOVA, SAM, LIMMA, EBarrays, eLNN, KW, robust BetaEB and proposed perform almost identically for m = 2 conditions in the absence of outliers. However, the robust BetaEB method and the proposed method exhibited considerably better performance than the other six methods in the presence of outliers. In this case, the BetaEB method exhibited slightly better performance than the proposed method for the small-sample cases, but the the proposed method exhibited much better performance than the BetaEB method for both the small- and large

  11. Comparative transcriptome analysis of nodules of two Mesorhizobium-chickpea associations with differential symbiotic efficiency under phosphate deficiency.

    Science.gov (United States)

    Nasr Esfahani, Maryam; Inoue, Komaki; Chu, Ha Duc; Nguyen, Kien Huu; Van Ha, Chien; Watanabe, Yasuko; Burritt, David J; Herrera-Estrella, Luis; Mochida, Keiichi; Tran, Lam-Son Phan

    2017-09-01

    Phosphate (Pi) deficiency is known to be a major limitation for symbiotic nitrogen fixation (SNF), and hence legume crop productivity globally. However, very little information is available on the adaptive mechanisms, particularly in the important legume crop chickpea (Cicer arietinum L.), which enable nodules to respond to low-Pi availability. Thus, to elucidate these mechanisms in chickpea nodules at molecular level, we used an RNA sequencing approach to investigate transcriptomes of the nodules in Mesorhizobium mediterraneum SWRI9-(MmSWRI9)-chickpea and M. ciceri CP-31-(McCP-31)-chickpea associations under Pi-sufficient and Pi-deficient conditions, of which the McCP-31-chickpea association has a better SNF capacity than the MmSWRI9-chickpea association during Pi starvation. Our investigation revealed that more genes showed altered expression patterns in MmSWRI9-induced nodules than in McCP-31-induced nodules (540 vs. 225) under Pi deficiency, suggesting that the Pi-starvation-more-sensitive MmSWRI9-induced nodules required expression change in a larger number of genes to cope with low-Pi stress than the Pi-starvation-less-sensitive McCP-31-induced nodules. The functional classification of differentially expressed genes (DEGs) was examined to gain an understanding of how chickpea nodules respond to Pi starvation, caused by soil Pi deficiency. As a result, more DEGs involved in nodulation, detoxification, nutrient/ion transport, transcriptional factors, key metabolic pathways, Pi remobilization and signalling were found in Pi-starved MmSWRI9-induced nodules than in Pi-starved McCP-31-induced nodules. Our findings have enabled the identification of molecular processes that play important roles in the acclimation of nodules to Pi deficiency, ultimately leading to the development of Pi-efficient chickpea symbiotic associations suitable for Pi-deficient soils. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  12. Honey bee venom combined with 1,25-dihydroxyvitamin D3as a highly efficient inducer of differentiation in human acute myeloid leukemia cells.

    Science.gov (United States)

    Mohseni-Kouchesfahani, Homa; Nabioni, Mohammad; Khosravi, Zahra; Rahimi, Maryam

    2017-01-01

    Most cancer cells exhibit a defect in their capacity to mature into nonreplicating adult cells and existing in a highly proliferating state. Differentiation therapy by agents such as 1,25-dihydroxyvitamin D3(1,25-(OH)2 VD3) represents a useful approach for the treatment of cancer including acute myeloid leukemia. Human myeloid leukemia cell lines are induced to terminal differentiation into monocyte lineage by 1,25-(OH)2 VD3. However, usage of these findings in the clinical trials is limited by calcemic effects of 1,25-(OH)2 VD3. Attempts to overcome this problem have focused on a combination of low concentrations 1,25-(OH)2 VD3 with other compounds to induce differentiation of HL-60 cells. In this study, the effect of honey bee venom (BV) and 1,25-(OH)2 VD3, individually and in combination, on proliferation and differentiation of human myeloid leukemia HL-60 cells were assayed. In this in vitro study, toxic and nontoxic concentrations of BV and 1,25-(OH)2 VD3 were tested using Trypan blue stained cell counting and (3[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. In addition, differentiation of cells was assayed using a Wright-Giemsa staining and nitroblue tetrazolium reduction test. Data were analyzed by a one-way analysis of the variance test using SPSS software. Our findings showed that both the BV and 1,25-(OH)2 VD3, in a dose and time-dependent manner, caused cell death at high concentrations and inhibited cell proliferation at lower concentrations. About 5 nM of 1,25-(OH)2 VD3 induced differentiation of HL-60 cells to monocytes after 72 h. 2.5 μg/ml of BV suppressed proliferation of HL-60 cells but had not any effects on their differentiation, whereas in combination with 5 nM of 1,25-(OH)2 VD3, it enhanced antiproliferative and differentiation potency of 1,25-(OH)2 VD3. These results indicate that BV potentiates the 1,25-(OH)2 VD3-induced HL-60 cell differentiation into monocytes.

  13. Termination unit

    Science.gov (United States)

    Traeholt, Chresten [Frederiksberg, DK; Willen, Dag [Klagshamn, SE; Roden, Mark [Newnan, GA; Tolbert, Jerry C [Carrollton, GA; Lindsay, David [Carrollton, GA; Fisher, Paul W [Heiskell, TN; Nielsen, Carsten Thidemann [Jaegerspris, DK

    2014-01-07

    This invention relates to a termination unit comprising an end-section of a cable. The end section of the cable defines a central longitudinal axis and comprising end-parts of N electrical phases, an end-part of a neutral conductor and a surrounding thermally insulation envelope adapted to comprising a cooling fluid. The end-parts of the N electrical phases and the end-part of the neutral conductor each comprising at least one electrical conductor and being arranged in the cable concentrically around a core former with a phase 1 located relatively innermost, and phase N relatively outermost in the cable, phase N being surrounded by the neutral conductor, electrical insulation being arrange between neighboring electrical phases and between phase N and the neutral conductor, and wherein the end-parts of the neutral conductor and the electrical phases each comprise a contacting surface electrically connected to at least one branch current lead to provide an electrical connection: The contacting surfaces each having a longitudinal extension, and being located sequentially along the longitudinal extension of the end-section of the cable. The branch current leads being individually insulated from said thermally insulation envelope by individual electrical insulators.

  14. Efficient farnesylation of an extended C-terminal C(x)3X sequence motif expands the scope of the prenylated proteome.

    Science.gov (United States)

    Blanden, Melanie J; Suazo, Kiall F; Hildebrandt, Emily R; Hardgrove, Daniel S; Patel, Meet; Saunders, William P; Distefano, Mark D; Schmidt, Walter K; Hougland, James L

    2018-02-23

    Protein prenylation is a post-translational modification that has been most commonly associated with enabling protein trafficking to and interaction with cellular membranes. In this process, an isoprenoid group is attached to a cysteine near the C terminus of a substrate protein by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase type I or II (GGTase-I and GGTase-II). FTase and GGTase-I have long been proposed to specifically recognize a four-amino acid C AAX C-terminal sequence within their substrates. Surprisingly, genetic screening reveals that yeast FTase can modify sequences longer than the canonical C AAX sequence, specifically C( x ) 3 X sequences with four amino acids downstream of the cysteine. Biochemical and cell-based studies using both peptide and protein substrates reveal that mammalian FTase orthologs can also prenylate C( x ) 3 X sequences. As the search to identify physiologically relevant C( x ) 3 X proteins begins, this new prenylation motif nearly doubles the number of proteins within the yeast and human proteomes that can be explored as potential FTase substrates. This work expands our understanding of prenylation's impact within the proteome, establishes the biologically relevant reactivity possible with this new motif, and opens new frontiers in determining the impact of non-canonically prenylated proteins on cell function. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Vitamin E isomer δ-tocopherol enhances the efficiency of neural stem cell differentiation via L-type calcium channel.

    Science.gov (United States)

    Deng, Sihao; Hou, Guoqiang; Xue, Zhiqin; Zhang, Longmei; Zhou, Yuye; Liu, Chao; Liu, Yanqing; Li, Zhiyuan

    2015-01-12

    The effects of the vitamin E isomer δ-tocopherol on neural stem cell (NSC) differentiation have not been investigated until now. Here we investigated the effects of δ-tocopherol on NSC neural differentiation, maturation and its possible mechanisms. Neonatal rat NSCs were grown in suspended neurosphere cultures, and were identified by their expression of nestin protein and their capacity for self-renewal. Treatment with a low concentration of δ-tocopherol induced a significant increase in the percentage of β-III-tubulin-positive cells. δ-Tocopherol also stimulated morphological maturation of neurons in culture. We further observed that δ-tocopherol stimulation increased the expression of voltage-dependent Ca(2+) channels. Moreover, a L-type specific Ca(2+) channel blocker verapamil reduced the percentage of differentiated neurons after δ-tocopherol treatment, and blocked the effects of δ-tocopherol on NSC differentiation into neurons. Together, our study demonstrates that δ-tocopherol may act through elevation of L-type calcium channel activity to increase neuronal differentiation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Managing magnetic nanoparticle aggregation and cellular uptake: a precondition for efficient stem-cell differentiation and MRI tracking.

    Science.gov (United States)

    Fayol, Delphine; Luciani, Nathalie; Lartigue, Lenaic; Gazeau, Florence; Wilhelm, Claire

    2013-02-01

    The labeling of stem cells with iron oxide nanoparticles is increasingly used to enable MRI cell tracking and magnetic cell manipulation, stimulating the fields of tissue engineering and cell therapy. However, the impact of magnetic labeling on stem-cell differentiation is still controversial. One compromising factor for successful differentiation may arise from early interactions of nanoparticles with cells during the labeling procedure. It is hypothesized that the lack of control over nanoparticle colloidal stability in biological media may lead to undesirable nanoparticle localization, overestimation of cellular uptake, misleading MRI cell tracking, and further impairment of differentiation. Herein a method is described for labeling mesenchymal stem cells (MSC), in which the physical state of citrate-coated nanoparticles (dispersed versus aggregated) can be kinetically tuned through electrostatic and magnetic triggers, as monitored by diffusion light scattering in the extracellular medium and by optical and electronic microscopy in cells. A set of statistical cell-by-cell measurements (flow cytometry, single-cell magnetophoresis, and high-resolution MRI cellular detection) is used to independently quantify the nanoparticle cell uptake and the effects of nanoparticle aggregation. Such aggregation confounds MRI cell detection as well as global iron quantification and has adverse effects on chondrogenetic differentiation. Magnetic labeling conditions with perfectly stable nanoparticles-suitable for obtaining differentiation-capable magnetic stem cells for use in cell therapy-are subsequently identified. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Concept Layout Model of Transportation Terminals

    OpenAIRE

    Yao, Li-ya; Sun, Li-shan; Wang, Wu-hong; Xiong, Hui

    2012-01-01

    Transportation terminal is the key node in transport systems. Efficient terminals can improve operation of passenger transportation networks, adjust the layout of public transportation networks, provide a passenger guidance system, and regulate the development of commercial forms, as well as optimize the assembly and distribution of modern logistic modes, among others. This study aims to clarify the relationship between the function and the structure of transportation terminals and establish ...

  18. Efficient transfection of Xenobiotic Responsive Element-biosensor plasmid using diether lipid and phosphatidylcholine liposomes in differentiated HepaRG cells.

    Science.gov (United States)

    Demazeau, Maxime; Quesnot, Nicolas; Ripoche, Nicolas; Rauch, Claudine; Jeftić, Jelena; Morel, Fabrice; Gauffre, Fabienne; Benvegnu, Thierry; Loyer, Pascal

    2017-05-30

    In this study, we evaluated cationic liposomes prepared from diether-NH 2 and egg phosphatidylcholine (EPC) for in vitro gene delivery. The impact of the lipid composition, i.e. the EPC and Diether-NH 2 molar ratio, on in vitro transfection efficiency and cytotoxicity was investigated using the human HEK293T and hepatoma HepaRG cells known to be permissive and poorly permissive cells for liposome-mediated gene transfer, respectively. Here, we report that EPC/Diether-NH 2 -based liposomes enabled a very efficient transfection with low cytotoxicity compared to commercial transfection reagents in both HEK293T and proliferating progenitor HepaRG cells. Taking advantage of these non-toxic EPC/Diether-NH 2 -based liposomes, we developed a method to efficiently transfect differentiated hepatocyte-like HepaRG cells and a biosensor plasmid containing a Xenobiotic Responsive Element and a minimal promoter driving the transcription of the luciferase reporter gene. We demonstrated that the luciferase activity was induced by a canonical inducer of cytochrome P450 genes, the benzo[a]pyrene, and two environmental contaminants, the fluoranthene, a polycyclic aromatic hydrocarbon, and the endosulfan, an organochlorine insecticide, known to induce toxicity and genotoxicity in differentiated HepaRG cells. In conclusion, we established a new efficient lipofection-mediated gene transfer in hepatocyte-like HepaRG cells opening new perspectives in drug evaluation relying on xenobiotic inducible biosensor plasmids. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Technical efficiency and productivity differentials of dairy farms in three EU countries: the role of CAP subsidies

    NARCIS (Netherlands)

    Xueqin Zhu, Xueqin; Demeter, R.M.; Oude Lansink, A.G.J.M.

    2012-01-01

    The impact of EU agricultural support policies on farms’ economic performance is an interesting issue for policy makers. The objective of this paper is to investigate technical efficiency and technical efficiency change of specialized German, Dutch and Swedish dairy farms and to compare their

  20. Improved hematopoietic differentiation efficiency of gene-corrected beta-thalassemia induced pluripotent stem cells by CRISPR/Cas9 system.

    Science.gov (United States)

    Song, Bing; Fan, Yong; He, Wenyin; Zhu, Detu; Niu, Xiaohua; Wang, Ding; Ou, Zhanhui; Luo, Min; Sun, Xiaofang

    2015-05-01

    The generation of beta-thalassemia (β-Thal) patient-specific induced pluripotent stem cells (iPSCs), subsequent homologous recombination-based gene correction of disease-causing mutations/deletions in the β-globin gene (HBB), and their derived hematopoietic stem cell (HSC) transplantation offers an ideal therapeutic solution for treating this disease. However, the hematopoietic differentiation efficiency of gene-corrected β-Thal iPSCs has not been well evaluated in the previous studies. In this study, we used the latest gene-editing tool, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9), to correct β-Thal iPSCs; gene-corrected cells exhibit normal karyotypes and full pluripotency as human embryonic stem cells (hESCs) showed no off-targeting effects. Then, we evaluated the differentiation efficiency of the gene-corrected β-Thal iPSCs. We found that during hematopoietic differentiation, gene-corrected β-Thal iPSCs showed an increased embryoid body ratio and various hematopoietic progenitor cell percentages. More importantly, the gene-corrected β-Thal iPSC lines restored HBB expression and reduced reactive oxygen species production compared with the uncorrected group. Our study suggested that hematopoietic differentiation efficiency of β-Thal iPSCs was greatly improved once corrected by the CRISPR/Cas9 system, and the information gained from our study would greatly promote the clinical application of β-Thal iPSC-derived HSCs in transplantation.

  1. Nucleotide excision repair in differentiated cells

    Energy Technology Data Exchange (ETDEWEB)

    Wees, Caroline van der [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Jansen, Jacob [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Vrieling, Harry [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Laarse, Arnoud van der [Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Zeeland, Albert van [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Mullenders, Leon [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands)]. E-mail: l.mullenders@lumc.nl

    2007-01-03

    Nucleotide excision repair (NER) is the principal pathway for the removal of a wide range of DNA helix-distorting lesions and operates via two NER subpathways, i.e. global genome repair (GGR) and transcription-coupled repair (TCR). Although detailed information is available on expression and efficiency of NER in established mammalian cell lines, little is known about the expression of NER pathways in (terminally) differentiated cells. The majority of studies in differentiated cells have focused on repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4-photoproducts (6-4PP) because of the high frequency of photolesions at low level of toxicity and availability of sensitive technologies to determine photolesions in defined regions of the genome. The picture that emerges from these studies is blurred and rather complex. Fibroblasts and terminally differentiated myocytes of the rat heart display equally efficient GGR of 6-4PP but poor repair of CPD due to the absence of p48 expression. This repair phenotype is clearly different from human terminal differentiated neurons. Furthermore, both cell types were found to carry out TCR of CPD, thus mimicking the repair phenotype of established rodent cell lines. In contrast, in intact rat spermatogenic cells repair was very inefficient at the genome overall level and in transcriptionally active genes indicating that GGR and TCR are non-functional. Also, non-differentiated mouse embryonic stem (ES) cells exhibit low levels of NER after UV irradiation. However, the mechanisms that lead to low NER activity are clearly different: in differentiated spermatogenic cells differences in chromatin compaction and sequestering of NER proteins may underlie the lack of NER activity in pre-meiotic cells, whereas in non-differentiated ES cells NER is impaired by a strong apoptotic response.

  2. Energy efficient and fast reversal of a fixed skyrmion two-terminal memory with spin current assisted by voltage controlled magnetic anisotropy

    Science.gov (United States)

    Bhattacharya, Dhritiman; Mamun Al-Rashid, Md; Atulasimha, Jayasimha

    2017-10-01

    Recent work (P-H Jang et al 2015 Appl. Phys. Lett. 107 202401, J. Sampaio et al 2016 Appl. Phys. Lett. 108 112403) suggests that ferromagnetic reversal with spin transfer torque (STT) requires more current in a system in the presence of Dzyaloshinskii-Moriya interaction (DMI) than switching a typical ferromagnet of the same dimensions and perpendicular magnetic anisotropy (PMA). However, DMI promotes the stabilization of skyrmions and we report that when perpendicular anisotropy is modulated (reduced) for both the skyrmion and ferromagnet, it takes a much smaller current to reverse the fixed skyrmion than to reverse the ferromagnet in the same amount of time, or the skyrmion reverses much faster than the ferromagnet at similar levels of current. We show with rigorous micromagnetic simulations that skyrmion switching proceeds along a different path at very low PMA, which results in a significant reduction in the spin current or time required for reversal. This can offer potential for memory applications where a relatively simple modification of the standard STT-RAM (to include a heavy metal adjacent to the soft magnetic layer and with appropriate design of the tunnel barrier) can lead to an energy efficient and fast magnetic memory device based on the reversal of fixed skyrmions.

  3. Differential mode EMI filter design for ultra high efficiency partial parallel isolated full-bridge boost converter

    DEFF Research Database (Denmark)

    Makda, Ishtiyaq Ahmed; Nymand, M.

    2013-01-01

    for such application, it calls for a carefully optimized EMI filter which is designed and implemented in this work. Moreover, the negative input impedance of the regulated converter is extremely low; well-designed filter damping branch is also included. Differential mode noise is analyzed analytically for a 3KW/400V...

  4. Closed-channel culture system for efficient and reproducible differentiation of human pluripotent stem cells into islet cells

    International Nuclear Information System (INIS)

    Hirano, Kunio; Konagaya, Shuhei; Turner, Alexander; Noda, Yuichiro; Kitamura, Shigeru; Kotera, Hidetoshi; Iwata, Hiroo

    2017-01-01

    Human pluripotent stem cells (hPSCs) are thought to be a promising cell-source solution for regenerative medicine due to their indefinite proliferative potential and ability to differentiate to functional somatic cells. However, issues remain with regard to achieving reproducible differentiation of cells with the required functionality for realizing human transplantation therapies and with regard to reducing the potential for bacterial or fungal contamination. To meet these needs, we have developed a closed-channel culture device and corresponding control system. Uniformly-sized spheroidal hPSCs aggregates were formed inside wells within a closed-channel and maintained continuously throughout the culture process. Functional islet-like endocrine cell aggregates were reproducibly induced following a 30-day differentiation protocol. Our system shows an easily scalable, novel method for inducing PSC differentiation with both purity and functionality. - Highlights: • A simple, closed-channel-based, semi-automatic culture system is proposed. • Uniform cell aggregate formation and culture is realized in microwell structure. • Functional islet cells are successfully induced following 30-plus-day protocol. • System requires no daily medium replacement and reduces contamination risk.

  5. The strontium inorganic mutant of the water oxidizing center (CaMn4O5) of PSII improves WOC efficiency but slows electron flux through the terminal acceptors.

    Science.gov (United States)

    Gates, Colin; Ananyev, Gennady; Dismukes, G Charles

    2016-09-01

    Herein we extend prior studies of biosynthetic strontium replacement of calcium in PSII-WOC core particles to characterize whole cells. Previous studies of Thermosynechococcus elongatus found a lower rate of light-saturated O2 from isolated PSII-WOC(Sr) cores and 5-8× slower rate of oxygen release. We find similar properties in whole cells, and show it is due to a 20% larger Arrhenius activation barrier for O2 evolution. Cellular adaptation to the sluggish PSII-WOC(Sr) cycle occurs in which flux through the QAQB acceptor gate becomes limiting for turnover rate in vivo. Benzoquinone derivatives that bind to QB site remove this kinetic chokepoint yielding 31% greater O2 quantum yield (QY) of PSII-WOC(Sr) vs. PSII-WOC(Ca). QY and efficiency of the WOC(Sr) catalytic cycle are greatly improved at low light flux, due to fewer misses and backward transitions and 3-fold longer lifetime of the unstable S3 state, attributed to greater thermodynamic stabilization of the WOC(Sr) relative to the photoactive tyrosine YZ. More linear and less cyclic electron flow through PSII occurs per PSII-WOC(Sr). The organismal response to the more active PSII centers in Sr-grown cells at 45°C is to lower the number of active PSII-WOC per Chl, producing comparable oxygen and energy per cell. We conclude that redox and protonic energy fluxes created by PSII are primary determinants for optimal growth rate of T. elongatus. We further conclude that the (Sr-favored) intermediate-spin S=5/2 form of the S2 state is the active form in the catalytic cycle relative to the low-spin S=1/2 form. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Robust and highly-efficient differentiation of functional monocytic cells from human pluripotent stem cells under serum- and feeder cell-free conditions.

    Directory of Open Access Journals (Sweden)

    Masakatsu D Yanagimachi

    Full Text Available Monocytic lineage cells (monocytes, macrophages and dendritic cells play important roles in immune responses and are involved in various pathological conditions. The development of monocytic cells from human embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs is of particular interest because it provides an unlimited cell source for clinical application and basic research on disease pathology. Although the methods for monocytic cell differentiation from ESCs/iPSCs using embryonic body or feeder co-culture systems have already been established, these methods depend on the use of xenogeneic materials and, therefore, have a relatively poor-reproducibility. Here, we established a robust and highly-efficient method to differentiate functional monocytic cells from ESCs/iPSCs under serum- and feeder cell-free conditions. This method produced 1.3 × 10(6 ± 0.3 × 10(6 floating monocytes from approximately 30 clusters of ESCs/iPSCs 5-6 times per course of differentiation. Such monocytes could be differentiated into functional macrophages and dendritic cells. This method should be useful for regenerative medicine, disease-specific iPSC studies and drug discovery.

  7. Efficient production of native lunasin with correct N-terminal processing by using the pH-induced self-cleavable Ssp DnaB mini-intein system in Escherichia coli.

    Science.gov (United States)

    Setrerrahmane, Sarra; Zhang, Yi; Dai, Guangzhi; Lv, Jing; Tan, Shuhua

    2014-09-01

    To develop an efficient and cost-effective approach for the production of small preventive peptide lunasin with correct natural N terminus, a synthetic gene was designed by OPTIMIZER & Gene Designer and cloned into pTWIN1 vector at SapI and PstI sites. Thus, lunasin was N-terminally fused to the pH-induced self-cleavable Ssp DnaB mini-intein linked to a chitin binding domain (CBD) with no extra residues. The resultant fusion protein was highly expressed by lactose induction in Escherichia coli BL21 (DE3) in a 7-l bioreactor and bound to a chitin affinity column. After washing the impurities, the Ssp DnaB intein mediated on-column self-cleavage was easily triggered by shifting pH and temperature to allow the native lunasin released. The final purified lunasin yielded up to 75 mg/l medium. Tricine/SDS-PAGE and matrix-assisted laser desorption time-of-flight (MALDI-TOF)/mass spectrometry (MS) verified the structural authenticity of the product, implying the correct cleavage at the junction between Ssp DnaB intein and lunasin. MTT assay confirmed its potent proliferation inhibitory activity to human cancer cells HCT-116 and MDA-MB-231; however, no cytotoxicity to normal human lens epithelial cell SRA01/04 and hepatoma HepG2. Taken together, we provide a novel strategy to produce recombinant native lunasin with correct N-terminal processing by using the pH-induced self-cleavable Ssp DnaB mini-intein.

  8. Efficient and Fast Differentiation of Human Neural Stem Cells from Human Embryonic Stem Cells for Cell Therapy

    Directory of Open Access Journals (Sweden)

    Xinxin Han

    2017-01-01

    Full Text Available Stem cell-based therapies have been used for repairing damaged brain tissue and helping functional recovery after brain injury. Aberrance neurogenesis is related with brain injury, and multipotential neural stem cells from human embryonic stem (hES cells provide a great promise for cell replacement therapies. Optimized protocols for neural differentiation are necessary to produce functional human neural stem cells (hNSCs for cell therapy. However, the qualified procedure is scarce and detailed features of hNSCs originated from hES cells are still unclear. In this study, we developed a method to obtain hNSCs from hES cells, by which we could harvest abundant hNSCs in a relatively short time. Then, we examined the expression of pluripotent and multipotent marker genes through immunostaining and confirmed differentiation potential of the differentiated hNSCs. Furthermore, we analyzed the mitotic activity of these hNSCs. In this report, we provided comprehensive features of hNSCs and delivered the knowledge about how to obtain more high-quality hNSCs from hES cells which may help to accelerate the NSC-based therapies in brain injury treatment.

  9. HiDi: an efficient reverse engineering schema for large-scale dynamic regulatory network reconstruction using adaptive differentiation.

    Science.gov (United States)

    Deng, Yue; Zenil, Hector; Tegnér, Jesper; Kiani, Narsis A

    2017-12-15

    The use of differential equations (ODE) is one of the most promising approaches to network inference. The success of ODE-based approaches has, however, been limited, due to the difficulty in estimating parameters and by their lack of scalability. Here, we introduce a novel method and pipeline to reverse engineer gene regulatory networks from gene expression of time series and perturbation data based upon an improvement on the calculation scheme of the derivatives and a pre-filtration step to reduce the number of possible links. The method introduces a linear differential equation model with adaptive numerical differentiation that is scalable to extremely large regulatory networks. We demonstrate the ability of this method to outperform current state-of-the-art methods applied to experimental and synthetic data using test data from the DREAM4 and DREAM5 challenges. Our method displays greater accuracy and scalability. We benchmark the performance of the pipeline with respect to dataset size and levels of noise. We show that the computation time is linear over various network sizes. The Matlab code of the HiDi implementation is available at: www.complexitycalculator.com/HiDiScript.zip. hzenilc@gmail.com or narsis.kiani@ki.se. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  10. HiDi: an efficient reverse engineering schema for large-scale dynamic regulatory network reconstruction using adaptive differentiation

    KAUST Repository

    Deng, Yue

    2017-08-05

    Motivation: The use of differential equations (ODE) is one of the most promising approaches to network inference. The success of ODE-based approaches has, however, been limited, due to the difficulty in estimating parameters and by their lack of scalability. Here, we introduce a novel method and pipeline to reverse engineer gene regulatory networks from gene expression of time series and perturbation data based upon an improvement on the calculation scheme of the derivatives and a pre-filtration step to reduce the number of possible links. The method introduces a linear differential equation model with adaptive numerical differentiation that is scalable to extremely large regulatory networks. Results: We demonstrate the ability of this method to outperform current state-of-the-art methods applied to experimental and synthetic data using test data from the DREAM4 and DREAM5 challenges. Our method displays greater accuracy and scalability. We benchmark the performance of the pipeline with respect to dataset size and levels of noise. We show that the computation time is linear over various network sizes.

  11. Performance Evaluation and Modelling of Container Terminals

    Science.gov (United States)

    Venkatasubbaiah, K.; Rao, K. Narayana; Rao, M. Malleswara; Challa, Suresh

    2018-02-01

    The present paper evaluates and analyzes the performance of 28 container terminals of south East Asia through data envelopment analysis (DEA), principal component analysis (PCA) and hybrid method of DEA-PCA. DEA technique is utilized to identify efficient decision making unit (DMU)s and to rank DMUs in a peer appraisal mode. PCA is a multivariate statistical method to evaluate the performance of container terminals. In hybrid method, DEA is integrated with PCA to arrive the ranking of container terminals. Based on the composite ranking, performance modelling and optimization of container terminals is carried out through response surface methodology (RSM).

  12. Assessment of a bedside test for N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac causes of pleural effusion in cats.

    Science.gov (United States)

    Wurtinger, Gabriel; Henrich, Estelle; Hildebrandt, Nicolai; Wiedemann, Nicola; Schneider, Matthias; Hassdenteufel, Esther

    2017-12-20

    Cats with pleural effusion represent common emergencies in small animal practice. The aim of this prospective study was to investigate the diagnostic ability of a point-of-care ELISA (POC-ELISA) for the measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac disease in cats with pleural effusion. The sample material for use of this rapid test was either plasma or diluted pleural effusion. Twenty cats with moderate to severe pleural effusion were prospectively recruited. The cats were grouped into two groups, with or without congestive heart failure (CHF; N-CHF), after complete work-up. Blood and effusion were collected in EDTA tubes. Plasma and pleural effusion supernatants were transferred into stabilizer tubes and frozen. POC-ELISA for NT-proBNP was performed with plasma and diluted effusion (1:1). Quantitative NT-proBNP measurement was performed in plasma and diluted and undiluted effusions. Six cats were assigned to the CHF group. Of the 14 cats in the N-CHF group, 6 had concurrent cardiac abnormalities that were not responsible for the effusion. For the detection of CHF, the test displayed respective sensitivities and specificities of 100% and 79% in plasma and 100% and 86% in diluted pleural fluid. Receiver operating characteristic (ROC) analysis for quantitative NT-proBNP measurement of plasma and diluted and undiluted pleural effusions displayed areas under the curve of 0.98, sensitivities of 100% and specificities of 86%. The optimum cut-off was calculated at 399 pmol/l in plasma and 229 pmol/l in the diluted effusion and 467 pmol/l in the undiluted effusion. POC-ELISA for NT-proBNP in both plasma and diluted pleural effusion was suitable to differentiate cardiac from non-cardiac causes of feline pleural effusion. According to our results, use of pleural effusion is feasible, but dilution of the effusion before measurement seems to improve specificity.

  13. Design and simulations of a spectral efficient optical code division multiple access scheme using alternated energy differentiation and single-user soft-decision demodulation

    Science.gov (United States)

    A. Garba, Aminata

    2017-01-01

    This paper presents a new approach to optical Code Division Multiple Access (CDMA) network transmission scheme using alternated amplitude sequences and energy differentiation at the transmitters to allow concurrent and secure transmission of several signals. The proposed system uses error control encoding and soft-decision demodulation to reduce the multi-user interference at the receivers. The design of the proposed alternated amplitude sequences, the OCDMA energy modulators and the soft decision, single-user demodulators are also presented. Simulation results show that the proposed scheme allows achieving spectral efficiencies higher than several reported results for optical CDMA and much higher than the Gaussian CDMA capacity limit.

  14. Validation of mobile eye tracking as novel and efficient means for differentiating progressive supranuclear palsy from Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Svenja eMarx

    2012-12-01

    Full Text Available Background: The decreased ability to carry out vertical saccades is a key symptom of Progressive Supranuclear Palsy (PSP. Objective measurement devices can help to reliably detect subtle eye-movement disturbances to improve sensitivity and specificity of the clinical diagnosis. The present study aims at transferring findings from restricted stationary video-oculography to a wearable head-mounted device, which can be readily applied in clinical practice.Methods: We investigated the eye movements in 10 possible or probable PSP patients, 11 Parkinson’s disease (PD patients and 10 age-matched healthy controls (HC using a mobile, gaze-driven video camera setup (EyeSeeCam. Ocular movements were analyzed during a standardized fixation protocol and in an unrestricted real-life scenario while walking along a corridor.Results: The EyeSeeCam detected prominent impairment of both saccade velocity and amplitude in PSP patients, differentiating them from PD and HCs. Differences were particularly evident for saccades in the vertical plane, and stronger for saccades than for other eye movements. Differences were more pronounced during the standardized protocol than in the real-life scenario. Conclusions: Combined analysis of saccade velocity and saccade amplitude during the fixation protocol with the EyeSeeCam provides a simple, rapid (< 20s and reliable tool to differentiate clinically established PSP patients from PD and HCs. As such, our findings prepare the ground for using wearable eye-tracking in patients with uncertain diagnoses.

  15. Rapid and efficient CRISPR/Cas9 gene inactivation in human neurons during human pluripotent stem cell differentiation and direct reprogramming.

    Science.gov (United States)

    Rubio, Alicia; Luoni, Mirko; Giannelli, Serena G; Radice, Isabella; Iannielli, Angelo; Cancellieri, Cinzia; Di Berardino, Claudia; Regalia, Giulia; Lazzari, Giovanna; Menegon, Andrea; Taverna, Stefano; Broccoli, Vania

    2016-11-18

    The CRISPR/Cas9 system is a rapid and customizable tool for gene editing in mammalian cells. In particular, this approach has widely opened new opportunities for genetic studies in neurological disease. Human neurons can be differentiated in vitro from hPSC (human Pluripotent Stem Cells), hNPCs (human Neural Precursor Cells) or even directly reprogrammed from fibroblasts. Here, we described a new platform which enables, rapid and efficient CRISPR/Cas9-mediated genome targeting simultaneously with three different paradigms for in vitro generation of neurons. This system was employed to inactivate two genes associated with neurological disorder (TSC2 and KCNQ2) and achieved up to 85% efficiency of gene targeting in the differentiated cells. In particular, we devised a protocol that, combining the expression of the CRISPR components with neurogenic factors, generated functional human neurons highly enriched for the desired genome modification in only 5 weeks. This new approach is easy, fast and that does not require the generation of stable isogenic clones, practice that is time consuming and for some genes not feasible.

  16. kosh Terminal Aerodrome Forecast

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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  15. Organizational Relationship Termination Competence

    DEFF Research Database (Denmark)

    Ritter, Thomas; Geersbro, Jens

    2011-01-01

    termination are found to significantly affect a firm's relationship termination competence. The findings suggest that managers should regard termination as a legitimate option in customer relationship management. In order to decrease the number of unwanted customers, managers must accept termination......Most firms are involved in a number of customer relationships that drain the firm's resources. However, many firms are hesitant to address this problem. This paper investigates customer relationship termination at the organizational level. We develop and analyze the organizational dimensions...... of organizational termination in order to improve our understanding of the management of termination. The impact of these termination dimensions on the percentage of unwanted customers is developed and tested using PLS on data gathered from a cross-sectional survey of more than 800 sales representatives. We find...

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    Data.gov (United States)

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  1. kpit Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  2. kcrw Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  3. paen Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  4. kast Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  5. kuin Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  6. kmht Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  7. kcys Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  8. kflo Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  9. pakn Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  10. pabt Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  11. krdg Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  12. khdn Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  13. kjac Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  14. kphx Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  15. Highly efficient reprogramming to pluripotency and directed differentiation of human cells using synthetic modified mRNA

    OpenAIRE

    Warren, Luigi; Manos, Philip D.; Ahfeldt, Tim; Loh, Yuin-Han; Li, Hu; Lau, Frank; Ebina, Wataru; Mandal, Pankaj; Smith, Zachary D.; Meissner, Alexander; Daley, George Q.; Brack, Andrew S.; Collins, James J.; Cowan, Chad; Schlaeger, Thorsten M.

    2010-01-01

    Clinical application of induced pluripotent stem (iPS) cells is limited by the low efficiency of iPS derivation and the fact that most protocols modify the genome to effect cellular reprogramming. Moreover, safe and effective means of directing the fate of patient-specific iPS cells towards clinically useful cell types are lacking. Here we describe a simple, non-integrating strategy for reprogramming cell fate based on administration of synthetic mRNA modified to overcome innate anti-viral re...

  16. 42 CFR 421.205 - Termination by the Secretary.

    Science.gov (United States)

    2010-10-01

    ... for termination. The Secretary may terminate a contract with a carrier at any time if he or she... performed its function in a manner inconsistent with the effective and efficient administration of the... intent to terminate the contract, the carrier may request a hearing within 20 days after the date on the...

  17. Differential transfection efficiency rates of the GM-CSF gene into human renal cell carcinoma lines by lipofection.

    Science.gov (United States)

    Hernández, A; Zöller, K; Enczmann, J; Ebert, T; Schmitz-Draeger, B; Ackermann, R; Wernet, P

    1997-01-01

    One of the major questions in any gene therapy approach is the selection of the appropriate vector system. Here, the optimization of a gene transfer protocol for renal cell carcinoma using lipofection as a nonviral gene transduction system was evaluated. To select the promoter which gives the highest expression, different plasmids which are able to express Escherichia coli beta-galactosidase gene as a reporter gene under the control of different promoters were tested: human cytomegalovirus promoter (pCMVbeta), simian virus 40 promoter (pSVbeta), adenovirus promoter (ADbeta), and herpes simplex virus thymidine kinase promoter (TKbeta). The pCMVbeta revealed the highest expression of the beta-gal gene in the renal cell carcinoma (RCC) lines. Thus this CMV promoter was selected for the expression of the granulocyte-macrophage colony stimulator factor (GM-CSF) gene. Three different lipids (LipofectAmine, LipofectAce, and Lipofectin) were compared for their transduction efficiency, and the optimal conditions for quantitatively high lipofection rates were established. The consistently best results regarding gene expression as well as viability of the RCC lines were obtained when Lipofectin was used. Gene expression was monitored by a specific enzyme-linked immunosorbent assay and functionally validated by a cell proliferation test. The GM-CSF expression profile showed a peak at 48 hours after transfection and was still detectable after 5 days. Here the feasibility of efficient lipofection of the GM-CSF gene into RCC lines is demonstrated. Most importantly, considerable differences in the relative quantity of GM-CSF gene transfer into the different RCC lines was observed here. This may be of critical relevance for the design of any clinical gene transduction protocol in tumor cell vaccination attempts.

  18. A 45.8fJ/Step, energy-efficient, differential SAR capacitance-to-digital converter for capacitive pressure sensing

    KAUST Repository

    Alhoshany, Abdulaziz

    2016-05-03

    An energy-efficient readout circuit for a capacitive sensor is presented. The capacitive sensor is digitized by a 12-bit energy efficient capacitance-to-digital converter (CDC) that is based on a differential successive-approximation architecture. This CDC meets extremely low power requirements by using an operational transconductance amplifier (OTA) that is based on a current-starved inverter. It uses a charge-redistribution DAC that involves coarse-fine architecture. We split the DAC into a coarse-DAC and a fine-DAC to allow a wide capacitance range in a compact area. It covers a wide range of capacitance of 16.14 pF with a 4.5 fF absolute resolution. An analog comparator is implemented by cross-coupling two 3-input NAND gates to enable power and area efficient operation. The prototype CDC was fabricated using a standard 180 nm CMOS technology. The 12-bit CDC has a measurement time of 42.5 μs, and consumes 3.54 μW and 0.29 μW from analog and digital supplies, respectively. This corresponds to a state-of-the-art figure-of-merit (FoM) of 45.8 fJ/conversion-step. © 2016 Elsevier B.V. All rights reserved.

  19. A 45.8fJ/Step, energy-efficient, differential SAR capacitance-to-digital converter for capacitive pressure sensing

    KAUST Repository

    Alhoshany, Abdulaziz; Omran, Hesham; Salama, Khaled N.

    2016-01-01

    An energy-efficient readout circuit for a capacitive sensor is presented. The capacitive sensor is digitized by a 12-bit energy efficient capacitance-to-digital converter (CDC) that is based on a differential successive-approximation architecture. This CDC meets extremely low power requirements by using an operational transconductance amplifier (OTA) that is based on a current-starved inverter. It uses a charge-redistribution DAC that involves coarse-fine architecture. We split the DAC into a coarse-DAC and a fine-DAC to allow a wide capacitance range in a compact area. It covers a wide range of capacitance of 16.14 pF with a 4.5 fF absolute resolution. An analog comparator is implemented by cross-coupling two 3-input NAND gates to enable power and area efficient operation. The prototype CDC was fabricated using a standard 180 nm CMOS technology. The 12-bit CDC has a measurement time of 42.5 μs, and consumes 3.54 μW and 0.29 μW from analog and digital supplies, respectively. This corresponds to a state-of-the-art figure-of-merit (FoM) of 45.8 fJ/conversion-step. © 2016 Elsevier B.V. All rights reserved.

  20. Real-Time Dispatching of Rubber Tired Gantry Cranes in Container Terminals

    National Research Council Canada - National Science Library

    McNary, Bradley S

    2008-01-01

    ... significant growth in container traffic. Efficiently managing of rubber tired gantry cranes and planning container placement within the terminal are two ways to increase the overall efficiency of a terminal...

  1. Clustering based gene expression feature selection method: A computational approach to enrich the classifier efficiency of differentially expressed genes

    KAUST Repository

    Abusamra, Heba

    2016-07-20

    The native nature of high dimension low sample size of gene expression data make the classification task more challenging. Therefore, feature (gene) selection become an apparent need. Selecting a meaningful and relevant genes for classifier not only decrease the computational time and cost, but also improve the classification performance. Among different approaches of feature selection methods, however most of them suffer from several problems such as lack of robustness, validation issues etc. Here, we present a new feature selection technique that takes advantage of clustering both samples and genes. Materials and methods We used leukemia gene expression dataset [1]. The effectiveness of the selected features were evaluated by four different classification methods; support vector machines, k-nearest neighbor, random forest, and linear discriminate analysis. The method evaluate the importance and relevance of each gene cluster by summing the expression level for each gene belongs to this cluster. The gene cluster consider important, if it satisfies conditions depend on thresholds and percentage otherwise eliminated. Results Initial analysis identified 7120 differentially expressed genes of leukemia (Fig. 15a), after applying our feature selection methodology we end up with specific 1117 genes discriminating two classes of leukemia (Fig. 15b). Further applying the same method with more stringent higher positive and lower negative threshold condition, number reduced to 58 genes have be tested to evaluate the effectiveness of the method (Fig. 15c). The results of the four classification methods are summarized in Table 11. Conclusions The feature selection method gave good results with minimum classification error. Our heat-map result shows distinct pattern of refines genes discriminating between two classes of leukemia.

  2. Skeletal Muscle Differentiation on a Chip Shows Human Donor Mesoangioblasts' Efficiency in Restoring Dystrophin in a Duchenne Muscular Dystrophy Model.

    Science.gov (United States)

    Serena, Elena; Zatti, Susi; Zoso, Alice; Lo Verso, Francesca; Tedesco, F Saverio; Cossu, Giulio; Elvassore, Nicola

    2016-12-01

    : Restoration of the protein dystrophin on muscle membrane is the goal of many research lines aimed at curing Duchenne muscular dystrophy (DMD). Results of ongoing preclinical and clinical trials suggest that partial restoration of dystrophin might be sufficient to significantly reduce muscle damage. Different myogenic progenitors are candidates for cell therapy of muscular dystrophies, but only satellite cells and pericytes have already entered clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from DMD patients, using a microengineered model. We designed an ad hoc experimental strategy to miniaturize on a chip the standard process of muscle regeneration independent of variables such as inflammation and fibrosis. It is based on the coculture, at different ratios, of human dystrophin-positive myogenic progenitors and dystrophin-negative myoblasts in a substrate with muscle-like physiological stiffness and cell micropatterns. Results showed that both healthy myoblasts and mesoangioblasts restored dystrophin expression in DMD myotubes. However, mesoangioblasts showed unexpected efficiency with respect to myoblasts in dystrophin production in terms of the amount of protein produced (40% vs. 15%) and length of the dystrophin membrane domain (210-240 µm vs. 40-70 µm). These results show that our microscaled in vitro model of human DMD skeletal muscle validated previous in vivo preclinical work and may be used to predict efficacy of new methods aimed at enhancing dystrophin accumulation and distribution before they are tested in vivo, reducing time, costs, and variability of clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of human mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from

  3. Efficient Differentiation of Mycobacterium tuberculosis Strains of the W-Beijing Family from Russia using Highly Polymorphic VNTR Loci

    International Nuclear Information System (INIS)

    Surikova, O. V.; Voitech, D. S.; Kuzmicheva, G.; Tatkov, S. I.; Mokrousov, I. V.; Narvskaya, O. V.; Rot, M. A.; Soolingen, D. van; Filipenko, M. L.

    2005-01-01

    The W-Beijing family is a widespread Mycobacterium tuberculosis clonal lineage that frequently causes epidemic outbreaks. This family is genetically homogeneous and conserved, so ETR-VNTR (exact tandem repeat-variable number of tandem repeats) typing is insufficient for strain differentiation, due to a common ETR-A to E profile (42435). This leads to the false clustering in molecular epidemiological studies, especially in the regions of predominance of the W-Beijing family. In this study, we searched for VNTR loci with a high evolutionary rate of polymorphism in the W-Beijing genome. Here we further evaluated VNTR typing on a set of 99 Mycobacterium tuberculosis clinical isolates and reference strains. These isolates were characterized and classified into several genotype families based on three ETR loci (A, C, E) and eight additional loci [previously described as QUB (Queen's University Belfast) or MIRU (Mycobacterial Interspersed Repetitive Units) or Mtubs]. Ninety-nine strains were divided into 74 VNTR-types, 51 isolates of the W-Beijing family identified by IS6110 RFLP-typing (the restriction fragment length polymorphism-typing) and/or spoligotyping were subdivided into 30 VNTR-types. HGDI (the Hunter-Gaston discriminatory index) for all studied loci was close to that of IS6110 RFLP typing, a 'gold standard' method for subtyping M. tuberculosis complex strains. The QUB 26 and QUB 18 loci located in the PPE genes were highly polymorphic and more discriminative than other loci (HGDI is 0.8). Statistically significant increase of tandem repeats number in loci ETR-A, -E, QUB 26, QUB 18, QUB 11B, Mtub21 was revealed in the W-Beijing group compared to genetically divergent non-W-Beijing strains. Thirty-six isolates were subjected to IS6110 RFLP typing. The congruence between results of the IS6110 RFLP typing and 11-loci VNTR typing was estimated on 23 isolates of the W-Beijing family. These isolates were subdivided into 9 IS6110-RFLP types and 13 VNTR types. The poor

  4. Three-Terminal Amorphous Silicon Solar Cells

    Directory of Open Access Journals (Sweden)

    Cheng-Hung Tai

    2011-01-01

    Full Text Available Many defects exist within amorphous silicon since it is not crystalline. This provides recombination centers, thus reducing the efficiency of a typical a-Si solar cell. A new structure is presented in this paper: a three-terminal a-Si solar cell. The new back-to-back p-i-n/n-i-p structure increased the average electric field in a solar cell. A typical a-Si p-i-n solar cell was also simulated for comparison using the same thickness and material parameters. The 0.28 μm-thick three-terminal a-Si solar cell achieved an efficiency of 11.4%, while the efficiency of a typical a-Si p-i-n solar cell was 9.0%. Furthermore, an efficiency of 11.7% was achieved by thickness optimization of the three-terminal solar cell.

  5. Differential antioxidative responses in transgenic peanut bear no relationship to their superior transpiration efficiency under drought stress.

    Science.gov (United States)

    Bhatnagar-Mathur, Pooja; Devi, M Jyostna; Vadez, Vincent; Sharma, Kiran K

    2009-07-15

    To counter the effects of environmental stresses, the plants must undergo detoxification that is crucial to avoid the accumulation of damaging free oxygen radicals (ROI). Here, we detail the oxidative damage, the antioxidant composition, and the osmoprotection achieved in transgenic plants of peanut overexpressing the AtDREB1A transgene, driven by a stress-inducible promoter (Atrd29A) when exposed to progressive water stress conditions. This study explored the biochemical mechanisms where (i) the antioxidants such as superoxide dismutase (SOD), ascorbate peroxidase (APOX), and glutathione reductase (GR) accumulated in the transgenic plants at comparably higher levels than their untransformed counterparts under dry soil conditions, (ii) a significant increase in the proline levels in the transgenic plants was observed in dry soils, and (iii) a dramatic increase in the lipid peroxidation in the untransformed controls in drier soils. Most of the biochemical parameters related to the antioxidative machinery in the tested peanut transgenics were triggered by the overexpression of AtDREB1A that appeared to differ from the untransformed controls. The antioxidants showed a negative correlation with the fraction of transpirable soil water (FTSW) thresholds, where the normalized transpiration rate (NTR) started decreasing in the tested plants. However, no significant relationship was observed between any of these biochemical indicators and the higher transpiration efficiency (TE) values found in the transgenic events. Our results show that changes in the antioxidative machinery in these transgenic peanut plants (overexpressing the AtDREB1A transcription factor) under water-limiting conditions played no causative role in improved TE.

  6. Age-related differences in signaling efficiency of human lens cells underpin differential wound healing response rates following cataract surgery.

    Science.gov (United States)

    Dawes, Lucy Jean; Duncan, George; Wormstone, Ian Michael

    2013-01-14

    Cataract surgery is blighted by posterior capsule opacification (PCO), which is more severe and frequent in the young than the elderly (>60 years). Our aim was to understand the biological basis for these age-related differences in PCO/wound healing rates. Human capsular bags were prepared by cataract surgery on donor lenses (young [60 years] groups) and maintained in serum-free Eagle's minimum essential medium. Cell growth was determined using the MTS assay. Fibroblast growth factor (FGF) and hepatocyte growth factor (HGF) levels were determined using ELISA. Protein synthesis rates were elucidated by 35S-methionine incorporation. U0126, SB203580, and SP600125 were used to disrupt ERK-, p38-, and JNK-mediated signaling, respectively. Level of total and phospho-ERK, -c-jun, -P38, and -JNK plus cytokines were detected using a BIOPLEX array system. Following a 2-day culture period, significant decreases in IL-1β and IL-6, and increases in IL-10, IL-12, IL-13, and VEGF in the >60 years group were observed compared with their younger counterparts. Capsular bags (cells and capsule) from aged donors contained greater than or equal levels of HGF and FGF than younger counterparts and had greater rates of protein synthesis. Inhibition of ERK, p38, and JNK signaling significantly suppressed cell coverage on the posterior capsule. pERK, p-c-jun, p-p38, and pJNK were consistently lower in aged cell populations; total signaling protein expression was unaffected by age. Serum stimulation increased pERK, p-c-jun, and pJNK levels in cells of all ages; p-p38 was significantly increased in the >60 years group only. Ligand availability to cells is not a limiting factor as we age, but the ability to convert this resource into signaling activity is. We therefore propose that overall signaling efficiency is reduced as a function of age, which consequently limits wound-healing response rates after injury.

  7. High Octane Fuel: Terminal Backgrounder

    Energy Technology Data Exchange (ETDEWEB)

    Moriarty, Kristi [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-02-11

    The Bioenergy Technologies Office of the U.S. Department of Energy Office of Energy Efficiency and Renewable Energy sponsored a scoping study to assess the potential of ethanol-based high octane fuel (HOF) to reduce energy consumption and greenhouse gas emissions. When the HOF blend is made with 25%-40% ethanol by volume, this energy efficiency improvement is potentially sufficient to offset the reduced vehicle range often associated with the decreased volumetric energy density of ethanol. The purpose of this study is to assess the ability of the fuel supply chain to accommodate more ethanol at fuel terminals. Fuel terminals are midstream in the transportation fuel supply chain and serve to store and distribute fuels to end users. While there are no technical issues to storing more ethanol at fuel terminals, there are several factors that could impact the ability to deploy more ethanol. The most significant of these issues include the availability of land to add more infrastructure and accommodate more truck traffic for ethanol deliveries as well as a lengthy permitting process to erect more tanks.

  8. Operational Optimization in Port Container Terminals

    DEFF Research Database (Denmark)

    As a result of the significant increase in worldwide containerized transportation the development of efficient handling systems in marine terminals has become very important for port competitiveness. In order to optimize the productivity the total handling time for containers in the terminal must...... be minimized. An overview of the different operational problems in port container terminals is presented and an aggregated model and solution approach is shown. Next, there will be focused on the yard storage problem and a mathematical formulation and solution proposals will be presented....

  9. CONTAINER TERMINALS IN EUROPE

    Directory of Open Access Journals (Sweden)

    Bart W. WIEGMANS

    2001-01-01

    Full Text Available This paper aims to address the linkage between logistics (in particular, the management of marketing channel flows and transport markets, while also the interaction between these two markets and intermodal container terminals is analysed. The marketing channel theory is used to describe all relevant actors and flows that run through marketing channels, starting with customer needs and ending with customer satisfaction. Porter's theory of competitive advantages is used to review competitive forces in both markets. Finally, a competitor analysis is performed for the logistics and transport market. These theories are applied so as to be able to determine the competitive position of intermodal container terminals with a view to the management of marketing channel flows and the physical transport of freight flows. Hence, the central question of this paper is: Which markets are served by intermodal container terminals and with whom are they competing? At present, neither the maritime container terminals nor the continental container terminals appear to have a significant influence in the logistics service market; they concentrate mainly on the physical movement of containers (transshipment. Furthermore, maritime container terminals and continental container terminals are not dominant players in the transport service market. Our conclusion is that continental terminals are predominantly competing with unimodal road transport, with neighbouring continental terminals and with barge transport companies.

  10. Response terminated displays unload selective attention.

    Science.gov (United States)

    Roper, Zachary J J; Vecera, Shaun P

    2013-01-01

    Perceptual load theory successfully replaced the early vs. late selection debate by appealing to adaptive control over the efficiency of selective attention. Early selection is observed unless perceptual load (p-Load) is sufficiently low to grant attentional "spill-over" to task-irrelevant stimuli. Many studies exploring load theory have used limited display durations that perhaps impose artificial limits on encoding processes. We extended the exposure duration in a classic p-Load task to alleviate temporal encoding demands that may otherwise tax mnemonic consolidation processes. If the load effect arises from perceptual demands alone, then freeing-up available mnemonic resources by extending the exposure duration should have little effect. The results of Experiment 1 falsify this prediction. We observed a reliable flanker effect under high p-Load, response-terminated displays. Next, we orthogonally manipulated exposure duration and task-relevance. Counter-intuitively, we found that the likelihood of observing the flanker effect under high p-Load resides with the duration of the task-relevant array, not the flanker itself. We propose that stimulus and encoding demands interact to produce the load effect. Our account clarifies how task parameters differentially impinge upon cognitive processes to produce attentional "spill-over" by appealing to visual short-term memory as an additional processing bottleneck when stimuli are briefly presented.

  11. Response terminated displays unload selective attention

    Directory of Open Access Journals (Sweden)

    Zachary Joseph Jackson Roper

    2013-12-01

    Full Text Available Perceptual load theory successfully replaced the early versus late selection debate by appealing to adaptive control over the efficiency of selective attention. Early selection is observed unless perceptual load (p-Load is sufficiently low to grant attentional ‘spill-over‘ to task-irrelevant stimuli. Many studies exploring load theory have used limited display durations that perhaps impose artificial limits on encoding processes. We extended the exposure duration in a classic p-Load task to alleviate temporal encoding demands that may otherwise tax mnemonic consolidation processes. If the load effect arises from perceptual demands alone, then freeing-up available mnemonic resources by extending the exposure duration should have little effect. The results of Experiment 1 falsify this prediction. We observed a reliable flanker effect under high p-Load, response-terminated displays. Next, we orthogonally manipulated exposure duration and task-relevance. Counter-intuitively, we found that the likelihood of observing the flanker effect under high p-Load resides with the duration of the task-relevant array, not the flanker itself. We propose that stimulus and encoding demands interact to produce the load effect. Our account clarifies how task parameters differentially impinge upon cognitive processes to produce attentional ‘spill-over’ by appealing to visual short-term memory as an additional processing bottleneck when stimuli are briefly presented.

  12. Lazy Productivity via Termination

    NARCIS (Netherlands)

    Endrullis, J.; Hendriks, R.D.A.

    2011-01-01

    We present a procedure for transforming strongly sequential constructor-based term rewriting systems (TRSs) into context-sensitive TRSs in such a way that productivity of the input system is equivalent to termination of the output system. Thereby automated termination provers become available for

  13. Termination of cycle rewriting

    NARCIS (Netherlands)

    Zantema, H.; König, B.; Bruggink, H.J.S.; Dowek, G.

    2014-01-01

    String rewriting can not only be applied on strings, but also on cycles and even on general graphs. In this paper we investigate termination of string rewriting applied on cycles, shortly denoted as cycle rewriting, which is a strictly stronger requirement than termination on strings. Most

  14. Kitimat LNG terminal

    International Nuclear Information System (INIS)

    Schmaltz, I.; Boulton, R.

    2007-01-01

    Kitimat Liquefied Natural Gas (LNG) terminal is a terminal development company owned by Galveston LNG, a privately owned Canadian energy development company. This presentation provided information on Kitimat LNG with particular reference to its terminal located in Bish Cove on the Douglas Channel in British Columbia. This LNG terminal is reported to be the only fully permitted regasification terminal on the west coast of Canada and the United States. The presentation addressed market fundamentals including several graphs, such as world natural gas proved reserves in 2006; LNG supplements to Canadian gas supplies; global LNG demand for 2005-2020; average annual United States LNG imports; and global LNG liquefaction projects. Other market fundamentals were described, including that Kitimat is the only other approved terminal aside from the Costa Azul terminal in Mexico; Kitimat is the only west coast LNG import terminal that connects to midwest and eastern North American markets through existing gas pipelines; LNG producers are looking for destination diversification; and markets and marketers are looking for supply diversification. The authors noted that by 2010, western Canadian gas demand will exceed Californian demand. Other topics that were discussed in the presentation included Canadian natural gas field receipts; unadjusted bitumen production outlook; oil sands gas demand; forward basis fundamentals; and the commercial drivers of the Kitimat LNG terminal. The presentation also discussed the pacific trail pipelines, a partnership between Galveston LNG and Pacific Northern Gas to develop the natural gas transmission line from Kitimat to Summit. The presentation concluded with a discussion of the benefits of Kitimat LNG terminal such as providing access to the largest natural gas markets in the world via major gas transmission lines with spare capacity. figs

  15. Non-fiscal price incentives. The energy-efficiency impact of differentiated energy prices; Niet-fiscale prijsprikkels. Onderzoek naar het besparingseffect van gedifferentieerde energieprijzen

    Energy Technology Data Exchange (ETDEWEB)

    Leguijt, C.; Blom, M.B.J.; Schepers, B.L.; Warringa, G.E.A.

    2012-02-15

    An exploratory study has been carried out on the potential impact of non-fiscal energy incentives. The study will feed into the Dutch government policies on energy efficiency in the built environment. The study takes in both electricity and gas, and private dwellings as well as utility buildings. The following non-fiscal price incentives were considered: (1) consumer prices indexed to consumption volume; (2) consumer prices indexed to time of consumption; (3) the energy-efficiency impact of 'autonomous' increases in energy prices. The energy-efficiency effects of price changes (options 1 and 3) were calculated on the basis of price elasticities, while for option 2 use was made of the results of the Social Cost-Benefit Analysis of Smart Grids carried out by CE Delft in collaboration with KEMA. The conclusions of the study are as follows: (a) Although differentiating consumer prices by consumption volume may yield energy savings of up to 2%, this would require market agreements in breach of the competition rules underpinning the liberalised energy market. This option is therefore unfeasible via consumer prices; (b) The energy savings accruing from indexing consumer prices to time of consumption are uncertain, as the main impact will be a temporal shift in consumption. This option is highly feasible, as such differentiation will in all likelihood evolve of its own accord with the roll-out of smart meters and smart grids; (c) The energy-efficiency impact of autonomous energy price rises is 0.2 to 0.4% per annum [Dutch] CE Delft heeft in opdracht van het Ministerie van Binnenlandse Zaken en Koninkrijkrelaties (BZK) een verkenning uitgevoerd naar de mogelijkheden voor niet-fiscale energieprijsprikkels. De studie maakt onderdeel uit van het plan van aanpak energiebesparing gebouwde omgeving van BZK. De verkenning betreft zowel elektriciteit als gas, en zowel huishoudens als utiliteitbouw. De niet-fiscale prijsprikkels die zijn verkend betreffen: (1

  16. TECHNICAL EFFICIENCY AND IMPACT EVALUATION DIFFERENTIALS BETWEEN THE ADOPTERS AND NON-ADOPTERS OF NERICA IN THE SIX BASELINE STATES IN NIGERIA

    Directory of Open Access Journals (Sweden)

    Abiodun Elijah OBAYELU

    2017-04-01

    Full Text Available The study examined the adoption rate of New Rice for Africa (NERICA, technical efficiency differentials of production of these varieties between adopters and non-adopters and the determinants. It further analysed the impact of adoption of NERICA on area cultivated, output, yield, expenditure and total income of rice farmers in the NERICA baseline states in Nigeria. To achieve the objectives, it employed the descriptive statistics, stochastic production frontier and counterfactual outcomes framework of modern evaluation technique (the Local Average Treatment Effect to analyse 621 rice farmers across the six NERICA baseline states in Nigeria in 2012. The findings show that NERICA adopters were more technically efficient than the non-adopters. In addition, adoption of NERICA was found to significantly increase the areas of land cultivated, output, yield, household expenditure, per capita household expenditure and total income among NERICA adopters by 1.2ha (p < 0.01, 1998.2kg (p< 0.01, 191.2kg/ha (p < 0.1, N13,222.63≈$66.4 (p < 0.05, N2,015.6≈$10.1 (p < 0.05 and N145,098.7 ≈$728.0 (p < 0.01 respectively despite their high level of inefficiency (39 percent by the adopters. The positive impact of NERICA adoption on rice yields, poverty status measured by the per capita household expenditure and total farm income of farmers is a clear indication that NERICA has the potential to increase rice productivity, reduce poverty and food insecurity. NERICA adoption rate will rise if more farmers are aware of the varieties in the study. Farmers who had adopted, and government at all levels should therefore intensify their efforts to encourage others rice farmers possibly through the extension agents on the need to grow NERICA varieties so as to increase rice production level, reduce rice importation and ensure a sustainable rice production.

  17. Concept Layout Model of Transportation Terminals

    Directory of Open Access Journals (Sweden)

    Li-ya Yao

    2012-01-01

    Full Text Available Transportation terminal is the key node in transport systems. Efficient terminals can improve operation of passenger transportation networks, adjust the layout of public transportation networks, provide a passenger guidance system, and regulate the development of commercial forms, as well as optimize the assembly and distribution of modern logistic modes, among others. This study aims to clarify the relationship between the function and the structure of transportation terminals and establish the function layout design. The mapping mechanism of demand, function, and structure was analyzed, and a quantitative relationship between function and structure was obtained from a design perspective. Passenger demand and terminal structure were decomposed into several demand units and structural elements following the principle of reverse engineering. The relationship maps between these two kinds of elements were then analyzed. Function-oriented concept layout model of transportation terminals was established using the previous method. Thus, a technique in planning and design of transportation structures was proposed. Meaningful results were obtained from the optimization of transportation terminal facilities, which guide the design of the functional layout of transportation terminals and improve the development of urban passenger transportation systems.

  18. Nonleaking battery terminals.

    Science.gov (United States)

    Snider, W. E.; Nagle, W. J.

    1972-01-01

    Three different terminals were designed for usage in a 40 ampere/hour silver zinc battery which has a 45% KOH by weight electrolyte in a plastic battery case. Life tests, including thermal cycling, electrical charge and discharge for up to three years duration, were conducted on these three different terminal designs. Tests for creep rate and tensile strength were conducted on the polyphenylene oxide plastic battery cases. Some cases were unused and others containing KOH electrolyte were placed on life tests. The design and testing of nonleaking battery terminals for use with a KOH electrolyte in a plastic case are considered.

  19. Hydrogen terminal solubility in Zircaloy-4

    International Nuclear Information System (INIS)

    Vizcaino, Pablo; Banchik, Abrahan D.

    1999-01-01

    Terminal solubility temperature of hydrogen in zirconium and its alloys is an important parameter because hydrides precipitation embrittled these materials making them susceptible to the phenomenon known as retarded hydrogen cracking. This work continues the study presented in the 25 AATN Meeting. Within this framework, a study focused on determining these curves in recrystallized Zircaloy-4, using scanning differential calorimetric technique. Terminal solubility curves for Zircaloy-4 were constructed within a concentration range from 40 to 640 ppm in hydrogen weight and comparisons with results obtained by other authors were made. (author)

  20. Nontraumatic terminal ileal perforation

    Directory of Open Access Journals (Sweden)

    Wani Rauf A

    2006-03-01

    Full Text Available Abstract Background There is still confusion and controversy over the diagnosis and optimal surgical treatment of non traumatic terminal ileal perforation-a cause of obscure peritonitis. Methods This study was a prospective study aimed at evaluating the clinical profile, etiology and optimal surgical management of patients with nontraumatic terminal ileal perforation. Results There were 79 cases of nontraumatic terminal ileal perforation; the causes for perforation were enteric fever(62%, nonspecific inflammation(26%, obstruction(6%, tuberculosis(4% and radiation enteritis (1%. Simple closure of the perforation (49% and end to side ileotransverse anastomosis(42% were the mainstay of the surgical management. Conclusion Terminal ileal perforation should be suspected in all cases of peritonitis especially in developing countries and surgical treatment should be optimized taking various accounts like etiology, delay in surgery and operative findings into consideration to reduce the incidence of deadly complications like fecal fistula.

  1. Terminated Multifamily Mortgages Database

    Data.gov (United States)

    Department of Housing and Urban Development — This dataset includes all terminated HUD Multifamily mortgages except those from the Hospital Mortgage Insurance Program. It includes the Holder and Servicer at the...

  2. Coal terminal directory

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-06-15

    The directory gives a comprehensive listing of the world's coal terminals, in a total of 50 countries including information on throughput, facilities, storage capacity, and vessel size limitation.

  3. Visual communication and terminal equipment

    International Nuclear Information System (INIS)

    Kang, Cheol Hui

    1988-06-01

    This book is divided two parts about visual communication and terminal equipment. The first part introduces visual communication, which deals with foundation of visual communication, technique of visual communication, equipment of visual communication, a facsimile and pictorial image system. The second part contains terminal equipment such as telephone, terminal equipment for data transmission on constitution and constituent of terminal equipment for data transmission, input device and output device, terminal device and up-to-date terminal device.

  4. Visual communication and terminal equipment

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Cheol Hui

    1988-06-15

    This book is divided two parts about visual communication and terminal equipment. The first part introduces visual communication, which deals with foundation of visual communication, technique of visual communication, equipment of visual communication, a facsimile and pictorial image system. The second part contains terminal equipment such as telephone, terminal equipment for data transmission on constitution and constituent of terminal equipment for data transmission, input device and output device, terminal device and up-to-date terminal device.

  5. Tandem Terminal Ion Source

    International Nuclear Information System (INIS)

    Harper, G.C.; Lindner, C.E.; Myers, A.W.; Wechel, T.D. van

    2000-01-01

    OAK-B135 Tandem Terminal Ion Source. The terminal ion source (TIS) was used in several experiments during this reporting period, all for the 7 Be(γ) 8 B experiment. Most of the runs used 1 H + at terminal voltages from 0.3 MV to 1.5 MV. One of the runs used 2 H + at terminal voltage of 1.4 MV. The other run used 4 He + at a terminal voltage of 1.37 MV. The list of experiments run with the TIS to date is given in table 1 below. The tank was opened four times for unscheduled source repairs. On one occasion the tank was opened to replace the einzel lens power supply which had failed. The 10 kV unit was replaced with a 15 kV unit. The second time the tank was opened to repair the extractor supply which was damaged by a tank spark. On the next occasion the tank was opened to replace a source canal which had sputtered away. Finally, the tank was opened to replace the discharge bottle which had been coated with aluminum sputtered from the exit canal

  6. Tandem Terminal Ion Source

    International Nuclear Information System (INIS)

    None

    2000-01-01

    OAK-B135 Tandem Terminal Ion Source. The terminal ion source (TIS) was used in several experiments during this reporting period, all for the(sup 7)Be((gamma))(sup 8)B experiment. Most of the runs used(sup 1)H(sup+) at terminal voltages from 0.3 MV to 1.5 MV. One of the runs used(sup 2)H(sup+) at terminal voltage of 1.4 MV. The other run used(sup 4)He(sup+) at a terminal voltage of 1.37 MV. The list of experiments run with the TIS to date is given in table 1 below. The tank was opened four times for unscheduled source repairs. On one occasion the tank was opened to replace the einzel lens power supply which had failed. The 10 kV unit was replaced with a 15 kV unit. The second time the tank was opened to repair the extractor supply which was damaged by a tank spark. On the next occasion the tank was opened to replace a source canal which had sputtered away. Finally, the tank was opened to replace the discharge bottle which had been coated with aluminum sputtered from the exit canal

  7. Two separable functional domains of simian virus 40 large T antigen: carboxyl-terminal region of simian virus 40 large T antigen is required for efficient capsid protein synthesis.

    Science.gov (United States)

    Tornow, J; Polvino-Bodnar, M; Santangelo, G; Cole, C N

    1985-01-01

    The carboxyl-terminal portion of simian virus 40 large T antigen is essential for productive infection of CV-1 and CV-1p green monkey kidney cells. Mutant dlA2459, lacking 14 base pairs at 0.193 map units, was positive for viral DNA replication, but unable to form plaques in CV-1p cells (J. Tornow and C.N. Cole, J. Virol. 47:487-494, 1983). In this report, the defect of dlA2459 is further defined. Simian virus 40 late mRNAs were transcribed, polyadenylated, spliced, and transported in dlA2459-infected cells, but the level of capsid proteins produced in infected CV-1 green monkey kidney cells was extremely low. dlA2459 large T antigen lacks those residues known to be required for adenovirus helper function, and the block to productive infection by dlA2459 occurs at the same stage of infection as the block to productive adenovirus infection of CV-1 cells. These results suggest that the adenovirus helper function is required for productive infection by simian virus 40. Mutant dlA2459 was able to grow on the Vero and BSC-1 lines of African green monkey kidney cells. Additional mutants affecting the carboxyl-terminal portion of large T were prepared. Mutant inv2408 contains an inversion of the DNA between the BamHI and BclI sites (0.144 to 0.189 map units). This inversion causes transposition of the carboxyl-terminal 26 amino acids of large T antigen and the carboxyl-terminal 18 amino acids of VP1. This mutant was viable, even though the essential information absent from dlA2459 large T antigen has been transferred to the carboxyl terminus of VP1 of inv2408. The VP1 polypeptide carrying this carboxyl-terminal portion of large T could overcome the defect of dlA2459. This indicates that the carboxyl terminus of large T antigen is a separate and separable functional domain. Images PMID:2982029

  8. Windows Terminal Servers Orchestration

    Science.gov (United States)

    Bukowiec, Sebastian; Gaspar, Ricardo; Smith, Tim

    2017-10-01

    Windows Terminal Servers provide application gateways for various parts of the CERN accelerator complex, used by hundreds of CERN users every day. The combination of new tools such as Puppet, HAProxy and Microsoft System Center suite enable automation of provisioning workflows to provide a terminal server infrastructure that can scale up and down in an automated manner. The orchestration does not only reduce the time and effort necessary to deploy new instances, but also facilitates operations such as patching, analysis and recreation of compromised nodes as well as catering for workload peaks.

  9. Differential Equations as Actions

    DEFF Research Database (Denmark)

    Ronkko, Mauno; Ravn, Anders P.

    1997-01-01

    We extend a conventional action system with a primitive action consisting of a differential equation and an evolution invariant. The semantics is given by a predicate transformer. The weakest liberal precondition is chosen, because it is not always desirable that steps corresponding to differential...... actions shall terminate. It is shown that the proposed differential action has a semantics which corresponds to a discrete approximation when the discrete step size goes to zero. The extension gives action systems the power to model real-time clocks and continuous evolutions within hybrid systems....

  10. The Tiny Terminators

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 6; Issue 5. The Tiny Terminators - Mosquitoes and Diseases. P K Sumodan. General Article Volume 6 Issue 5 May 2001 pp 48-55. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/006/05/0048-0055 ...

  11. Making Wireless Terminals Simpler

    DEFF Research Database (Denmark)

    Christensen, Søren Skovgaard; Popovski, Petar; De Carvalho, Elisabeth

    2005-01-01

    equalization in the downlink, which these requirements lead to. We propose to solve the problem by applying pre-processing at the base station, thereby rendering the terminal simple. We establish a general MIMO block transmission model, and derive different transmit/receive filters, based on the Linear Minimum...

  12. Trauma and termination.

    Science.gov (United States)

    Ferraro, F

    1995-02-01

    The author suggests a particular reading of the thesis put forward by Freud in 'Analysis terminable and interminable' that an effective and more definitive conclusion may be expected in analyses of cases with traumatic aetiology. This reading shifts the emphasis from the patient's history to the possibility of its crystallising in focal nuclei emerging within the analytic relationship under the pressure of the termination. The revival of separation anxieties which cannot be worked through, and their crystallisation in precipitating traumatic events, may give rise to decisive psychic work allowing the analysis to be brought to a conclusion. Two case histories are presented to show how the end of the analysis assumes the form of a new trauma, which reactivates in the present, traumatic anxieties from the patient's own infantile history. In the first case a premature birth and in the second a miscarriage, originally experienced as isolated automatic events without time or history, are relived in the terminal phase as vicissitudes of the transference, so that new meaning can be assigned to them and they can be withdrawn from the somatic cycle of repetition. The powerful tendency to act out and the intense countertransference pressure on the analyst are discussed in the light of the specificities of this phase, which is crucial to the success of the analysis. This leads to a re-examination, in the concluding notes, of some theoretical questions inherent in the problem of the termination and, in particular, to a discussion of the ambiguous concept of a natural ending.

  13. Prematurely terminated slug tests

    International Nuclear Information System (INIS)

    Karasaki, K.

    1990-07-01

    A solution of the well response to a prematurely terminated slug test (PTST) is presented. The advantages of a PTST over conventional slug tests are discussed. A systematized procedure of a PTST is proposed, where a slug test is terminated in the midpoint of the flow point, and the subsequent shut-in data is recorded and analyzed. This method requires a downhole shut-in device and a pressure transducer, which is no more than the conventional deep-well slug testing. As opposed to slug tests, which are ineffective when a skin is present, more accurate estimate of formation permeability can be made using a PTST. Premature termination also shortens the test duration considerably. Because in most cases no more information is gained by completing a slug test to the end, the author recommends that conventional slug tests be replaced by the premature termination technique. This study is part of an investigation of the feasibility of geologic isolation of nuclear wastes being carried out by the US Department of Energy and the National Cooperative for the Storage of Radioactive Waste of Switzerland

  14. NPOESS Field Terminal Updates

    Science.gov (United States)

    Heckmann, G.; Route, G.

    2009-12-01

    The National Oceanic and Atmospheric Administration (NOAA), Department of Defense (DoD), and National Aeronautics and Space Administration (NASA) are jointly acquiring the next-generation weather and environmental satellite system; the National Polar-orbiting Operational Environmental Satellite System (NPOESS). NPOESS replaces the current Polar-orbiting Operational Environmental Satellites (POES) managed by NOAA and the Defense Meteorological Satellite Program (DMSP) managed by the DoD. The NPOESS satellites carry a suite of sensors that collect meteorological, oceanographic, climatological, and solar-geophysical observations of the earth, atmosphere, and space. The ground data processing segment for NPOESS is the Interface Data Processing Segment (IDPS), developed by Raytheon Intelligence and Information Systems. The IDPS processes NPOESS satellite data to provide environmental data products (aka, Environmental Data Records or EDRs) to NOAA and DoD processing centers operated by the United States government. The IDPS will process EDRs beginning with the NPOESS Preparatory Project (NPP) and continuing through the lifetime of the NPOESS system. IDPS also provides the software and requirements for the Field Terminal Segment (FTS). NPOESS provides support to deployed field terminals by providing mission data in the Low Rate and High Rate downlinks (LRD/HRD), mission support data needed to generate EDRs and decryption keys needed to decrypt mission data during Selective data Encryption (SDE). Mission support data consists of globally relevant data, geographically constrained data, and two line element sets. NPOESS provides these mission support data via the Internet accessible Mission Support Data Server and HRD/LRD downlinks. This presentation will illustrate and describe the NPOESS capabilities in support of Field Terminal users. This discussion will include the mission support data available to Field Terminal users, content of the direct broadcast HRD and LRD

  15. Termination Criteria for Computerized Classification Testing

    Directory of Open Access Journals (Sweden)

    Nathan A. Thompson

    2011-02-01

    Full Text Available Computerized classification testing (CCT is an approach to designing tests with intelligent algorithms, similar to adaptive testing, but specifically designed for the purpose of classifying examinees into categories such as - pass- and - fail.- Like adaptive testing for point estimation of ability, the key component is the termination criterion, namely the algorithm that decides whether to classify the examinee and end the test or to continue and administer another item. This paper applies a newly suggested termination criterion, the generalized likelihood ratio (GLR, to CCT. It also explores the role of the indifference region in the specification of likelihood-ratio based termination criteria, comparing the GLR to the sequential probability ratio test. Results from simulation studies suggest that the GLR is always at least as efficient as existing methods.

  16. Reduced Expression of Siglec-7, NKG2A, and CD57 on Terminally Differentiated CD56-CD16+ Natural Killer Cell Subset Is Associated with Natural Killer Cell Dysfunction in Chronic HIV-1 Clade C Infection.

    Science.gov (United States)

    Zulu, Michael Z; Naidoo, Kewreshini K; Mncube, Zenele; Jaggernath, Manjeetha; Goulder, Philip J R; Ndung'u, Thumbi; Altfeld, Marcus; Thobakgale, Christina F

    2017-12-01

    HIV-1 viremia has been shown to induce several phenotypic and functional abnormalities in natural killer (NK) cells. To assess immune defects associated with HIV viremia, we examined NK cell function, differentiation status, and phenotypic alterations based on expression of inhibitory and activating receptors on NK cells in HIV-1 subtype C chronically infected participants from Durban, South Africa. NK cell phenotypic profiles were characterized by assessing sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7), NKG2A, and NKG2C markers on frozen peripheral blood mononuclear cells from viremic, antiretroviral therapy (ART)-naive HIV-1 chronically infected participants (n = 23), HIV-1 chronically infected participants who had been on combination antiretroviral therapy (cART) for at least 12 months (n = 23) compared with healthy donors (n = 23). NK cell differentiation was assessed by measurement of killer immunoglobulin receptor (KIR) and NKG2A expression; CD57 and CD107a measurements were carried out in HIV viremic and healthy donors. All phenotypic and functional assessments were analyzed by using multicolor flow cytometry. HIV-1-infected participants displayed greater frequencies of the CD56 - CD16 + (CD56negative) NK cell subset compared with healthy donors (p < .0001). Downregulation of Siglec-7 and NKG2A and upregulation of NKG2C were more pronounced in the CD56negative NK cell subset of viremic participants. The CD56negative subset demonstrated a differentiated (KIR + NKG2A - ) phenotype with reduced CD57 expression and lower degranulation capacity in HIV-1-infected participants compared with healthy donors. HIV-1 infection induces the expansion of the CD56negative NK cell subset marked by altered receptor expression profiles that are indicative of impaired function and may explain the overall NK cell dysfunction observed in chronic HIV-1 infection.

  17. Antecedents of Customer Relationship Termination

    DEFF Research Database (Denmark)

    Geersbro, Jens; Ritter, Thomas

    To end business relationships, or to more actively terminate relationships, has long been acknowledged as part of customer relationship management. However, compared to other elements such as initiation and maintenance of relationships, little is known about the termination of business...... relationships as a managerial task. This paper contributes by (1) developing a conceptualization of relationship termination competence and (2) analyzing its antecedents. The empirical results identify termination acceptance, definition non-customers, organizational relationship termination routines......, and motivation as significant antecedents. Because of this, managers need to develop their organizations in order to use relationship termination as a vital strategy....

  18. Synthesis and characterization of phenylethynylcarbonyl terminated novel thermosetting imide compound

    Directory of Open Access Journals (Sweden)

    H. Kimura

    2013-02-01

    Full Text Available Phenylethynyl terminated novel imide compound based on 1,3-bis(3-aminophenoxybenzene (APB and phenylethynyl trimellitic anhydride (PETA were prepared. The curing behavior of phenylethynyl terminated imide compound was investigated by differential scanning calorimetry and Fourier transform infrared spectrometry. The curing reaction of phenylethynylcarbonyl end group completed at 220°C, and proceeded much faster than that of phenylethynyl end group. Glass transition temperature of the thermosetting resin from phenylethynylcarbonyl terminated novel imide compound determined by dynamic mechanical analysis was almost the same as that of o-cresolnovolac type epoxy resin. In addition, the thermosetting resin from phenylethynylcarbonyl terminated novel imide compound exhibited excellent thermal and dimensional stabilities. These excellent properties of these phenylethynyl terminated imide compound might be due to the incorporation of alkene group or aromatic ring substitutes in the backbones, which might enhance the chain interaction (molecular packing and reduce the molecular chain mobility.

  19. Evaluation of efficiency of equipment used in the conservation of fruits and vegetables in the terminal Warehouse of Sao Paulo - CEAGESP; Avaliacao da eficiencia no uso dos equipamentos de refrigeracao utilizados na conservacao de frutas e hortalicas no entreposto terminal de Sao Paulo (CEAGESP-Companhia de Entrepostos e Armazens Gerais de Sao Paulo)

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira Neto, Josue; Ferreira, Marcos David [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Engenharia Agricola (FEAGRI); Neves Filho, Lincoln de Camargo [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Dept. de Engenharia de Alimentos; Gutierrez, Anita de Souza Dias [CEAGESP, Sao Paulo, SP (Brazil). Centro de Qualidade em Horticultura

    2004-07-01

    The shelf life of fruits and vegetables can be directly related to store temperature. At determined temperature and humidity a better conservation of the product can be achieve. The cold chain delays the aging, having its conservation guaranteed until the consumer. It was carried through in the Terminal Warehouse of Sao Paulo- CEAGESP, a research for evaluation of the condition of the cold chambers used. The cold storage equipment evaluation was measured using the follow parameters: temperature, humidity, isolation, type of equipment used, etc. It was analyzed, chambers used for cold storage, using thermal load calculation. Apple and pears were the most stored commodities in CEAGESP, 50 % and bananas the second one (31,4%). Based in the average volume of commercialization, it was observed that 57% of the motors were over dimensioned. (author)

  20. One-dimensional TRFLP-SSCP is an effective DNA fingerprinting strategy for soil Archaea that is able to simultaneously differentiate broad taxonomic clades based on terminal fragment length polymorphisms and closely related sequences based on single stranded conformation polymorphisms.

    Science.gov (United States)

    Swanson, Colby A; Sliwinski, Marek K

    2013-09-01

    DNA fingerprinting methods provide a means to rapidly compare microbial assemblages from environmental samples without the need to first cultivate species in the laboratory. The profiles generated by these techniques are able to identify statistically significant temporal and spatial patterns, correlations to environmental gradients, and biological variability to estimate the number of replicates for clone libraries or next generation sequencing (NGS) surveys. Here we describe an improved DNA fingerprinting technique that combines terminal restriction fragment length polymorphisms (TRFLP) and single stranded conformation polymorphisms (SSCP) so that both can be used to profile a sample simultaneously rather than requiring two sequential steps as in traditional two-dimensional (2-D) gel electrophoresis. For the purpose of profiling Archaeal 16S rRNA genes from soil, the dynamic range of this combined 1-D TRFLP-SSCP approach was superior to TRFLP and SSCP. 1-D TRFLP-SSCP was able to distinguish broad taxonomic clades with genetic distances greater than 10%, such as Euryarchaeota and the Thaumarchaeal clades g_Ca. Nitrososphaera (formerly 1.1b) and o_NRP-J (formerly 1.1c) better than SSCP. In addition, 1-D TRFLP-SSCP was able to simultaneously distinguish closely related clades within a genus such as s_SCA1145 and s_SCA1170 better than TRFLP. We also tested the utility of 1-D TRFLP-SSCP fingerprinting of environmental assemblages by comparing this method to the generation of a 16S rRNA clone library of soil Archaea from a restored Tallgrass prairie. This study shows 1-D TRFLP-SSCP fingerprinting provides a rapid and phylogenetically informative screen of Archaeal 16S rRNA genes in soil samples. © 2013.

  1. Review paper. Terminal lucidity

    Directory of Open Access Journals (Sweden)

    Chiriboga-Oleszczak Boris Alejandro

    2017-03-01

    Full Text Available Terminal lucidity is a term used in the medical literature to determine the improvement of mental functioning shortly before death, even among patients with serious and long-term disorders. In 19th century, cases of mind clarity recovery shortly before death, were often recognized by doctors and interpreted as a sign of an impending death. In 20th century, the interest in this phenomenon decreased and then, virtually disappear. In recent years, on the wave of publications concerning near death experiences and related events such as the end of life experiences, papers about the improvement of mental functioning shortly before death, exponentially grew and got a new name, terminal lucidity. In this paper, an overview of the available literature is presented to outline the historical, phenomenological and clinical picture of this phenomenon and its possible implications for medical care and future studies.

  2. Scandium Terminal Imido Chemistry.

    Science.gov (United States)

    Lu, Erli; Chu, Jiaxiang; Chen, Yaofeng

    2018-02-20

    Research into transition metal complexes bearing multiply bonded main-group ligands has developed into a thriving and fruitful field over the past half century. These complexes, featuring terminal M═E/M≡E (M = transition metal; E = main-group element) multiple bonds, exhibit unique structural properties as well as rich reactivity, which render them attractive targets for inorganic/organometallic chemists as well as indispensable tools for organic/catalytic chemists. This fact has been highlighted by their widespread applications in organic synthesis, for example, as olefin metathesis catalysts. In the ongoing renaissance of transition metal-ligand multiple-bonding chemistry, there have been reports of M═E/M≡E interactions for the majority of the metallic elements of the periodic table, even some actinide metals. In stark contrast, the largest subgroup of the periodic table, rare-earth metals (Ln = Sc, Y, and lanthanides), have been excluded from this upsurge. Indeed, the synthesis of terminal Ln═E/Ln≡E multiple-bonding species lagged behind that of the transition metal and actinide congeners for decades. Although these species had been pursued since the discovery of a rare-earth metal bridging imide in 1991, such a terminal (nonpincer/bridging hapticities) Ln═E/Ln≡E bond species was not obtained until 2010. The scarcity is mainly attributed to the energy mismatch between the frontier orbitals of the metal and the ligand atoms. This renders the putative terminal Ln═E/Ln≡E bonds extremely reactive, thus resulting in the formation of aggregates and/or reaction with the ligand/environment, quenching the multiple-bond character. In 2010, the stalemate was broken by the isolation and structural characterization of the first rare-earth metal terminal imide-a scandium terminal imide-by our group. The double-bond character of the Sc═N bond was unequivocally confirmed by single-crystal X-ray diffraction. Theoretical investigations revealed the presence

  3. Differential Effects of Ethanol on c-Jun N-Terminal Kinase, 14-3-3 Proteins, and Bax in Postnatal Day 4 and Postnatal Day 7 Rat Cerebellum

    Science.gov (United States)

    Heaton, Marieta Barrow; Paiva, Michael; Kubovic, Stacey; Kotler, Alexandra; Rogozinski, Jonathan; Swanson, Eric; Madorsky, Vladimir; Posados, Michelle

    2011-01-01

    These studies investigated ethanol effects on upstream cellular elements and interactions which contribute to Bax-related apoptosis in neonatal rat cerebellum at ages of peak ethanol sensitivity (postnatal day 4 [P4]), compared to later ages of relative resistance (P7). Analyses were made of basal levels of the pro-apoptotic c-jun N-termimal kinase (JNK), Bax, and the 14-3-3 anchoring proteins, as well as the responsiveness of these substances to ethanol at P4 versus P7. Dimerization of Bax with 14-3-3 was also investigated at the two ages following ethanol treatment, a process which sequesters Bax in the cytosol, thus inhibiting its mitochondrial translocation and disruption of the mitochondrial membrane potential. Cultured cerebellar granule cells were used to examine the protective potential of JNK inhibition on ethanol-mediated cell death. Basal levels of JNK were significantly higher at P4 than P7, but no differences in the other proteins were found. Activated JNK, and cytosolic and mitochondrially-translocated Bax were increased in P4 but not P7 animals following ethanol exposure, while protective 14-3-3 proteins were increased only at P7. Ethanol treatment resulted in decreases in Bax:14-3-3 heterodimers at P4, but not at P7. Inhibition of JNK activity in vitro provided partial protection against ethanol neurotoxicity. Thus, differential temporal vulnerability to ethanol in this CNS region correlates with differences in both levels of apoptosis-related substances (e.g., JNK), and differential cellular responsiveness, favoring apoptosis at the most sensitive age and survival at the resistant age. The upstream elements contributing to this vulnerability can be targets for future therapeutic strategies. PMID:22169498

  4. Terminal-Dependent Statistical Inference for the FBSDEs Models

    Directory of Open Access Journals (Sweden)

    Yunquan Song

    2014-01-01

    Full Text Available The original stochastic differential equations (OSDEs and forward-backward stochastic differential equations (FBSDEs are often used to model complex dynamic process that arise in financial, ecological, and many other areas. The main difference between OSDEs and FBSDEs is that the latter is designed to depend on a terminal condition, which is a key factor in some financial and ecological circumstances. It is interesting but challenging to estimate FBSDE parameters from noisy data and the terminal condition. However, to the best of our knowledge, the terminal-dependent statistical inference for such a model has not been explored in the existing literature. We proposed a nonparametric terminal control variables estimation method to address this problem. The reason why we use the terminal control variables is that the newly proposed inference procedures inherit the terminal-dependent characteristic. Through this new proposed method, the estimators of the functional coefficients of the FBSDEs model are obtained. The asymptotic properties of the estimators are also discussed. Simulation studies show that the proposed method gives satisfying estimates for the FBSDE parameters from noisy data and the terminal condition. A simulation is performed to test the feasibility of our method.

  5. Nurses' attitudes to terminally ill patients.

    Science.gov (United States)

    Román, E M; Sorribes, E; Ezquerro, O

    2001-05-01

    The care of terminally ill patients is a challenge for nurses that has raised special interest in recent years. Several studies have shown a stereotyped negative attitude in nurses towards terminally ill patients. However, all have used methods with several limitations. The aim of the study presented in this paper was to identify the nurses' attitude to the terminally ill patient in Catalonia, Spain, and the relationship of this attitude to different socio-demographic data (type of centre, shift, years of experience, age and sex) by means of a new quantitative method based on the free word-association test. One hundred and seventy-five nurses working in 18 hospitals and hospices in Catalonia, Spain were included in the study. Data were analysed by the Associative Semantic Field Differential method by means of the computer programme CONTEXT and a quantitative evaluation of the degree of attitudes positivity was obtained. The study revealed a general slight negative trend in attitudes towards the terminally ill patient. A more positive attitude was observed in older caregivers and in women. The positivity in attitude decreased from morning to night shift. No differences were observed between nurses working in hospitals and those working in hospices. We conclude that nursing attitudes can be analysed by methods such as that used in this study. Attempts can be made to modify this attitude in caregivers by means of training programmes and stimulating awareness of an adequate professional approach.

  6. LNG TERMINAL SAFE OPERATION MANAGEMENT

    OpenAIRE

    Andrzej ADAMKIEWICZ; Włodzimierz KAMIŃSKI

    2012-01-01

    This article presents the significance of LNG terminal safety issues in natural gas sea transport. It shows particular requirements for LNG transmission installations resulting from the specific properties of LNG. Out of the multi‐layer critical safety areas comprising structural elements of the terminal safety system, possibilities to decrease the risk of emergency occurrence on LNG terminals have been selected. Tasks performed by the LNG terminal, together with its own personnel and the out...

  7. Efficient and Cost-Effective Generation of Mature Neurons From Human Induced Pluripotent Stem Cells

    OpenAIRE

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

    2014-01-01

    The authors describe a feeder-free method of generating induced pluripotent stem cells by 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. This specific and efficient single-step strategy allows the production of mature neurons in 20–40 days with multiple applications, especially for modeling human pathologies.

  8. Efficient generation of transgene- and feeder-free induced pluripotent stem cells from human dental mesenchymal stem cells and their chemically defined differentiation into cardiomyocytes.

    Science.gov (United States)

    Tan, Xiaobing; Dai, Qingli; Guo, Tao; Xu, Jingshu; Dai, Qingyuan

    2018-01-22

    Advance in stem cell research resulted in several processes to generate induced pluripotent stem cells (iPSCs) from adult somatic cells. In our previous study, the reprogramming of iPSCs from human dental mesenchymal stem cells (MSCs) including SCAP and DPSCs, has been reported. Herein, safe iPSCs were reprogrammed from SCAP and DPSCs using non-integrating RNA virus vector, which is an RNA virus carrying no risk of altering host genome. DPSCs- and SCAP-derived iPSCs exhibited the characteristics of the classical morphology with human embryonic stem cells (hESCs) without integration of foreign genes, indicating the potential of their clinical application. Moreover, induced PSCs showed the capacity of self-renewal and differentiation into cardiac myocytes. We have achieved the differentiation of hiPSCs to cardiomyocytes lineage under serum and feeder-free conditions, using a chemically defined medium CDM3. In CDM3, hiPSCs differentiation is highly generating cardiomyocytes. The results showed this protocol produced contractile sheets of up to 97.2% TNNT2 cardiomyocytes after purification. Furthermore, derived hiPSCs differentiated to mature cells of the three embryonic germ layers in vivo and in vitro of beating cardiomyocytes. The above whole protocol enables the generation of large scale of highly pure cardiomyocytes as needed for cellular therapy. Copyright © 2017. Published by Elsevier Inc.

  9. Development of an efficient fungal DNA extraction method to be used in random amplified polymorphic DNA-PCR analysis to differentiate cyclopiazonic acid mold producers.

    Science.gov (United States)

    Sánchez, Beatriz; Rodríguez, Mar; Casado, Eva M; Martín, Alberto; Córdoba, Juan J

    2008-12-01

    A variety of previously established mechanical and chemical treatments to achieve fungal cell lysis combined with a semiautomatic system operated by a vacuum pump were tested to obtain DNA extract to be directly used in randomly amplified polymorphic DNA (RAPD)-PCR to differentiate cyclopiazonic acid-producing and -nonproducing mold strains. A DNA extraction method that includes digestion with proteinase K and lyticase prior to using a mortar and pestle grinding and a semiautomatic vacuum system yielded DNA of high quality in all the fungal strains and species tested, at concentrations ranging from 17 to 89 ng/microl in 150 microl of the final DNA extract. Two microliters of DNA extracted with this method was directly used for RAPD-PCR using primer (GACA)4. Reproducible RAPD fingerprints showing high differences between producer and nonproducer strains were observed. These differences in the RAPD patterns did not differentiate all the strains tested in clusters by cyclopiazonic acid production but may be very useful to distinguish cyclopiazonic acid producer strains from nonproducer strains by a simple RAPD analysis. Thus, the DNA extracts obtained could be used directly without previous purification and quantification for RAPD analysis to differentiate cyclopiazonic acid producer from nonproducer mold strains. This combined analysis could be adaptable to other toxigenic fungal species to enable differentiation of toxigenic and non-toxigenic molds, a procedure of great interest in food safety.

  10. Human Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells in Phenotypic Screening: A Transforming Growth Factor-β Type 1 Receptor Kinase Inhibitor Induces Efficient Cardiac Differentiation.

    Science.gov (United States)

    Drowley, Lauren; Koonce, Chad; Peel, Samantha; Jonebring, Anna; Plowright, Alleyn T; Kattman, Steven J; Andersson, Henrik; Anson, Blake; Swanson, Bradley J; Wang, Qing-Dong; Brolen, Gabriella

    2016-02-01

    Several progenitor cell populations have been reported to exist in hearts that play a role in cardiac turnover and/or repair. Despite the presence of cardiac stem and progenitor cells within the myocardium, functional repair of the heart after injury is inadequate. Identification of the signaling pathways involved in the expansion and differentiation of cardiac progenitor cells (CPCs) will broaden insight into the fundamental mechanisms playing a role in cardiac homeostasis and disease and might provide strategies for in vivo regenerative therapies. To understand and exploit cardiac ontogeny for drug discovery efforts, we developed an in vitro human induced pluripotent stem cell-derived CPC model system using a highly enriched population of KDR(pos)/CKIT(neg)/NKX2.5(pos) CPCs. Using this model system, these CPCs were capable of generating highly enriched cultures of cardiomyocytes under directed differentiation conditions. In order to facilitate the identification of pathways and targets involved in proliferation and differentiation of resident CPCs, we developed phenotypic screening assays. Screening paradigms for therapeutic applications require a robust, scalable, and consistent methodology. In the present study, we have demonstrated the suitability of these cells for medium to high-throughput screens to assess both proliferation and multilineage differentiation. Using this CPC model system and a small directed compound set, we identified activin-like kinase 5 (transforming growth factor-β type 1 receptor kinase) inhibitors as novel and potent inducers of human CPC differentiation to cardiomyocytes. Significance: Cardiac disease is a leading cause of morbidity and mortality, with no treatment available that can result in functional repair. This study demonstrates how differentiation of induced pluripotent stem cells can be used to identify and isolate cell populations of interest that can translate to the adult human heart. Two separate examples of phenotypic

  11. Efficient differentiation of steroidogenic and germ-like cells from epigenetically-related iPSCs derived from ovarian granulosa cells.

    Directory of Open Access Journals (Sweden)

    Raymond Anchan

    Full Text Available To explore restoration of ovarian function using epigenetically-related, induced pluripotent stem cells (iPSCs, we functionally evaluated the epigenetic memory of novel iPSC lines, derived from mouse and human ovarian granulosa cells (GCs using c-Myc, Klf4, Sox2 and Oct4 retroviral vectors. The stem cell identity of the mouse and human GC-derived iPSCs (mGriPSCs, hGriPSCs was verified by demonstrating embryonic stem cell (ESC antigen expression using immunocytochemistry and RT-PCR analysis, as well as formation of embryoid bodies (EBs and teratomas that are capable of differentiating into cells from all three germ layers. GriPSCs' gene expression profiles associate more closely with those of ESCs than of the originating GCs as demonstrated by genome-wide analysis of mRNA and microRNA. A comparative analysis of EBs generated from three different mouse cell lines (mGriPSCs; fibroblast-derived iPSC, mFiPSCs; G4 embryonic stem cells, G4 mESCs revealed that differentiated mGriPSC-EBs synthesize 10-fold more estradiol (E2 than either differentiated FiPSC- or mESC-EBs under identical culture conditions. By contrast, mESC-EBs primarily synthesize progesterone (P4 and FiPSC-EBs produce neither E2 nor P4. Differentiated mGriPSC-EBs also express ovarian markers (AMHR, FSHR, Cyp19a1, ER and Inha as well as markers of early gametogenesis (Mvh, Dazl, Gdf9, Boule and Zp1 more frequently than EBs of the other cell lines. These results provide evidence of preferential homotypic differentiation of mGriPSCs into ovarian cell types. Collectively, our data support the hypothesis that generating iPSCs from the desired tissue type may prove advantageous due to the iPSCs' epigenetic memory.

  12. LNG TERMINAL SAFE OPERATION MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Andrzej ADAMKIEWICZ

    2012-07-01

    Full Text Available This article presents the significance of LNG terminal safety issues in natural gas sea transport. It shows particular requirements for LNG transmission installations resulting from the specific properties of LNG. Out of the multi‐layer critical safety areas comprising structural elements of the terminal safety system, possibilities to decrease the risk of emergency occurrence on LNG terminals have been selected. Tasks performed by the LNG terminal, together with its own personnel and the outside one, have been defined. General theses for LNG terminal safety have been formulated.

  13. Terminal weather information management

    Science.gov (United States)

    Lee, Alfred T.

    1990-01-01

    Since the mid-1960's, microburst/windshear events have caused at least 30 aircraft accidents and incidents and have killed more than 600 people in the United States alone. This study evaluated alternative means of alerting an airline crew to the presence of microburst/windshear events in the terminal area. Of particular interest was the relative effectiveness of conventional and data link ground-to-air transmissions of ground-based radar and low-level windshear sensing information on microburst/windshear avoidance. The Advanced Concepts Flight Simulator located at Ames Research Center was employed in a line oriented simulation of a scheduled round-trip airline flight from Salt Lake City to Denver Stapleton Airport. Actual weather en route and in the terminal area was simulated using recorded data. The microburst/windshear incident of July 11, 1988 was re-created for the Denver area operations. Six experienced airline crews currently flying scheduled routes were employed as test subjects for each of three groups: (1) A baseline group which received alerts via conventional air traffic control (ATC) tower transmissions; (2) An experimental group which received alerts/events displayed visually and aurally in the cockpit six miles (approx. 2 min.) from the microburst event; and (3) An additional experimental group received displayed alerts/events 23 linear miles (approx. 7 min.) from the microburst event. Analyses of crew communications and decision times showed a marked improvement in both situation awareness and decision-making with visually displayed ground-based radar information. Substantial reductions in the variability of decision times among crews in the visual display groups were also found. These findings suggest that crew performance will be enhanced and individual differences among crews due to differences in training and prior experience are significantly reduced by providing real-time, graphic display of terminal weather hazards.

  14. Conditioned Media from Human Adipose Tissue-Derived Mesenchymal Stem Cells and Umbilical Cord-Derived Mesenchymal Stem Cells Efficiently Induced the Apoptosis and Differentiation in Human Glioma Cell Lines In Vitro

    Directory of Open Access Journals (Sweden)

    Chao Yang

    2014-01-01

    Full Text Available Human mesenchymal stem cells (MSCs have an intrinsic property for homing towards tumor sites and can be used as tumor-tropic vectors for tumor therapy. But very limited studies investigated the antitumor properties of MSCs themselves. In this study we investigated the antiglioma properties of two easily accessible MSCs, namely, human adipose tissue-derived mesenchymal stem cells (ASCs and umbilical cord-derived mesenchymal stem cells (UC-MSCs. We found (1 MSC conditioned media can significantly inhibit the growth of human U251 glioma cell line; (2 MSC conditioned media can significantly induce apoptosis in human U251 cell line; (3 real-time PCR experiments showed significant upregulation of apoptotic genes of both caspase-3 and caspase-9 and significant downregulation of antiapoptotic genes such as survivin and XIAP after MSC conditioned media induction in U 251 cells; (4 furthermore, MSCs conditioned media culture induced rapid and complete differentiation in U251 cells. These results indicate MSCs can efficiently induce both apoptosis and differentiation in U251 human glioma cell line. Whereas UC-MSCs are more efficient for apoptosis induction than ASCs, their capability of differentiation induction is not distinguishable from each other. Our findings suggest MSCs themselves have favorable antitumor characteristics and should be further explored in future glioma therapy.

  15. Improved cell therapy protocols for Parkinson's disease based on differentiation efficiency and safety of hESC-, hiPSC-, and non-human primate iPSC-derived dopaminergic neurons

    DEFF Research Database (Denmark)

    Sundberg, Maria; Bogetofte, Helle; Lawson, Tristan

    2013-01-01

    of safety and efficacy of stem cell-derived DA neurons. The aim of this study was to improve the safety of human- and non-human primate iPSC (PiPSC)-derived DA neurons. According to our results, NCAM(+) /CD29(low) sorting enriched VM DA neurons from pluripotent stem cell-derived neural cell populations......The main motor symptoms of Parkinson's disease are due to the loss of dopaminergic (DA) neurons in the ventral midbrain (VM). For the future treatment of Parkinson's disease with cell transplantation it is important to develop efficient differentiation methods for production of human iPSCs and h......ESCs-derived midbrain-type DA neurons. Here we describe an efficient differentiation and sorting strategy for DA neurons from both human ES/iPS cells and non-human primate iPSCs. The use of non-human primate iPSCs for neuronal differentiation and autologous transplantation is important for preclinical evaluation...

  16. Retinoic acid signalling is required for the efficient differentiation of CD4+ T cells into pathogenic effector cells during the development of intestinal inflammation

    DEFF Research Database (Denmark)

    Rivollier, Aymeric Marie Christian; Pool, Lieneke; Frising, Ulrika

    Epidemiological studies of vitamin A-deficient populations have illustrated the importance of the vitamin A metabolite retinoic acid (RA) in mucosal immune responses. However, RA seems to be a double-edge sword in CD4+ T cell biology. While it sustains the development of foxp3+ regulatory T cells......, it was also very recently reported to be essential for the stability of the Th1 lineage and to prevent transition to a Th17 program. Here we explored the role of RA signalling in CD4+ T cells during the development of intestinal inflammation in the T cell transfer colitis model. We found that RA signalling......-deficient CD4+ T cells are less potent at inducing intestinal inflammation compared to their RA signalling-competent counterparts and exhibit a differentiation skewing towards more IFNγ- IL-17+, IL-17+IFNγ+ and foxp3+ cells, while their capacity to differentiate into IL-17-IFNγ+ Th1 cells is compromised...

  17. The Heliospheric Termination Shock

    Science.gov (United States)

    Jokipii, J. R.

    2013-06-01

    The heliospheric termination shock is a vast, spheroidal shock wave marking the transition from the supersonic solar wind to the slower flow in the heliosheath, in response to the pressure of the interstellar medium. It is one of the most-important boundaries in the outer heliosphere. It affects energetic particles strongly and for this reason is a significant factor in the effects of the Sun on Galactic cosmic rays. This paper summarizes the general properties and overall large-scale structure and motions of the termination shock. Observations over the past several years, both in situ and remote, have dramatically revised our understanding of the shock. The consensus now is that the shock is quite blunt, is with the front, blunt side canted at an angle to the flow direction of the local interstellar plasma relative to the Sun, and is dynamical and turbulent. Much of this new understanding has come from remote observations of energetic charged particles interacting with the shock, radio waves and radiation backscattered from interstellar neutral atoms. The observations and the implications are discussed.

  18. Storage Space Allocation of Inbound Container in Railway Container Terminal

    Directory of Open Access Journals (Sweden)

    Li Wang

    2014-01-01

    Full Text Available Efficient storage strategy of railway container terminals is important in balancing resource utilization, reducing waiting time, and improving handling efficiency. In this paper, we consider the formulation and solution algorithm for storage space allocation problem of inbound containers in railway container terminal. The problem is formulated as two-stage optimization models, whose objectives are balancing the workload of inbound containers and reducing the overlapping amounts. An algorithm implement process based on rolling horizon approach is designed to solve the proposed models. Computational experiments on an actual railway container terminal show that the proposed approach is effective to solve space allocation problem of inbound container and is significant for the operation and organization of railway container terminals.

  19. Resolution and termination

    Directory of Open Access Journals (Sweden)

    Adina FOLTIŞ

    2012-01-01

    Full Text Available The resolution, the termination and the reduction of labour conscription are regulated by articles 1549-1554 in the new Civil Code, which represents the common law in this matter. We appreciate that the new regulation does not conclusively clarify the issue related to whether the existence of liability in order to call upon the resolution is necessary or not, because the existence of this condition has been inferred under the previous regulation from the fact that the absence of liability shifts the inexecution issue on the domain of fortuitous impossibility of execution, situation in which the resolution of the contract is not in question, but that of the risk it implies.

  20. Mobile Termination and Mobile Penetration

    OpenAIRE

    Hurkens, Sjaak; Jeon, Doh-Shin

    2009-01-01

    In this paper, we study how access pricing affects network competition when subscription demand is elastic and each network uses non-linear prices and can apply termination-based price discrimination. In the case of a fixed per minute termination charge, we find that a reduction of the termination charge below cost has two oppos- ing effects: it softens competition but helps to internalize network externalities. The former reduces mobile penetration while the latter boosts it. We find that fi...

  1. Mobile termination and mobile penetration

    OpenAIRE

    Hurkens, Sjaak

    2009-01-01

    In this paper, we study how access pricing affects network competition when subscription demand is elastic and each network uses non-linear prices and can apply termination-based price discrimination. In the case of a fixed per minute termination charge, we find that a reduction of the termination charge below cost has two opposing effects: it softens competition but helps to internalize network externalities. The former reduces mobile penetration while the latter boosts it. We find that firm...

  2. The Stigma of Dying: Attitudes Toward the Terminally Ill

    Science.gov (United States)

    Epley, Rita J.; McCaghy, Charles H.

    1978-01-01

    Using a range of semantic differential adjectives, 233 college students indicated attitudes toward young and old people who were healthy, ill, or terminally ill. Attitudes toward each state of health category separate into three factors: attitudes toward healthy, ill, and dying persons. (Author)

  3. Differential Impact of Plasma Proteins on the Adhesion Efficiency of Vascular-Targeted Carriers (VTCs) in Blood of Common Laboratory Animals.

    Science.gov (United States)

    Namdee, Katawut; Sobczynski, Daniel J; Onyskiw, Peter J; Eniola-Adefeso, Omolola

    2015-12-16

    Vascular-targeted carrier (VTC) interaction with human plasma is known to reduce targeted adhesion efficiency in vitro. However, the role of plasma proteins on the adhesion efficiency of VTCs in laboratory animals remains unknown. Here, in vitro blood flow assays are used to explore the effects of plasma from mouse, rabbit, and porcine on VTC adhesion. Porcine blood exhibited a strong negative plasma effect on VTC adhesion while no significant plasma effect was found with rabbit and mouse blood. A brush density poly(ethylene glycol) (PEG) on VTCs was effective at improving adhesion of microsized, but not nanosized, VTCs in porcine blood. Overall, the results suggest that porcine models, as opposed to mouse, can serve as better models in preclinical research for predicting the in vivo functionality of VTCs for use in humans. These considerations hold great importance for the design of various pharmaceutical products and development of reliable drug delivery systems.

  4. Testing the Semi-Strong Form efficiency to differentiate stock returns between Islamic and Non-Islamic firms: Empirical evidence using dividend announcement from Malaysia.

    OpenAIRE

    Saya, Muhammad Mujtuba

    2015-01-01

    This dissertation conducts an event study in the specific area of Efficient Market Hypothesis (EMH). It concentrates on the semi-strong form and focuses on exploring the impact of dividend announcements on share prices’ of Malaysian stock market (Bursa Malaysia). Further, it commences a comparison of Islamic (Shariah) compliant stocks and non-Islamic compliant stocks. A sample of 60 companies (30 Shariah and 30 Non-Shraiah compliant) were selected from the main board of Bursa Malaysia. An eve...

  5. [Diagnostic efficiency of decline rate of signal intensity and apparent diffusion coefficient with different b values for differentiating benign and malignant breast lesions on diffusion-weighted 3.0T magnetic resonance imaging].

    Science.gov (United States)

    Jiang, Jing; Liu, Wanhua; Ye, Yuanyuan; Wang, Rui; Li, Fengfang; Peng, Chengyu

    2014-06-17

    To investigate the diagnostic efficiency of decline rate of signal intensity and apparent diffusion coefficient with different b values for differentiating benign and malignant breast lesions on diffusion-weighted 3.0 T magnetic resonance imaging. A total of 152 patients with 162 confirmed histopathologically breast lesions (85 malignant and 77 benign) underwent 3.0 T diffusion-weighted magnetic resonance imaging. Four b values (0, 400, 800 and 1 000 s/mm²) were used. The signal intensity and ADC values of breast lesions were measured respectively. The signal intensity decline rate (SIDR) and apparent diffusion coefficient decline rate (ADCDR) were calculated respectively. SIDR = (signal intensity of lesions with low b value-signal intensity of lesions with high b value)/signal intensity of lesions with low b value, ADCDR = (ADC value of lesions with low b value-ADC value of lesions with high b value) /ADC value of lesions with low b value. The independent sample t-test was employed for statistical analyses and the receiver operating characteristic (ROC) curve for evaluating the diagnosis efficiency of SIDR and ADCDR values. Significant differences were observed in SIDR between benign and malignant breast lesions with b values of 0-400, 400-800 and 800-1 000 s/mm². The sensitivities of SIDR for differentiating benign and malignant breast lesions were 61.2%, 68.2% and 67.1%, the specificities 74.0%, 85.7% and 67.5%, the diagnosis accordance rates 67.3%, 76.5% and 67.3%, the positive predictive values 72.2%, 84.1% and 69.5% and the negative predictive values 63.3%, 71.0% and 65.0% respectively. Significant differences were observed in ADCDR between benign and malignant breast lesions with b values of 400-800 s/mm² and 800-1 000 s/mm². The sensitivities of SDR for differentiating benign and malignant breast lesions were 80.0% and 65.9%, the specificities 72.7% and 65.0%, the diagnostic accordance rates 76.5% and 65.4%, the positive predictive values 76.4% and 67

  6. Human Serum is as Efficient as Fetal Bovine Serum in Supporting Proliferation and Differentiation of Human Multipotent Stromal (Mesenchymal) Stem Cells In Vitro and In Vivo

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Haack-Sørensen, Mandana; Al-Nbaheen, May

    2011-01-01

    BACKGROUND: Human multipotent stromal (skeletal, mesenchymal) stem cells (hMSC) are employed in an increasing number of clinical trials for tissue regeneration of age-related degenerative diseases. However, routine use of fetal bovine sera (FBS) for their in vitro expansion is not optimal and may......) or adipocytic markers (PPAR-gamma2, lipoprotein lipase (LPL), aP2), respectively. In order to test for the functional capacity of hMSC-TERT that have been maintained in long-term cultures in the presence of HuS vs. FBS, the cells were mixed with hydroxyapatite/tricalcium phosphate (HA/TCP) and implanted...... subcutaneously in immune deficient mice. hMSC maintained in HuS vs. FBS formed comparable heterotopic bone. DISCUSSION: Human serum can support proliferation and differentiation of hMSC in vitro and can maintain their bone forming capacity in vivo. The use of human serum in cell cultures of hMSC intended...

  7. Efficient Power Scheduling in Smart Homes Using Hybrid Grey Wolf Differential Evolution Optimization Technique with Real Time and Critical Peak Pricing Schemes

    Directory of Open Access Journals (Sweden)

    Muqaddas Naz

    2018-02-01

    Full Text Available With the emergence of automated environments, energy demand by consumers is increasing rapidly. More than 80% of total electricity is being consumed in the residential sector. This brings a challenging task of maintaining the balance between demand and generation of electric power. In order to meet such challenges, a traditional grid is renovated by integrating two-way communication between the consumer and generation unit. To reduce electricity cost and peak load demand, demand side management (DSM is modeled as an optimization problem, and the solution is obtained by applying meta-heuristic techniques with different pricing schemes. In this paper, an optimization technique, the hybrid gray wolf differential evolution (HGWDE, is proposed by merging enhanced differential evolution (EDE and gray wolf optimization (GWO scheme using real-time pricing (RTP and critical peak pricing (CPP. Load shifting is performed from on-peak hours to off-peak hours depending on the electricity cost defined by the utility. However, there is a trade-off between user comfort and cost. To validate the performance of the proposed algorithm, simulations have been carried out in MATLAB. Results illustrate that using RTP, the peak to average ratio (PAR is reduced to 53.02%, 29.02% and 26.55%, while the electricity bill is reduced to 12.81%, 12.012% and 12.95%, respectively, for the 15-, 30- and 60-min operational time interval (OTI. On the other hand, the PAR and electricity bill are reduced to 47.27%, 22.91%, 22% and 13.04%, 12%, 11.11% using the CPP tariff.

  8. Termination of DNA replication forks: "Breaking up is hard to do".

    Science.gov (United States)

    Bailey, Rachael; Priego Moreno, Sara; Gambus, Agnieszka

    2015-01-01

    To ensure duplication of the entire genome, eukaryotic DNA replication initiates from thousands of replication origins. The replication forks move through the chromatin until they encounter forks from neighboring origins. During replication fork termination forks converge, the replisomes disassemble and topoisomerase II resolves the daughter DNA molecules. If not resolved efficiently, terminating forks result in genomic instability through the formation of pathogenic structures. Our recent findings shed light onto the mechanism of replisome disassembly upon replication fork termination. We have shown that termination-specific polyubiquitylation of the replicative helicase component - Mcm7, leads to dissolution of the active helicase in a process dependent on the p97/VCP/Cdc48 segregase. The inhibition of terminating helicase disassembly resulted in a replication termination defect. In this extended view we present hypothetical models of replication fork termination and discuss remaining and emerging questions in the DNA replication termination field.

  9. Selection of Air Terminal Device

    DEFF Research Database (Denmark)

    Nielsen, Peter V.

    This paper discusses the selection of the air terminal device for the experiments and numerical prediction in the International Energy Agency Annex 20 work: Air Flow Pattern within Buildings,......This paper discusses the selection of the air terminal device for the experiments and numerical prediction in the International Energy Agency Annex 20 work: Air Flow Pattern within Buildings,...

  10. The practice of terminal discharge.

    Science.gov (United States)

    Radha Krishna, Lalit Kumar; Murugam, Vengadasalam; Quah, Daniel Song Chiek

    2017-01-01

    'Terminal discharges' are carried out in Singapore for patients who wish to die at home. However, if due diligence is not exercised, parallels may be drawn with euthanasia. We present a theoretical discussion beginning with the definition of terminal discharges and the reasons why they are carried out in Singapore. By considering the intention behind terminal discharges and utilising a multidisciplinary team to deliberate on the clinical, social and ethical intricacies with a patient- and context-specific approach, euthanasia is avoided. It is hoped that this will provide a platform for professionals in palliative medicine to negotiate challenging issues when arranging a terminal discharge, so as to avoid the pitfall of committing euthanasia in a country such as Singapore where euthanasia is illegal. It is hoped that a set of guidelines for terminal discharges may someday be realised to assist professionals in Singapore and around the world.

  11. Improving thermal efficiency and increasing production rate in the double moving beds thermally coupled reactors by using differential evolution (DE) technique

    International Nuclear Information System (INIS)

    Karimi, Mohsen; Rahimpour, Mohammad Reza; Rafiei, Razieh; Shariati, Alireza; Iranshahi, Davood

    2016-01-01

    Highlights: • Double moving bed thermally coupled reactor is modeled in two dimensions. • The required heat of naphtha process is attained with nitrobenzene hydrogenation. • DE optimization method is applied to optimize operating conditions. • Hydrogen, aromatic and aniline productions increase in the proposed configuration. - Abstract: According to the global requirements for energy saving and the control of global warming, multifunctional auto-thermal reactors as a novel concept in the process integration (PI) have risen up in the recent years. In the novel modification presented in this study, the required heat of endothermic naphtha reforming process has been supplied by nitrobenzene hydrogenation reaction. In addition, the enhancement of reactor performance, such as the increase of production rate, has become a key issue in the diverse industries. Thus, Differential Evolution (DE) technique is applied to optimize the operating conditions (temperature and pressure) and designing parameters of a thermally coupled reactor with double moving beds. Ultimately, the obtained results of the proposed model are compared with non-optimized and conventional model. This model results in noticeable reduction in the operational costs as well as enhancement of the net profit of the plant. The increase in the hydrogen and aromatic production shows the superiority of the proposed model.

  12. Planning of Terminal Construction at the Port of Ploce

    Directory of Open Access Journals (Sweden)

    Čedomir Dundović

    2007-07-01

    Full Text Available The paper presents a systematic and comprehensive analysisof both the technological justification for the constructionof a container/multi-purpose terminal and a dry bulk terminal,and the efficiency of loading/unloading facilities. The organisationof Croatian ports is inefficient and the technology usedin outdated. Traffic links with the mainland, the continent andthe world are unsatisfactory, with traffic infrastructure impactingadversely on operational efficiency. Analysis results of thepresent condition of port traffic and the influence of traffic onport operations and development indicate that the Port ofPlace lacks a multi-purpose terminal that would enable modemcontainer traffic. Because of the inefficient cargo-handlingprocedure and manner of storing bulk cargo in the Port ofPlace, it is necessary to plan the construction of a coal andiron ore terminal taking into account spatia~ technological,economic and ecological development factors. The authorsalso examine the importance of regional initiatives spurringthe development of Croatia and, in particular, the port systemas part of the EU's Pan-European transport corridor V BranchC. Research results are presented by a traffic and technologicaldesign for a container/multi-purpose terminal and dry bulkterminal capable of providing an appropriate level of servicefor all terminal users.

  13. Genetic differentiation and forensic efficiency evaluation for Chinese Salar ethnic minority based on a 5-dye multiplex insertion and deletion panel.

    Science.gov (United States)

    Ma, Ruilin; Shen, Chunmei; Wei, Yuanyuan; Jin, Xiaoye; Guo, Yuxin; Mu, Yuling; Sun, Siqi; Chen, Chong; Cui, Wei; Wei, Zhaoming; Lian, Zhenmin

    2018-06-20

    The present study investigated the genetic diversities of 30 autosomal insertion and deletion (InDel) loci of Investigator DIPplex kit (Qiagen) in Chinese Salar ethnic minority and explored the genetic relationships between the studied Salar group and other populations. The allelic frequencies of deletion alleles at the 30 InDel loci were in the range of 0.1739 (HLD64) to 0.8478 (HLD39). The discrimination power, polymorphism information content and probability of exclusion ranged from 0.4101 (HLD39) to 0.6447 (HLD136), 0.2247 (HLD39) to 0.3750 (HLD92) and 0.0400 (HLD39) to 0.2806 (HLD92), respectively. The observed and expected heterozygosity were in the range of 0.2348 (HLD39) to 0.5913 (HLD92), and 0.2580 (HLD39) to 0.5000 (HLD92), respectively. The cumulative discrimination power and probability of exclusion of the 30 loci reached 0.999999999993418 and 0.99039, respectively. The results of population genetic differentiation comparisons revealed that Salar group had similar allele distributions with Qinghai Tibetan, Xibe and Yi groups. Population Bayesian cluster analysis showed that there were similar ancestry components between Salar group and most Chinese populations. Besides, the principal components analysis and phylogenetic reconstructions further indicated that Salar group had intimate genetic relationships with Qinghai Tibetan and Xibe groups. In short, the results of the current studies indicated the genetic distributions of the 30 InDel loci in Salar group were relatively high genetic polymorphisms, which could be used in forensic individual identifications and as a supplementary tool for complex paternity testing. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Incorporating pTGF-β1/calcium phosphate nanoparticles with fibronectin into 3-dimensional collagen/chitosan scaffolds: Efficient, sustained gene delivery to stem cells for chondrogenic differentiation

    Directory of Open Access Journals (Sweden)

    X Cao

    2012-02-01

    Full Text Available The objective of this study was to prepare a 3-dimensional nanoparticle gene delivery system (3D-NGDS based on collagen/chitosan scaffolds, in which plasmid transforming growth factor beta 1 (TGF-β1/calcium phosphate nanoparticles mixed with fibronectin (FN were used to transfect mesenchymal stem cells (MSCs. Scanning electron microscopy was used to characterise the microstructure of 3-dimensional collagen/chitosan scaffolds. An analysis performed to quantify the TGF-b1 concentrations in MSC cultures revealed that the MSCs transfected with the 3D-NGDS showed remarkably high levels of TGF-b1 over long periods, retaining a concentration of TGF-b1 of approximately 10 ng/mL within two weeks, with the highest level (12.6 ng/mL being observed on the 6th day. An immunohistochemistry analysis for collagen type II revealed that much higher production of collagen II from the 9th to 15th day was observed in the 3D-NGDS-transfected MSCs than that in MSCs transfected by the Lipofectamine 2000 method. The glycosaminoglycan content of the 3D-NGDS was comparable to those treated with TGF-β1 as well as TGF-β1 plus dexamethasone, and was significantly higher than those treated with free plasmid and Lipofectamine 2000. A remarkable type I collagen expression inhibition of the 3D-NGDS at day 21 was observed via ELISA. These results suggested that transfection with the 3D-NGDS could successfully induce MSC chondrogenic differentiation in vitro without dexamethasone. In summary, the 3D-NGDS could be developed into a promising alternative method to transfer exogenous nucleic acid to MSCs in clinical trials.

  15. Osteogenic cell differentiation on H-terminated and O-terminated nanocrystalline diamond films

    Czech Academy of Sciences Publication Activity Database

    Lišková, Jana; Babchenko, Oleg; Varga, Marián; Kromka, Alexander; Hadraba, Daniel; Švindrych, Zdeněk; Burdíková, Zuzana; Bačáková, Lucie

    2015-01-01

    Roč. 10, č. 2015 (2015), s. 869-884 E-ISSN 1178-2013 R&D Projects: GA MŠk(CZ) EE2.3.30.0025; GA ČR(CZ) GBP108/12/G108 Institutional support: RVO:67985823 ; RVO:68378271 Keywords : nanocrystalline diamond film * osteoblast * Saos-2 Subject RIV: EI - Biotechnology ; Bionics Impact factor: 4.320, year: 2015

  16. Ports and Terminals : Planning and Functional Design

    NARCIS (Netherlands)

    Groenveld, R.; Velsink, H.

    1993-01-01

    1. Maritime transport, means and commodities 3. Principles of integrated port planning 4. Planning and design of a port's water areas 5. Port terminals - introduction 6. Conventional general cargo terminals 7. Container terminals 8. Oil & liquid gas terminals 9. Dry bulk cargo terminals 10. Fishery

  17. Assessing Port Governance, Devolution and Terminal Performance in Nigeria

    Directory of Open Access Journals (Sweden)

    D. E. Onwuegbuchunam

    2018-02-01

    Full Text Available Concerns about performance and efficiency in port terminals led many national governments to embark on port reforms. The Federal government of Nigeria, for example, adopted the Landlord port model which brought about concessioning of port terminals to private operators. Despite high investments in terminal facilities by the private terminal operators, there are still complaints about level of service offered to port users. This paper applied key performance indicator metrics and parameters of queuing model in assessing performance of Nigeria’s concessioned port terminals. Data for the study were obtained from terminal level records of cargo and ship handling activities for years 2000 to 2015. Major findings indicate that cargo and vessel throughputs improved after the reforms in the six ports examined. However, much variability was observed in trends in ships’ turnround times across all ports after the concession policy implementation. Additional results from the queuing model analysis suggest that the high ships turnround times observed in some ports are associated to delays in ship operation at the berths. The paper recommends that policy interventions be focused on ship operations at the berths as a step in improving service level in the port terminals.

  18. Two-terminal video coding.

    Science.gov (United States)

    Yang, Yang; Stanković, Vladimir; Xiong, Zixiang; Zhao, Wei

    2009-03-01

    Following recent works on the rate region of the quadratic Gaussian two-terminal source coding problem and limit-approaching code designs, this paper examines multiterminal source coding of two correlated, i.e., stereo, video sequences to save the sum rate over independent coding of both sequences. Two multiterminal video coding schemes are proposed. In the first scheme, the left sequence of the stereo pair is coded by H.264/AVC and used at the joint decoder to facilitate Wyner-Ziv coding of the right video sequence. The first I-frame of the right sequence is successively coded by H.264/AVC Intracoding and Wyner-Ziv coding. An efficient stereo matching algorithm based on loopy belief propagation is then adopted at the decoder to produce pixel-level disparity maps between the corresponding frames of the two decoded video sequences on the fly. Based on the disparity maps, side information for both motion vectors and motion-compensated residual frames of the right sequence are generated at the decoder before Wyner-Ziv encoding. In the second scheme, source splitting is employed on top of classic and Wyner-Ziv coding for compression of both I-frames to allow flexible rate allocation between the two sequences. Experiments with both schemes on stereo video sequences using H.264/AVC, LDPC codes for Slepian-Wolf coding of the motion vectors, and scalar quantization in conjunction with LDPC codes for Wyner-Ziv coding of the residual coefficients give a slightly lower sum rate than separate H.264/AVC coding of both sequences at the same video quality.

  19. Power Efficient Design of DisplayPort (7.0) Using Low-voltage differential signaling IO Standard Via UltraScale Field Programming Gate Arrays

    DEFF Research Database (Denmark)

    Das, Bhagwan; Abdullah, M.F.L.; Hussain, Dil muhammed Akbar

    2017-01-01

    Port (7.0) need be reduced. In this paper, a power efficient design for DisplayPort (7.0) is proposed using LVDS IO Standard. The proposed design is tested for different frequencies; 500 MHz, 700 MHz, 1.0 GHz, and 1.6 GHz. The design is implemented using vhdl in UltraScale FPGA. It is determined...... the designed vhdl based design of DisplayPort (7.0) can reduced 92% using LVDS IO Standard for all frequencies; 500 MHz, 700 MHz, 1.0 GHz, and 1.6 GHz, compared to vhdl based design of DisplayPort (7.0) without using IO Standard. The proposed design of vhdl based design of DisplayPort (7.0) using LVDS IO...... Standard offers no power consumption for DisplayPort (7.0) in standby mode. The vhdl based design of DisplayPort (7.0) using LVDS IO Standard will be helpful to process the high resolution video at low power consumption....

  20. Efficient Synthesis of Differentiated syn-1,2-Diol Derivatives by Asymmetric Transfer Hydrogenation-Dynamic Kinetic Resolution of α-Alkoxy-Substituted β-Ketoesters.

    Science.gov (United States)

    Monnereau, Laure; Cartigny, Damien; Scalone, Michelangelo; Ayad, Tahar; Ratovelomanana-Vidal, Virginie

    2015-08-10

    Asymmetric transfer hydrogenation was applied to a wide range of racemic aryl α-alkoxy-β-ketoesters in the presence of well-defined, commercially available, chiral catalyst Ru(II) -(N-p-toluenesulfonyl-1,2-diphenylethylenediamine) and a 5:2 mixture of formic acid and triethylamine as the hydrogen source. Under these conditions, dynamic kinetic resolution was efficiently promoted to provide the corresponding syn α-alkoxy-β-hydroxyesters derived from substituted aromatic and heteroaromatic aldehydes with a high level of diastereoselectivity (diastereomeric ratio (d.r.)>99:1) and an almost perfect enantioselectivity (enantiomeric excess (ee)>99 %). Additionally, after extensive screening of the reaction conditions, the use of Ru(II) - and Rh(III) -tethered precatalysts extended this process to more-challenging substrates that bore alkenyl-, alkynyl-, and alkyl substituents to provide the corresponding syn α-alkoxy-β-hydroxyesters with excellent enantiocontrol (up to 99 % ee) and good to perfect diastereocontrol (d.r.>99:1). Lastly, the synthetic utility of the present protocol was demonstrated by application to the asymmetric synthesis of chiral ester ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)-propanoate, which is an important pharmacophore in a number of peroxisome proliferator-activated receptor α/γ dual agonist advanced drug candidates used for the treatment of type-II diabetes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.