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Sample records for enhances cell adaptation

  1. Molecular mechanism of radioadaptive response: A cross-adaptive response for enhanced repair of DNA damage in adapted cells

    International Nuclear Information System (INIS)

    Takaji Ikushima

    1997-01-01

    The radioadaptive response (RAR) has been attributed to the induction of a repair mechanism by low doses of ionizing radiation, but the molecular nature of the mechanism is not yet elucidated. We have characterized RAR in a series of experiments in cultured Chinese hamster V79 cells. A 4-h interval is required for the full expression of RAR, which decays with the progression of cell proliferation. Treatments with inhibitors of poly(ADP-ribose) polymerase, protein- or RNA synthesis, and protein kinase C suppress the RAR expression. The RAR cross-reacts on clastogenic lesions induced by other physical and chemical DNA-damaging agents. The presence of newly synthesised proteins has been detected during the expression period. Experiments performed using single-cell gel electrophoresis provided more direct evidence for a faster and enhaced DNA repair rate in adapted cells. Here, using single-cell gel electrophoresis, a cross-adaptive response has been demonstrated for enhanced repair of DNA damage induced by neocarzinostatin in radio-adapted cells. (author)

  2. Enhanced attention amplifies face adaptation.

    Science.gov (United States)

    Rhodes, Gillian; Jeffery, Linda; Evangelista, Emma; Ewing, Louise; Peters, Marianne; Taylor, Libby

    2011-08-15

    Perceptual adaptation not only produces striking perceptual aftereffects, but also enhances coding efficiency and discrimination by calibrating coding mechanisms to prevailing inputs. Attention to simple stimuli increases adaptation, potentially enhancing its functional benefits. Here we show that attention also increases adaptation to faces. In Experiment 1, face identity aftereffects increased when attention to adapting faces was increased using a change detection task. In Experiment 2, figural (distortion) face aftereffects increased when attention was increased using a snap game (detecting immediate repeats) during adaptation. Both were large effects. Contributions of low-level adaptation were reduced using free viewing (both experiments) and a size change between adapt and test faces (Experiment 2). We suggest that attention may enhance adaptation throughout the entire cortical visual pathway, with functional benefits well beyond the immediate advantages of selective processing of potentially important stimuli. These results highlight the potential to facilitate adaptive updating of face-coding mechanisms by strategic deployment of attentional resources. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Countermeasures to Enhance Sensorimotor Adaptability

    Science.gov (United States)

    Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Brady, R. A.; Batson, C. C.; Miller, C. A.; Cohen, H. S.

    2011-01-01

    During exploration-class missions, sensorimotor disturbances may lead to disruption in the ability to ambulate and perform functional tasks during the initial introduction to a novel gravitational environment following a landing on a planetary surface. The goal of our current project is to develop a sensorimotor adaptability (SA) training program to facilitate rapid adaptation to novel gravitational environments. We have developed a unique training system comprised of a treadmill placed on a motion-base facing a virtual visual scene that provides an unstable walking surface combined with incongruent visual flow designed to enhance sensorimotor adaptability. We have conducted a series of studies that have shown: Training using a combination of modified visual flow and support surface motion during treadmill walking enhances locomotor adaptability to a novel sensorimotor environment. Trained individuals become more proficient at performing multiple competing tasks while walking during adaptation to novel discordant sensorimotor conditions. Trained subjects can retain their increased level of adaptability over a six months period. SA training is effective in producing increased adaptability in a more complex over-ground ambulatory task on an obstacle course. This confirms that for a complex task like walking, treadmill training contains enough of the critical features of overground walking to be an effective training modality. The structure of individual training sessions can be optimized to promote fast/strategic motor learning. Training sessions that each contain short-duration exposures to multiple perturbation stimuli allows subjects to acquire a greater ability to rapidly reorganize appropriate response strategies when encountering a novel sensory environment. Individual sensory biases (i.e. increased visual dependency) can predict adaptive responses to novel sensory environments suggesting that customized training prescriptions can be developed to enhance

  4. Autophagy Enhances the Aggressiveness of Human Colorectal Cancer Cells and Their Ability to Adapt to Apoptotic Stimulus

    International Nuclear Information System (INIS)

    Zheng, Hai-yang; Zhang, Xiao-yang; Wang, Xing-fen; Sun, Bao-cun

    2012-01-01

    To investigate LC3B-II and active caspase-3 expression in human colorectal cancer to elucidate the role of autophagy, and to explore the relationship of autophagy with apoptosis in human colorectal cancer. LC3B expression was detected by immunohistochemistry in 53 human colorectal cancer tissues and 20 normal colon tissues. The protein levels of LC3B-II and active caspase-3 were also determined by Western blot analysis in 23 human colorectal cancer tissues and 10 normal colon tissues. LC3B was expressed both in cancer cells and normal epithelial cells. LC3B expression in the peripheral area of cancer tissues was correlated with several clinicopathological factors, including tumor differentiation (P=0.002), growth pattern of the tumor margin (P=0.028), pN (P=0.002), pStage (P=0.032), as well as vessel and nerve plexus invasion (P=0.002). The protein level of LC3B-II in cancer tissue was significantly higher than in normal tissue (P=0.038), but the expression of active forms of procaspase-3 in cancer tissue was lower (P=0.041). There was a statistically significant positive correlation between the expression levels of LC3B-II and the active forms of procaspase-3 (r=0.537, P=0.008). Autophagy has a prosurvival role in human colorectal cancer. Autophagy enhances the aggressiveness of colorectal cancer cells and their ability to adapt to apoptotic stimulus

  5. Inducible protective processes in animal systems XV: Hyperthermia enhances the Ethyl methanesulfonate induced adaptive response in meiotic cells of grasshopper Poecilocerus pictus

    Directory of Open Access Journals (Sweden)

    R. Venu

    2016-04-01

    Conclusion: There is a protection against EMS induced anomalies by hyperthermia in in vivo P. pictus. As far as our knowledge is concerned, this is the first report to demonstrate that hyperthermia enhances the EMS induced adaptive response in in vivo meiotic cells.

  6. Adapted physical exercise enhances activation and differentiation potential of satellite cells in the skeletal muscle of old mice.

    Science.gov (United States)

    Cisterna, Barbara; Giagnacovo, Marzia; Costanzo, Manuela; Fattoretti, Patrizia; Zancanaro, Carlo; Pellicciari, Carlo; Malatesta, Manuela

    2016-05-01

    During ageing, a progressive loss of skeletal muscle mass and a decrease in muscle strength and endurance take place, in the condition termed sarcopenia. The mechanisms of sarcopenia are complex and still unclear; however, it is known that muscle atrophy is associated with a decline in the number and/or efficiency of satellite cells, the main contributors to muscle regeneration. Physical exercise proved beneficial in sarcopenia; however, knowledge of the effect of adapted physical exercise on the myogenic properties of satellite cells in aged muscles is limited. In this study the amount and activation state of satellite cells as well as their proliferation and differentiation potential were assessed in situ by morphology, morphometry and immunocytochemistry at light and transmission electron microscopy on 28-month-old mice submitted to adapted aerobic physical exercise on a treadmill. Sedentary age-matched mice served as controls, and sedentary adult mice were used as a reference for an unperturbed control at an age when the capability of muscle regeneration is still high. The effect of physical exercise in aged muscles was further analysed by comparing the myogenic potential of satellite cells isolated from old running and old sedentary mice using an in vitro system that allows observation of the differentiation process under controlled experimental conditions. The results of this ex vivo and in vitro study demonstrated that adapted physical exercise increases the number and activation of satellite cells as well as their capability to differentiate into structurally and functionally correct myotubes (even though the age-related impairment in myotube formation is not fully reversed): this evidence further supports adapted physical exercise as a powerful, non-pharmacological approach to counteract sarcopenia and the age-related deterioration of satellite cell capabilities even at very advanced age. © 2016 Anatomical Society.

  7. Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition.

    Directory of Open Access Journals (Sweden)

    Sarah L Sherrington

    2017-05-01

    Full Text Available Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this "unmasking" of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection.

  8. Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition

    Science.gov (United States)

    Sorsby, Eleanor; Mahtey, Nabeel; Brown, Ian

    2017-01-01

    Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this “unmasking” of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection. PMID:28542528

  9. An automated approach for solution based mesh adaptation to enhance numerical accuracy for a given number of grid cells

    NARCIS (Netherlands)

    Lucas, P.; Van Zuijlen, A.H.; Bijl, H.

    2009-01-01

    Mesh adaptation is a fairly established tool to obtain numerically accurate solutions for flow problems. Computational efficiency is, however, not always guaranteed for the adaptation strategies found in literature. Typically excessive mesh growth diminishes the potential efficiency gain. This

  10. VSVΔG/EBOV GP-induced innate protection enhances natural killer cell activity to increase survival in a lethal mouse adapted Ebola virus infection.

    Science.gov (United States)

    Williams, Kinola J N; Qiu, Xiangguo; Fernando, Lisa; Jones, Steven M; Alimonti, Judie B

    2015-02-01

    Members of the species Zaire ebolavirus cause severe hemorrhagic fever with up to a 90% mortality rate in humans. The VSVΔG/EBOV GP vaccine has provided 100% protection in the mouse, guinea pig, and nonhuman primate (NHP) models, and has also been utilized as a post-exposure therapeutic to protect mice, guinea pigs, and NHPs from a lethal challenge of Ebola virus (EBOV). EBOV infection causes rapid mortality in human and animal models, with death occurring as early as 6 days after infection, suggesting a vital role for the innate immune system to control the infection before cells of the adaptive immune system can assume control. Natural killer (NK) cells are the predominant cell of the innate immune response, which has been shown to expand with VSVΔG/EBOV GP treatment. In the current study, an in vivo mouse model of the VSVΔG/EBOV GP post-exposure treatment was used for a mouse adapted (MA)-EBOV infection, to determine the putative VSVΔG/EBOV GP-induced protective mechanism of NK cells. NK depletion studies demonstrated that mice with NK cells survive longer in a MA-EBOV infection, which is further enhanced with VSVΔG/EBOV GP treatment. NK cell mediated cytotoxicity and IFN-γ secretion was significantly higher with VSVΔG/EBOV GP treatment. Cell mediated cytotoxicity assays and perforin knockout mice experiments suggest that there are perforin-dependent and -independent mechanisms involved. Together, these data suggest that NK cells play an important role in VSVΔG/EBOV GP-induced protection of EBOV by increasing NK cytotoxicity, and IFN-γ secretion.

  11. Adaptive mutations enhance assembly and cell-to-cell transmission of a high-titer hepatitis C virus genotype 5a Core-NS2 JFH1-based recombinant

    DEFF Research Database (Denmark)

    Mathiesen, Christian K; Prentoe, Jannick; Meredith, Luke W

    2015-01-01

    UNLABELLED: Recombinant hepatitis C virus (HCV) clones propagated in human hepatoma cell cultures yield relatively low infectivity titers. Here, we adapted the JFH1-based Core-NS2 recombinant SA13/JFH1C3405G,A3696G (termed SA13/JFH1orig), of the poorly characterized genotype 5a, to Huh7.5 cells......-titer production of diverse HCV strains would be advantageous. Our study offers important functional data on how cell culture-adaptive mutations identified in genotype 5a JFH1-based HCVcc permit high-titer culture by affecting HCV genesis through increasing virus assembly and HCV fitness by enhancing the virus...... specific infectivity and cell-to-cell transmission ability, without influencing the biophysical particle properties. High-titer HCVcc like the one described in this study may be pivotal in future vaccine-related studies where large quantities of infectious HCV particles are necessary....

  12. Enhancing Brigade Combat Team Adaptability

    Science.gov (United States)

    2010-06-11

    Developing Learning Infrastructures (Training, Education , Practice, Research, Doctrine) -Create a shared vision -Build the business case (assess/Buy...To effectively respond to the characteristics of the operational environment, Brigade Combat Teams must be able to learn constantly from experience...behavior. Organizational adaptive behavior consists of three supporting emergent behaviors which are: self-organization, learning , and organizational

  13. Mansonella perstans microfilaremic individuals are characterized by enhanced type 2 helper T and regulatory T and B cell subsets and dampened systemic innate and adaptive immune responses.

    Directory of Open Access Journals (Sweden)

    Manuel Ritter

    2018-01-01

    Full Text Available The filarial nematode Mansonella perstans is endemic throughout Africa, northern South America and the Caribbean. Interestingly, M. perstans-infected individuals present no distinct clinical picture associated with certain pathology. Due to its relatively silent nature, research on this tropical disease has been neglected, especially M. perstans-driven immune responses. A hindrance in obtaining data on M. perstans-specific responses has been the inability to obtain adult worms since their habitats in serous cavities are difficult to access. Thus, in this study, for the first time, we used Mansonella perstans worm antigen extract as stimulant to obtain filarial-specific recall and immunoglobulin responses from M. perstans microfilaremic individuals (Mp MF+ from Cameroon. Moreover, systemic immune profiles in sera and immune cell composition in peripheral blood from Mp MF+ and amicrofilaremic individuals (Mp MF- were obtained. Our data reveal that Mp MF+ individuals showed significantly reduced cytokine (IL-4, IL-6 and IL-12p70 and chemokine levels (IL-8 and RANTES, but significantly higher MIP-1β as well as increased M. perstans-specific IgG4 levels compared to Mp MF- individuals. In contrast, upon re-stimulation with worm antigen extract, IFN-γ, IL-13, IL-10 and IL-17A secretion was enhanced in cell cultures from Mp MF+ individuals when compared to those from cultures of healthy European individuals. Moreover, analysis of immune cell composition in peripheral blood from Mp MF+ individuals revealed increased type 2 helper T (Th2, natural killer (NK, regulatory B and T cell (Breg and Treg subsets but decreased type 1 regulatory T (Tr1 cells. In summary, this study deciphers for the first time, M. perstans-specific immune responses using worm antigen extract and shows that patent M. perstans infections have distinct Th2, Breg and Treg subsets accompanied with reduced systemic innate and adaptive immune responses and dominant filarial-specific Ig

  14. Enhancing astronaut performance using sensorimotor adaptability training

    OpenAIRE

    Bloomberg, Jacob J.; Peters, Brian T.; Cohen, Helen S.; Mulavara, Ajitkumar P.

    2015-01-01

    Astronauts experience disturbances in balance and gait function when they return to Earth. The highly plastic human brain enables individuals to modify their behavior to match the prevailing environment. Subjects participating in specially designed variable sensory challenge training programs can enhance their ability to rapidly adapt to novel sensory situations. This is useful in our application because we aim to train astronauts to rapidly formulate effective strategies to cope with the bal...

  15. Adaptive multiscale processing for contrast enhancement

    Science.gov (United States)

    Laine, Andrew F.; Song, Shuwu; Fan, Jian; Huda, Walter; Honeyman, Janice C.; Steinbach, Barbara G.

    1993-07-01

    This paper introduces a novel approach for accomplishing mammographic feature analysis through overcomplete multiresolution representations. We show that efficient representations may be identified from digital mammograms within a continuum of scale space and used to enhance features of importance to mammography. Choosing analyzing functions that are well localized in both space and frequency, results in a powerful methodology for image analysis. We describe methods of contrast enhancement based on two overcomplete (redundant) multiscale representations: (1) Dyadic wavelet transform (2) (phi) -transform. Mammograms are reconstructed from transform coefficients modified at one or more levels by non-linear, logarithmic and constant scale-space weight functions. Multiscale edges identified within distinct levels of transform space provide a local support for enhancement throughout each decomposition. We demonstrate that features extracted from wavelet spaces can provide an adaptive mechanism for accomplishing local contrast enhancement. We suggest that multiscale detection and local enhancement of singularities may be effectively employed for the visualization of breast pathology without excessive noise amplification.

  16. Enhancing Astronaut Performance using Sensorimotor Adaptability Training

    Directory of Open Access Journals (Sweden)

    Jacob J Bloomberg

    2015-09-01

    Full Text Available Astronauts experience disturbances in balance and gait function when they return to Earth. The highly plastic human brain enables individuals to modify their behavior to match the prevailing environment. Subjects participating in specially designed variable sensory challenge training programs can enhance their ability to rapidly adapt to novel sensory situations. This is useful in our application because we aim to train astronauts to rapidly formulate effective strategies to cope with the balance and locomotor challenges associated with new gravitational environments - enhancing their ability to learn to learn. We do this by coupling various combinations of sensorimotor challenges with treadmill walking. A unique training system has been developed that is comprised of a treadmill mounted on a motion base to produce movement of the support surface during walking. This system provides challenges to gait stability. Additional sensory variation and challenge are imposed with a virtual visual scene that presents subjects with various combinations of discordant visual information during treadmill walking. This experience allows them to practice resolving challenging and conflicting novel sensory information to improve their ability to adapt rapidly. Information obtained from this work will inform the design of the next generation of sensorimotor countermeasures for astronauts.

  17. Enhancing astronaut performance using sensorimotor adaptability training.

    Science.gov (United States)

    Bloomberg, Jacob J; Peters, Brian T; Cohen, Helen S; Mulavara, Ajitkumar P

    2015-01-01

    Astronauts experience disturbances in balance and gait function when they return to Earth. The highly plastic human brain enables individuals to modify their behavior to match the prevailing environment. Subjects participating in specially designed variable sensory challenge training programs can enhance their ability to rapidly adapt to novel sensory situations. This is useful in our application because we aim to train astronauts to rapidly formulate effective strategies to cope with the balance and locomotor challenges associated with new gravitational environments-enhancing their ability to "learn to learn." We do this by coupling various combinations of sensorimotor challenges with treadmill walking. A unique training system has been developed that is comprised of a treadmill mounted on a motion base to produce movement of the support surface during walking. This system provides challenges to gait stability. Additional sensory variation and challenge are imposed with a virtual visual scene that presents subjects with various combinations of discordant visual information during treadmill walking. This experience allows them to practice resolving challenging and conflicting novel sensory information to improve their ability to adapt rapidly. Information obtained from this work will inform the design of the next generation of sensorimotor countermeasures for astronauts.

  18. Local adaptive tone mapping for video enhancement

    Science.gov (United States)

    Lachine, Vladimir; Dai, Min (.

    2015-03-01

    As new technologies like High Dynamic Range cameras, AMOLED and high resolution displays emerge on consumer electronics market, it becomes very important to deliver the best picture quality for mobile devices. Tone Mapping (TM) is a popular technique to enhance visual quality. However, the traditional implementation of Tone Mapping procedure is limited by pixel's value to value mapping, and the performance is restricted in terms of local sharpness and colorfulness. To overcome the drawbacks of traditional TM, we propose a spatial-frequency based framework in this paper. In the proposed solution, intensity component of an input video/image signal is split on low pass filtered (LPF) and high pass filtered (HPF) bands. Tone Mapping (TM) function is applied to LPF band to improve the global contrast/brightness, and HPF band is added back afterwards to keep the local contrast. The HPF band may be adjusted by a coring function to avoid noise boosting and signal overshooting. Colorfulness of an original image may be preserved or enhanced by chroma components correction by means of saturation function. Localized content adaptation is further improved by dividing an image to a set of non-overlapped regions and modifying each region individually. The suggested framework allows users to implement a wide range of tone mapping applications with perceptional local sharpness and colorfulness preserved or enhanced. Corresponding hardware circuit may be integrated in camera, video or display pipeline with minimal hardware budget

  19. Cancer cell adaptation to chemotherapy

    International Nuclear Information System (INIS)

    Di Nicolantonio, Federica; Johnson, Penny; Somers, Shaw S; Toh, Simon; Higgins, Bernie; Lamont, Alan; Gulliford, Tim; Hurren, Jeremy; Yiangou, Constantinos; Cree, Ian A; Mercer, Stuart J; Knight, Louise A; Gabriel, Francis G; Whitehouse, Pauline A; Sharma, Sanjay; Fernando, Augusta; Glaysher, Sharon; Di Palma, Silvana

    2005-01-01

    Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors. Cells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days). Real-time quantitative PCR was used to measure up- or down-regulation of 16 different resistance/target genes, and when tissue was available, immunohistochemistry was used to assess the protein levels. In 8/16 paired esophageal biopsies, there was an increase in the expression of multi-drug resistance gene 1 (MDR1) following epirubicin + cisplatin + 5-fluorouracil (ECF) chemotherapy and this was accompanied by increased expression of the MDR-1 encoded protein, P-gp. Following exposure to doxorubicin in vitro, 13/14 breast carcinomas and 9/12 ovarian carcinomas showed >2-fold down-regulation of topoisomerase IIα (TOPOIIα). Exposure to topotecan in vitro, resulted in >4-fold down-regulation of TOPOIIα in 6/7 colorectal tumors and 8/10 ovarian tumors. This study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of response to the same drugs. Adaptation

  20. Germplasm enhancement for adaptation to climate changes

    Directory of Open Access Journals (Sweden)

    Marcelo J Carena

    2011-01-01

    Full Text Available Billions of dollars and crops are being lost to drying high moisture grain; drought, cold, and salt susceptibility; andto processing poor quality grain. Maize is a model crop for adaptation to climate changes. Breeding for adaptation is best doneunder challenging environmental conditions where strengths and weaknesses are quickly identified and most stable genotypes areselected. The North Dakota State University (NDSU maize breeding program is strategically located to develop products underextreme weather. It currently exploits northern U.S. environments that allow screening for adaptation traits that are as important asyield. The program focuses on germplasm adaptation and its integration into cultivar development, particularly those carryingunique alleles not present in the B73 and NAM genomes. There is a need for projects that are vital to agricultural research and willmeet present and future demands of superior genotypes tolerant to climate changes in the U.S. and abroad.

  1. Beta cell adaptation in pregnancy

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis

    2016-01-01

    Pregnancy is associated with a compensatory increase in beta cell mass. It is well established that somatolactogenic hormones contribute to the expansion both indirectly by their insulin antagonistic effects and directly by their mitogenic effects on the beta cells via receptors for prolactin...... and growth hormone expressed in rodent beta cells. However, the beta cell expansion in human pregnancy seems to occur by neogenesis of beta cells from putative progenitor cells rather than by proliferation of existing beta cells. Claes Hellerström has pioneered the research on beta cell growth for decades...... in the expansion of the beta cell mass in human pregnancy, and the relative roles of endocrine factors and nutrients....

  2. Error Argumentation Enhance Adaptability in Adults With Low Motor Ability.

    Science.gov (United States)

    Lee, Chi-Mei; Bo, Jin

    2016-01-01

    The authors focused on young adults with varying degrees of motor difficulties and examined their adaptability in a visuomotor adaptation task where the visual feedback of participants' movement error was presented with either 1:1 ratio (i.e., regular feedback schedule) or 1:2 ratio (i.e., enhanced feedback schedule). Within-subject design was used with two feedback schedules counter-balanced and separated for 10 days. Results revealed that participants with greater motor difficulties showed less adaptability than those with normal motor abilities in the regular feedback schedule; however, all participants demonstrated similar level of adaptability in the enhanced feedback schedule. The results suggest that error argumentation enhances adaptability in adults with low motor ability.

  3. Enhancing agent safety through autonomous environment adaptation

    CSIR Research Space (South Africa)

    Rosman, Benjamin S

    2015-08-01

    Full Text Available limit their ability to interact with and explore their environments. In this work we address this risk through the incorporation of a caregiver robot, and present a model allowing it to autonomously adapt its environment to minimize danger for other...

  4. Mobilizing local safety nets for enhanced adaptive capacity to ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2016-04-22

    Apr 22, 2016 ... This brief resulted from two projects supported by the Climate Change Adaptation in Africa program: the research project Resilience and the African Smallholder : Enhancing the Capacity of Communities to Adapt to Climate Change and the mentoring project Promoting Participatory Action Research through ...

  5. Dynamical Adaptation in Terrorist Cells/Networks

    DEFF Research Database (Denmark)

    Hussain, Dil Muhammad Akbar; Ahmed, Zaki

    2010-01-01

    Typical terrorist cells/networks have dynamical structure as they evolve or adapt to changes which may occur due to capturing or killing of a member of the cell/network. Analytical measures in graph theory like degree centrality, betweenness and closeness centralities are very common and have long...

  6. Nanoparticles for cells proliferation enhancement

    International Nuclear Information System (INIS)

    Popa, V.; Braniste, F.; Tiginyanu, I.M.; Lisii, C.; Nacu, V.

    2013-01-01

    The potential of semiconductor nanoparticles as stimulator for avian mesenchyme stem cells proliferation enhancement is demonstrated. The effect is related to nanoparticles polarization due to external ultrasound field resulting in local electrical stimulation. Our preliminary results demonstrates that the number of cells have been increased by 23 % ±2%) in cell cultures under the action of external ultrasound stimulation. Morphological analysis and viability shows no differences between the control group and the group studied. These results suggest the possibility for tissue regeneration enhancement by remote stimulation of implanted semiconductor nanoparticles. (authors)

  7. Nonequilibrium Enhances Adaptation Efficiency of Stochastic Biochemical Systems.

    Directory of Open Access Journals (Sweden)

    Chen Jia

    Full Text Available Adaptation is a crucial biological function possessed by many sensory systems. Early work has shown that some influential equilibrium models can achieve accurate adaptation. However, recent studies indicate that there are close relationships between adaptation and nonequilibrium. In this paper, we provide an explanation of these two seemingly contradictory results based on Markov models with relatively simple networks. We show that as the nonequilibrium driving becomes stronger, the system under consideration will undergo a phase transition along a fixed direction: from non-adaptation to simple adaptation then to oscillatory adaptation, while the transition in the opposite direction is forbidden. This indicates that although adaptation may be observed in equilibrium systems, it tends to occur in systems far away from equilibrium. In addition, we find that nonequilibrium will improve the performance of adaptation by enhancing the adaptation efficiency. All these results provide a deeper insight into the connection between adaptation and nonequilibrium. Finally, we use a more complicated network model of bacterial chemotaxis to validate the main results of this paper.

  8. Reward and punishment enhance motor adaptation in stroke.

    Science.gov (United States)

    Quattrocchi, Graziella; Greenwood, Richard; Rothwell, John C; Galea, Joseph M; Bestmann, Sven

    2017-09-01

    The effects of motor learning, such as motor adaptation, in stroke rehabilitation are often transient, thus mandating approaches that enhance the amount of learning and retention. Previously, we showed in young individuals that reward and punishment feedback have dissociable effects on motor adaptation, with punishment improving adaptation and reward enhancing retention. If these findings were able to generalise to patients with stroke, they would provide a way to optimise motor learning in these patients. Therefore, we tested this in 45 patients with chronic stroke allocated in three groups. Patients performed reaching movements with their paretic arm with a robotic manipulandum. After training (day 1), day 2 involved adaptation to a novel force field. During the adaptation phase, patients received performance-based feedback according to the group they were allocated: reward, punishment or no feedback (neutral). On day 3, patients readapted to the force field but all groups now received neutral feedback. All patients adapted, with reward and punishment groups displaying greater adaptation and readaptation than the neutral group, irrespective of demographic, cognitive or functional differences. Remarkably, the reward and punishment groups adapted to similar degree as healthy controls. Finally, the reward group showed greater retention. This study provides, for the first time, evidence that reward and punishment can enhance motor adaptation in patients with stroke. Further research on reinforcement-based motor learning regimes is warranted to translate these promising results into clinical practice and improve motor rehabilitation outcomes in patients with stroke. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Speech Enhancement by Modified Convex Combination of Fractional Adaptive Filtering

    Directory of Open Access Journals (Sweden)

    M. Geravanchizadeh

    2014-12-01

    Full Text Available This paper presents new adaptive filtering techniques used in speech enhancement system. Adaptive filtering schemes are subjected to different trade-offs regarding their steady-state misadjustment, speed of convergence, and tracking performance. Fractional Least-Mean-Square (FLMS is a new adaptive algorithm which has better performance than the conventional LMS algorithm. Normalization of LMS leads to better performance of adaptive filter. Furthermore, convex combination of two adaptive filters improves its performance. In this paper, new convex combinational adaptive filtering methods in the framework of speech enhancement system are proposed. The proposed methods utilize the idea of normalization and fractional derivative, both in the design of different convex mixing strategies and their related component filters. To assess our proposed methods, simulation results of different LMS-based algorithms based on their convergence behavior (i.e., MSE plots and different objective and subjective criteria are compared. The objective and subjective evaluations include examining the results of SNR improvement, PESQ test, and listening tests for dual-channel speech enhancement. The powerful aspects of proposed methods are their low complexity, as expected with all LMS-based methods, along with a high convergence rate.

  10. Enhancement of large fluctuations to extinction in adaptive networks

    Science.gov (United States)

    Hindes, Jason; Schwartz, Ira B.; Shaw, Leah B.

    2018-01-01

    During an epidemic, individual nodes in a network may adapt their connections to reduce the chance of infection. A common form of adaption is avoidance rewiring, where a noninfected node breaks a connection to an infected neighbor and forms a new connection to another noninfected node. Here we explore the effects of such adaptivity on stochastic fluctuations in the susceptible-infected-susceptible model, focusing on the largest fluctuations that result in extinction of infection. Using techniques from large-deviation theory, combined with a measurement of heterogeneity in the susceptible degree distribution at the endemic state, we are able to predict and analyze large fluctuations and extinction in adaptive networks. We find that in the limit of small rewiring there is a sharp exponential reduction in mean extinction times compared to the case of zero adaption. Furthermore, we find an exponential enhancement in the probability of large fluctuations with increased rewiring rate, even when holding the average number of infected nodes constant.

  11. Climate change adaptation among Tibetan pastoralists: challenges in enhancing local adaptation through policy support.

    Science.gov (United States)

    Fu, Yao; Grumbine, R Edward; Wilkes, Andreas; Wang, Yun; Xu, Jian-Chu; Yang, Yong-Ping

    2012-10-01

    While researchers are aware that a mix of Local Ecological Knowledge (LEK), community-based resource management institutions, and higher-level institutions and policies can facilitate pastoralists' adaptation to climate change, policy makers have been slow to understand these linkages. Two critical issues are to what extent these factors play a role, and how to enhance local adaptation through government support. We investigated these issues through a case study of two pastoral communities on the Tibetan Plateau in China employing an analytical framework to understand local climate adaptation processes. We concluded that LEK and community-based institutions improve adaptation outcomes for Tibetan pastoralists through shaping and mobilizing resource availability to reduce risks. Higher-level institutions and policies contribute by providing resources from outside communities. There are dynamic interrelationships among these factors that can lead to support, conflict, and fragmentation. Government policy could enhance local adaptation through improvement of supportive relationships among these factors. While central government policies allow only limited room for overt integration of local knowledge/institutions, local governments often have some flexibility to buffer conflicts. In addition, government policies to support market-based economic development have greatly benefited adaptation outcomes for pastoralists. Overall, in China, there are still questions over how to create innovative institutions that blend LEK and community-based institutions with government policy making.

  12. Plant Cell Adaptive Responses to Microgravity

    Science.gov (United States)

    Kordyum, Elizabeth; Kozeko, Liudmyla; Talalaev, Alexandr

    Microgravity is an abnormal environmental condition that plays no role in the functioning of biosphere. Nevertheless, the chronic effect of microgravity in space flight as an unfamiliar factor does not prevent the development of adaptive reactions at the cellular level. In real microgravity in space flight under the more or less optimal conditions for plant growing, namely temperature, humidity, CO2, light intensity and directivity in the hardware angiosperm plants perform an “reproductive imperative”, i.e. they flower, fruit and yield viable seeds. It is known that cells of a multicellular organism not only take part on reactions of the organism but also carry out processes that maintain their integrity. In light of these principles, the problem of the identification of biochemical, physiological and structural patterns that can have adaptive significance at the cellular and subcellular level in real and simulated microgravity is considered. Cytological studies of plants developing in real and simulated microgravity made it possible to establish that the processes of mitosis, cytokinesis, and tissue differentiation of vegetative and generative organs are largely normal. At the same time, under microgravity, essential reconstruction in the structural and functional organization of cell organelles and cytoskeleton, as well as changes in cell metabolism and homeostasis have been described. In addition, new interesting data concerning the influence of altered gravity on lipid peroxidation intensity, the level of reactive oxygen species, and antioxidant system activity, just like on the level of gene expression and synthesis of low-molecular and high-molecular heat shock proteins were recently obtained. So, altered gravity caused time-dependent increasing of the HSP70 and HSP90 levels in cells, that may indicate temporary strengthening of their functional loads that is necessary for re-establish a new cellular homeostasis. Relative qPCR results showed that

  13. Adaptive radiotherapy based on contrast enhanced cone beam CT imaging

    International Nuclear Information System (INIS)

    Soevik, Aaste; Skogmo, Hege K.; Roedal, Jan; Lervaag, Christoffer; Eilertsen, Karsten; Malinen, Eirik

    2010-01-01

    Cone beam CT (CBCT) imaging has become an integral part of radiation therapy, with images typically used for offline or online patient setup corrections based on bony anatomy co-registration. Ideally, the co-registration should be based on tumor localization. However, soft tissue contrast in CBCT images may be limited. In the present work, contrast enhanced CBCT (CECBCT) images were used for tumor visualization and treatment adaptation. Material and methods. A spontaneous canine maxillary tumor was subjected to repeated cone beam CT imaging during fractionated radiotherapy (10 fractions in total). At five of the treatment fractions, CECBCT images, employing an iodinated contrast agent, were acquired, as well as pre-contrast CBCT images. The tumor was clearly visible in post-contrast minus pre-contrast subtraction images, and these contrast images were used to delineate gross tumor volumes. IMRT dose plans were subsequently generated. Four different strategies were explored: 1) fully adapted planning based on each CECBCT image series, 2) planning based on images acquired at the first treatment fraction and patient repositioning following bony anatomy co-registration, 3) as for 2), but with patient repositioning based on co-registering contrast images, and 4) a strategy with no patient repositioning or treatment adaptation. The equivalent uniform dose (EUD) and tumor control probability (TCP) calculations to estimate treatment outcome for each strategy. Results. Similar translation vectors were found when bony anatomy and contrast enhancement co-registration were compared. Strategy 1 gave EUDs closest to the prescription dose and the highest TCP. Strategies 2 and 3 gave EUDs and TCPs close to that of strategy 1, with strategy 3 being slightly better than strategy 2. Even greater benefits from strategies 1 and 3 are expected with increasing tumor movement or deformation during treatment. The non-adaptive strategy 4 was clearly inferior to all three adaptive strategies

  14. Financial incentives enhance adaptation to a sensorimotor transformation.

    Science.gov (United States)

    Gajda, Kathrin; Sülzenbrück, Sandra; Heuer, Herbert

    2016-10-01

    Adaptation to sensorimotor transformations has received much attention in recent years. However, the role of motivation and its relation to the implicit and explicit processes underlying adaptation has been neglected thus far. Here, we examine the influence of extrinsic motivation on adaptation to a visuomotor rotation by way of providing financial incentives for accurate movements. Participants in the experimental group "bonus" received a defined amount of money for high end-point accuracy in a visuomotor rotation task; participants in the control group "no bonus" did not receive a financial incentive. Results showed better overall adaptation to the visuomotor transformation in participants who were extrinsically motivated. However, there was no beneficial effect of financial incentives on the implicit component, as assessed by the after-effects, and on separately assessed explicit knowledge. These findings suggest that the positive influence of financial incentives on adaptation is due to a component which cannot be measured by after-effects or by our test of explicit knowledge. A likely candidate is model-free learning based on reward-prediction errors, which could be enhanced by the financial bonuses.

  15. Capillary Electrophoresis Sensitivity Enhancement Based on Adaptive Moving Average Method.

    Science.gov (United States)

    Drevinskas, Tomas; Telksnys, Laimutis; Maruška, Audrius; Gorbatsova, Jelena; Kaljurand, Mihkel

    2018-06-05

    In the present work, we demonstrate a novel approach to improve the sensitivity of the "out of lab" portable capillary electrophoretic measurements. Nowadays, many signal enhancement methods are (i) underused (nonoptimal), (ii) overused (distorts the data), or (iii) inapplicable in field-portable instrumentation because of a lack of computational power. The described innovative migration velocity-adaptive moving average method uses an optimal averaging window size and can be easily implemented with a microcontroller. The contactless conductivity detection was used as a model for the development of a signal processing method and the demonstration of its impact on the sensitivity. The frequency characteristics of the recorded electropherograms and peaks were clarified. Higher electrophoretic mobility analytes exhibit higher-frequency peaks, whereas lower electrophoretic mobility analytes exhibit lower-frequency peaks. On the basis of the obtained data, a migration velocity-adaptive moving average algorithm was created, adapted, and programmed into capillary electrophoresis data-processing software. Employing the developed algorithm, each data point is processed depending on a certain migration time of the analyte. Because of the implemented migration velocity-adaptive moving average method, the signal-to-noise ratio improved up to 11 times for sampling frequency of 4.6 Hz and up to 22 times for sampling frequency of 25 Hz. This paper could potentially be used as a methodological guideline for the development of new smoothing algorithms that require adaptive conditions in capillary electrophoresis and other separation methods.

  16. Past seawater experience enhances seawater adaptability in medaka, Oryzias latipes.

    Science.gov (United States)

    Miyanishi, Hiroshi; Inokuchi, Mayu; Nobata, Shigenori; Kaneko, Toyoji

    2016-01-01

    During the course of evolution, fishes have acquired adaptability to various salinity environments, and acquirement of seawater (SW) adaptability has played important roles in fish evolution and diversity. However, little is known about how saline environments influence the acquirement of SW adaptability. The Japanese medaka Oryzias latipes is a euryhaline species that usually inhabits freshwater (FW), but is also adaptable to full-strength SW when transferred through diluted SW. In the present study, we examined how past SW experience affects hyposmoregulatory ability in Japanese medaka. For the preparation of SW-experienced fish, FW medaka were acclimated to SW after pre-acclimation to 1/2 SW, and the SW-acclimated fish were transferred back to FW. The SW-experienced fish and control FW fish (SW-inexperienced fish) were transferred directly to SW. Whereas control FW fish did not survive direct transfer to SW, 1/4 of SW-experienced fish adapted successfully to SW. Although there were no significant differences in blood osmolality and plasma Na(+) and Cl(-) concentrations between SW-experienced and control FW medaka in FW, increments in these parameters following SW transfer were lower in SW-experienced fish than in control FW fish. The gene expression of SW-type Na(+), K(+)-ATPase (NKA) in the gills of SW-experienced medaka increased more quickly after direct SW transfer compared with the expression in control FW fish. Prior to SW transfer, the density of NKA-immunoreactive ionocytes in the gills was higher in SW-experienced fish than in control FW fish. Ionocytes expressing CFTR Cl(-) channel at the apical membrane and those forming multicellular complexes, both of which were characteristic of SW-type ionocytes, were also increased in SW-experienced fish. These results indicate that past SW experience enhances the capacity of Na(+) and Cl(-) secretion in ionocytes and thus hypoosmoregulatory ability of Japanese medaka, suggesting the presence of epigenetic

  17. Nrf2 mediates redox adaptation in NOX4-overexpressed non-small cell lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Qipeng; Yao, Bei; Li, Ning; Ma, Lei; Deng, Yanchao; Yang, Yang; Zeng, Cheng; Yang, Zhicheng [Department of Clinical Pharmacy, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006 (China); Liu, Bing, E-mail: liubing520@gdpu.edu.cn [Department of Clinical Pharmacy, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006 (China); Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006 (China)

    2017-03-15

    The redox adaptation mechanisms in cancer cells are very complex and remain largely unclear. Our previous studies have confirmed that NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and confers apoptosis resistance on NSCLC cells. However, the comprehensive mechanisms for NOX4-mediated oxidative resistance of cancer cells remain still undentified. The present study found that NOX4-derived H{sub 2}O{sub 2} enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) stability via disruption of redox-dependent proteasomal degradation and stimulated its activity through activation of PI3K signaling. Specifically, the results showed that ectopic NOX4 expression did not induce apoptosis of A549 cells; however, inhibition of Nrf2 resulted in obvious apoptotic death of NOX4-overexpressed A549 cells, accompanied by a significant increase in H{sub 2}O{sub 2} level and decrease in GSH content. Besides, inhibition of Nrf2 could suppress cell growth and efficiently reverse the enhancement effect of NOX4 on cell growth. The in vivo data confirmed that inhibition of Nrf2 could interfere apoptosis resistance in NOX4-overexpressed A549 tumors and led to cell growth inhibition. In conclusion, these results reveal that Nrf2 is critically involved in redox adaptation regulation in NOX4-overexpressed NSCLC cells. Therefore, NOX4 and Nrf2 may be promising combination targets against malignant progression of NSCLC. - Highlights: • NOX4-derived H{sub 2}O{sub 2} upregulates Nrf2 expression and activity in NSCLC. • Nrf2 confers apoptosis resistance in NOX4-overexpressed NSCLC cells. • Inhibition of Nrf2 reverses the enhancement effect of NOX4 on cell growth.

  18. 75 FR 34988 - Federal Advisory Committee; Defense Science Board 2010 Summer Study on Enhancing Adaptability of...

    Science.gov (United States)

    2010-06-21

    ... 2010 Summer Study on Enhancing Adaptability of Our Military Forces AGENCY: Department of Defense (DoD... Enhancing Adaptability of our Military Forces will meet in closed session from August 2-13, 2010, in... establish defining metrics and identifying fundamental attributes of an architecture to enhance adaptability...

  19. An Enhanced Jaya Algorithm with a Two Group Adaption

    Directory of Open Access Journals (Sweden)

    Chibing Gong

    2017-01-01

    Full Text Available This paper proposes a novel performance enhanced Jaya algorithm with a two group adaption (E-Jaya. Two improvements are presented in E-Jaya. First, instead of using the best and the worst values in Jaya algorithm, EJaya separates all candidates into two groups: the better and the worse groups based on their fitness values, then the mean of the better group and the mean of the worse group are used. Second, in order to add non algorithm-specific parameters in E-Jaya, a novel adaptive method of dividing the two groups has been developed. Finally, twelve benchmark functions with different dimensionality, such as 40, 60, and 100, were evaluated using the proposed EJaya algorithm. The results show that E-Jaya significantly outperformed Jaya algorithm in terms of the solution accuracy. Additionally, E-Jaya was also compared with a differential evolution (DE, a self-adapting control parameters in differential evolution (jDE, a firefly algorithm (FA, and a standard particle swarm optimization 2011 (SPSO2011 algorithm. E-Jaya algorithm outperforms all the algorithms.

  20. Adaptive enhanced sampling by force-biasing using neural networks

    Science.gov (United States)

    Guo, Ashley Z.; Sevgen, Emre; Sidky, Hythem; Whitmer, Jonathan K.; Hubbell, Jeffrey A.; de Pablo, Juan J.

    2018-04-01

    A machine learning assisted method is presented for molecular simulation of systems with rugged free energy landscapes. The method is general and can be combined with other advanced sampling techniques. In the particular implementation proposed here, it is illustrated in the context of an adaptive biasing force approach where, rather than relying on discrete force estimates, one can resort to a self-regularizing artificial neural network to generate continuous, estimated generalized forces. By doing so, the proposed approach addresses several shortcomings common to adaptive biasing force and other algorithms. Specifically, the neural network enables (1) smooth estimates of generalized forces in sparsely sampled regions, (2) force estimates in previously unexplored regions, and (3) continuous force estimates with which to bias the simulation, as opposed to biases generated at specific points of a discrete grid. The usefulness of the method is illustrated with three different examples, chosen to highlight the wide range of applicability of the underlying concepts. In all three cases, the new method is found to enhance considerably the underlying traditional adaptive biasing force approach. The method is also found to provide improvements over previous implementations of neural network assisted algorithms.

  1. Cloned Hemoglobin Genes Enhance Growth Of Cells

    Science.gov (United States)

    Khosla, Chaitan; Bailey, James E.

    1991-01-01

    Experiments show that portable deoxyribonucleic acid (DNA) sequences incorporated into host cells make them produce hemoglobins - oxygen-binding proteins essential to function of red blood cells. Method useful in several biotechnological applications. One, enhancement of growth of cells at higher densities. Another, production of hemoglobin to enhance supplies of oxygen in cells, for use in chemical reactions requiring oxygen, as additive to serum to increase transport of oxygen, and for binding and separating oxygen from mixtures of gases.

  2. Phenomenon of adaptive response of cells in radiobiology

    International Nuclear Information System (INIS)

    Fillipovich, I.V.

    1991-01-01

    Consideration is given to various adaptive reactions to low-level radiation, their association with an absorbed dose, dose rate, radiation quality and time-interval between exposures, as well as with a cell cycle phase. Possible mechanisms of the adaptive response and the character and role of DNA damages, that can induce gene expression of the adaptive response, are discussed. The data on the influence of a preliminary long-term exposure to low-level radiation on the radiosensitivity of biological objects are analyzed with due regard for the adaptive cell response. It is concluded that the adaptive response of cells to ionizing radiation is a particular case of the phenomenon of cell adaptation of the effect of genotoxic factors of the environment

  3. Mechano-adaptation of the stem cell nucleus.

    Science.gov (United States)

    Heo, Su-Jin; Cosgrove, Brian D; Dai, Eric N; Mauck, Robert L

    2018-01-01

    Exogenous mechanical forces are transmitted through the cell and to the nucleus, initiating mechanotransductive signaling cascades with profound effects on cellular function and stem cell fate. A growing body of evidence has shown that the force sensing and force-responsive elements of the nucleus adapt to these mechanotransductive events, tuning their response to future mechanical input. The mechanisms underlying this "mechano-adaptation" are only just beginning to be elucidated, and it remains poorly understood how these components act and adapt in tandem to drive stem cell differentiation. Here, we review the evidence on how the stem cell nucleus responds and adapts to physical forces, and provide a perspective on how this mechano-adaptation may function to drive and enforce stem cell differentiation.

  4. Adaptation.

    Science.gov (United States)

    Broom, Donald M

    2006-01-01

    The term adaptation is used in biology in three different ways. It may refer to changes which occur at the cell and organ level, or at the individual level, or at the level of gene action and evolutionary processes. Adaptation by cells, especially nerve cells helps in: communication within the body, the distinguishing of stimuli, the avoidance of overload and the conservation of energy. The time course and complexity of these mechanisms varies. Adaptive characters of organisms, including adaptive behaviours, increase fitness so this adaptation is evolutionary. The major part of this paper concerns adaptation by individuals and its relationships to welfare. In complex animals, feed forward control is widely used. Individuals predict problems and adapt by acting before the environmental effect is substantial. Much of adaptation involves brain control and animals have a set of needs, located in the brain and acting largely via motivational mechanisms, to regulate life. Needs may be for resources but are also for actions and stimuli which are part of the mechanism which has evolved to obtain the resources. Hence pigs do not just need food but need to be able to carry out actions like rooting in earth or manipulating materials which are part of foraging behaviour. The welfare of an individual is its state as regards its attempts to cope with its environment. This state includes various adaptive mechanisms including feelings and those which cope with disease. The part of welfare which is concerned with coping with pathology is health. Disease, which implies some significant effect of pathology, always results in poor welfare. Welfare varies over a range from very good, when adaptation is effective and there are feelings of pleasure or contentment, to very poor. A key point concerning the concept of individual adaptation in relation to welfare is that welfare may be good or poor while adaptation is occurring. Some adaptation is very easy and energetically cheap and

  5. Adaptive and freeze-tolerant heteronetwork organohydrogels with enhanced mechanical stability over a wide temperature range

    Science.gov (United States)

    Gao, Hainan; Zhao, Ziguang; Cai, Yudong; Zhou, Jiajia; Hua, Wenda; Chen, Lie; Wang, Li; Zhang, Jianqi; Han, Dong; Liu, Mingjie; Jiang, Lei

    2017-06-01

    Many biological organisms with exceptional freezing tolerance can resist the damages to cells from extra-/intracellular ice crystals and thus maintain their mechanical stability at subzero temperatures. Inspired by the freezing tolerance mechanisms found in nature, here we report a strategy of combining hydrophilic/oleophilic heteronetworks to produce self-adaptive, freeze-tolerant and mechanically stable organohydrogels. The organohydrogels can simultaneously use water and oil as a dispersion medium, and quickly switch between hydrogel- and organogel-like behaviours in response to the nature of the surrounding phase. Accordingly, their surfaces display unusual adaptive dual superlyophobic in oil/water system (that is, they are superhydrophobic under oil and superoleophobic under water). Moreover, the organogel component can inhibit the ice crystallization of the hydrogel component, thus enhancing the mechanical stability of organohydrogel over a wide temperature range (-78 to 80 °C). The organohydrogels may have promising applications in complex and harsh environments.

  6. Opportunities for adaptive online collaboration to enhance rural land management.

    Science.gov (United States)

    Baumber, Alex; Metternicht, Graciela; Ampt, Peter; Cross, Rebecca; Berry, Emily

    2018-08-01

    Cross-property cooperation has the potential to enhance the effectiveness of environmental management actions that cut across property boundaries. Online tools can facilitate this and overcome barriers to landholder engagement in collaborative management. However, collaborative online tools need to be designed and tailored to users' needs and values, and landholder participation in the development process is critical to ensuring uptake and long-term use. This article presents a case study from the Central Tablelands region of New South Wales, Australia, where landholders have been involved in participatory development of a new online collaboration tool. The case study results highlight the significance of issues such as internet access, privacy, technical proficiency and differing stakeholder objectives. A landholder survey identified mapping and the uploading of monitoring data as important functions for the online tool, but these were not rated as highly as functions relating to data security, sharing settings and key term searches. Consequently, we recommend that a future online collaboration tool for the region is not framed specifically as a mapping or citizen science tool, but rather as an adaptive collaboration and communication tool that can incorporate a variety of data types and formats and be modified over time in line with changing landholder needs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Proteins associated with adaptation of cultured tobacco cells to NaCl

    International Nuclear Information System (INIS)

    Singh, N.K.; Handa, A.K.; Hasegawa, P.M.; Bressan, R.A.

    1985-01-01

    Cultured tobacco cells (Nicotiana tabacum L. cv Wisconsin 38) adapted to grow in medium containing high levels of NaCl or polyethylene glycol (PEG) produce several new or enhanced polypeptide bands on sodium dodecyl sulfate-polyarylamide gel electrophoresis. The intensities of some of the polypeptide bands increase with increasing levels of NaCl adaptation, while the intensities of other polypeptide bands are reduced. Synthesis of 26-kilodalton polypeptide(s) occurs at two different periods during culture growth of NaCl adapted cells. Unadapted cells also incorporate 35 S into a 26-kilodalton polypeptide during the later stage of culture growth beginning at midlog phase. The 26-kilodalton polypeptides from adapted and unadapted cells have similar partial proteolysis peptide maps and are immunologically cross-reactive. During adaptation to NaCl, unadapted cells synthesize and accumulate a major 26-kilodalton polypeptide, and the beginning of synthesis corresponds to the period of osmotic adjustment and culture growth. From their results, the authors suggest an involvement of the 26-kilodalton polypeptide in the adaptation of cultured tobacco cells to NaCl and water stress. 38 references, 11 figures, 2 tables

  8. CD8 T Cell Sensory Adaptation Dependent on TCR Avidity for Self-Antigens

    DEFF Research Database (Denmark)

    Marquez, M.-E.; Ellmeier, W.; Sanchez-Guajardo, Vanesa Maria

    2005-01-01

    dephosphorylation of linker for activation of T cells and ERK upon activation. Normal TCR levels and cytokine production were restored by culturing cells in the absence of TCR/spMHC interaction, demonstrating dynamic tuning of peripheral T cell responses. The effect of avidity for self-ligand(s) on this sensory...... ZAP-YEEI cells were enhanced. Our data provide support for central and peripheral sensory T cell adaptation induced as a function of TCR avidity for self-ligands and signaling level. This may contribute to buffer excessive autoreactivity while optimizing TCR repertoire usage....

  9. Studies on adaptive responses in Chinese hamster cells

    International Nuclear Information System (INIS)

    Michelin, S.C.; Perez, M.R. Del; Dubner, D.; Gisone, P.A.

    1997-01-01

    For many years the possibility has been considered of low doses of radiation inducing adaptive responses in cells and organisms against the mutagenic effects of radiation. Currently, a number of experimental data appraise the existence of an adaptive response that is characterized by a decrease of radiation induced genetic damages. The understanding of the molecular mechanism involved in this phenomenon permits to estimate the effects and risks of low dose exposure. In this work, preliminary results of studies on the induction of adaptive response in cells subjected to different doses of ionizing radiation are presented

  10. Enhanced vaccine control of epidemics in adaptive networks

    Science.gov (United States)

    Shaw, Leah B.; Schwartz, Ira B.

    2010-04-01

    We study vaccine control for disease spread on an adaptive network modeling disease avoidance behavior. Control is implemented by adding Poisson-distributed vaccination of susceptibles. We show that vaccine control is much more effective in adaptive networks than in static networks due to feedback interaction between the adaptive network rewiring and the vaccine application. When compared to extinction rates in static social networks, we find that the amount of vaccine resources required to sustain similar rates of extinction are as much as two orders of magnitude lower in adaptive networks.

  11. Pluripotent cells display enhanced resistance to mutagenesis

    Directory of Open Access Journals (Sweden)

    Daniel J. Cooper

    2017-03-01

    Full Text Available Pluripotent cells have been reported to exhibit lower frequencies of point mutations and higher levels of DNA repair than differentiated cells. This predicts that pluripotent cells are less susceptible to mutagenic exposures than differentiated cells. To test this prediction, we used a lacI mutation-reporter transgene system to assess the frequency of point mutations in multiple lines of mouse pluripotent embryonic stem cells and induced pluripotent cells, as well as in multiple lines of differentiated fibroblast cells, before and after exposure to a moderate dose of the mutagen, methyl methanesulfonate. We also measured levels of key enzymes in the base excision repair (BER pathway in each cell line before and after exposure to the mutagen. Our results confirm that pluripotent cells normally maintain lower frequencies of point mutations than differentiated cells, and show that differentiated cells exhibit a large increase in mutation frequency following a moderate mutagenic exposure, whereas pluripotent cells subjected to the same exposure show no increase in mutations. This result likely reflects the higher levels of BER proteins detectable in pluripotent cells prior to exposure and supports our thesis that maintenance of enhanced genetic integrity is a fundamental characteristic of pluripotent cells.

  12. Enhancing Functional Performance using Sensorimotor Adaptability Training Programs

    Science.gov (United States)

    Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Brady, R.; Audas, C.; Ruttley, T. M.; Cohen, H. S.

    2009-01-01

    During the acute phase of adaptation to novel gravitational environments, sensorimotor disturbances have the potential to disrupt the ability of astronauts to perform functional tasks. The goal of this project is to develop a sensorimotor adaptability (SA) training program designed to facilitate recovery of functional capabilities when astronauts transition to different gravitational environments. The project conducted a series of studies that investigated the efficacy of treadmill training combined with a variety of sensory challenges designed to increase adaptability including alterations in visual flow, body loading, and support surface stability.

  13. Adaptation of cell renewal systems under continuous irradiation

    International Nuclear Information System (INIS)

    Fabrikant, J.I.

    1987-01-01

    There are adaptive changes in the proliferative characteristics of renewal tissues under the stress of continuous low-dose-rate irradiation which indicate that cell and tissue kinetics will have a considerable effect on the radiation response. Factors that determine the adaptation response involve cellular radiosensitivity, i.e. cell cycle effects, which determine the rate of cell sterilization and death, and compensatory cell proliferation and the capacity for regeneration, i.e. changes in the patterns of cell population kinetics, which determine the rate of cell birth. In rapidly dividing cell renewal systems, there is an effective elimination of damaged cells, with almost complete repair of cellular nonlethal damage. In slowly dividing renewal tissues, there is some repair or elimination of cellular radiation damage and the pattern of cell proliferation during regeneration is relatively little disturbed by prior continuous irradiation. Experimental data on intestinal epithelium, immunohematopoietic tissues, seminiferous epithelium and regenerating liver are presented. Discussion includes differences in adaptation to continuous low-dose-rate irradiation involving intracellular and extracellular control mechanisms which regulate cellular proliferation and differentiation and, thereby, control cell population levels and physiological function. 29 references

  14. M-Eco enhanced Adaptation Service (D5.2)

    DEFF Research Database (Denmark)

    Dolog, Peter; Durao, Frederico; Lage, Ricardo Gomes

    2012-01-01

    In this report, we present the improvements of the Adaptive Tuning and Personalization (WP5) component of the M-Eco system. This component is focused on four main areas of interest to users of surveillance systems: presentation options for recommendation and adaptation, user and group models, use...... interests. The main contributions of the report are spatial reasoning methods evaluated in group recommendations, personalized tag clouds, and web services integration....

  15. The activation of the adaptive immune system: cross-talk between antigen-presenting cells, T cells and B cells.

    Science.gov (United States)

    den Haan, Joke M M; Arens, Ramon; van Zelm, Menno C

    2014-12-01

    The adaptive immune system consists of T and B cells that express clonally distributed antigen receptors. To achieve functional adaptive immune responses, antigen-specific T cell populations are stimulated by professional antigen-presenting cells like dendritic cells (DCs), which provide crucial stimulatory signals for efficient expansion and development of effector functions. Antigen-specific B cells receive costimulatory signals from helper T cells to stimulate affinity maturation and isotype switching. Here we elaborate on the interactions between DCs, T cells and B cells, and on the important signals for efficient induction of adaptive immune responses. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Temporal adaptation enhances efficient contrast gain control on natural images.

    Directory of Open Access Journals (Sweden)

    Fabian Sinz

    Full Text Available Divisive normalization in primary visual cortex has been linked to adaptation to natural image statistics in accordance to Barlow's redundancy reduction hypothesis. Using recent advances in natural image modeling, we show that the previously studied static model of divisive normalization is rather inefficient in reducing local contrast correlations, but that a simple temporal contrast adaptation mechanism of the half-saturation constant can substantially increase its efficiency. Our findings reveal the experimentally observed temporal dynamics of divisive normalization to be critical for redundancy reduction.

  17. Mast cells enhance T cell activation: Importance of mast cell-derived TNF

    Science.gov (United States)

    Nakae, Susumu; Suto, Hajime; Kakurai, Maki; Sedgwick, Jonathon D.; Tsai, Mindy; Galli, Stephen J.

    2005-05-01

    Mast cells are not only important effector cells in immediate hypersensitivity reactions and immune responses to pathogens but also can contribute to T cell-mediated disorders. However, the mechanisms by which mast cells might influence T cells in such settings are not fully understood. We find that mast cells can enhance proliferation and cytokine production in multiple T cell subsets. Mast cell-dependent enhancement of T cell activation can be promoted by FcRI-dependent mast cell activation, TNF production by both mast cells and T cells, and mast cell-T cell contact. However, at high concentrations of cells, mast cells can promote T cell activation independent of IgE or TNF. Finally, mast cells also can promote T cell activation by means of soluble factors. These findings identify multiple mechanisms by which mast cells can influence T cell proliferation and cytokine production. allergy | asthma | autoimmunity | cytokines | immune response

  18. Parametric Adaptive Radar Detector with Enhanced Mismatched Signals Rejection Capabilities

    Directory of Open Access Journals (Sweden)

    Liu Bin

    2010-01-01

    Full Text Available We consider the problem of adaptive signal detection in the presence of Gaussian noise with unknown covariance matrix. We propose a parametric radar detector by introducing a design parameter to trade off the target sensitivity with sidelobes energy rejection. The resulting detector merges the statistics of Kelly's GLRT and of the Rao test and so covers Kelly's GLRT and the Rao test as special cases. Both invariance properties and constant false alarm rate (CFAR behavior for this detector are studied. At the analysis stage, the performance of the new receiver is assessed and compared with several traditional adaptive detectors. The results highlight better rejection capabilities of this proposed detector for mismatched signals. Further, we develop two two-stage detectors, one of which consists of an adaptive matched filter (AMF followed by the aforementioned detector, and the other is obtained by cascading a GLRT-based Subspace Detector (SD and the proposed adaptive detector. We show that the former two-stage detector outperforms traditional two-stage detectors in terms of selectivity, and the latter yields more robustness.

  19. Design Framework for an Adaptive MOOC Enhanced by Blended Learning

    DEFF Research Database (Denmark)

    Gynther, Karsten

    2016-01-01

    The research project has developed a design framework for an adaptive MOOC that complements the MOOC format with blended learning. The design framework consists of a design model and a series of learning design principles which can be used to design in-service courses for teacher professional...

  20. Enhancing Climate Change Adaptation in Agriculture and Water ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Climate change extremes such as flooding and seasonal drought are already undermining the economies of countries in the Horn of Africa, with agriculture and water resources being the most affected sectors. Countries are drawing up national adaptation programs of action (NAPAs) to serve as roadmaps for future ...

  1. ADAPTER: Analysing and developing adaptability and performance in teams to enhance resilience

    International Nuclear Information System (INIS)

    Beek, Dolf van der; Schraagen, Jan Maarten

    2015-01-01

    In the current study, the concept of team resilience was operationalized by developing a first version of a questionnaire (ADAPTER) driven by the four essential abilities of resilience (Hollnagel E, 2011, Resilience engineering in practice: a guidebook, p. 275–96) and expanded with more relation-oriented abilities of leadership and cooperation. The development and administration of ADAPTER took place within two companies. Factor analyses using data of 91 participants largely supported the hypothesized 6-dimension taxonomy. Support was found for Team responding behavior, Shared Leadership and Cooperation with other teams/departments. Anticipation showed considerable overlap with the monitoring scale, possibly due to the fact that monitoring items dealt with prospective situations. Using ADAPTER questionnaire results as a starting point for further in-depth discussion among the different teams in the pilot companies proved very useful. Suggestions for future research include contextualizing the questionnaire by embedding it in actual cases or having it filled in after specific incidents. Also, support of organization should be included as a separate dimension in ADAPTER. - Highlights: • Development of a team resilience questionnaire (ADAPTER). • Driven by Hollnagel's resilience abilities plus shared leadership and cooperation. • Pilot testing of ADAPTER took place within two companies. • Factor analyses (N=91) largely supported the hypothesized 6-dimension taxonomy. • Results provide a useful starting point for further in-depth discussions

  2. Enhancing climate adaptation capacity for drinking water treatment facilities (supplement)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Historical water quality data of the Ohio River. This dataset is associated with the following publication: Levine, A., J. Yang , and J. Goodrich. Enhancing climate...

  3. β-Cell Adaptability during Pregnancy

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis; Horn, Signe; Kirkegaard, Jeanette S.

    2016-01-01

    Pregnancy is a physiological condition associated with β-cell mass expansion occurring in response to increased insulin demand. If the insulin resistance is not compensated by proper augmented insulin production gestational diabetes will occur. As reviewed herein, pregnancy induced hormonal changes...... have occupied scientists since the beginning of the last century where important discoveries of the hormonal regulation of metabolism during pregnancy have been accomplished. Of the multiple hormonal and metabolic changes the somatolactogenic hormones, placental lactogens (PL) and placental growth...... and function during pregnancy have been elucidated. This has identified contributions of a number of known peptide hormones and growth factors (EGF, NGF, HGF, IGFs, GLP-1) and steroid hormones (progesterone, estrogens, glucocorticoids). In addition, glucokinase has been found to be essential for the both...

  4. Enhancing Student Adaption to a Case Based Learning Environment

    DEFF Research Database (Denmark)

    Jensen, Lars Peter

    2010-01-01

    these at the end of the semester, showing the development of the student in terms of adapting to the learning model. The idea will be explained more closely in the final paper. RESEARCH METHOD The research part of the experiment was carried out as action research, as the teacher of the course in the same time......INTRODUCTION Since Aalborg University (AAU) was started it has been using an educational model, where Problem Based Learning is the turning point. Each semester the students on the Engineering Educations form groups of 3-6 persons, which uses half of the study time within the semester to solve......) in groups. It appeared to be difficult for the students to adapt to two different PBL approaches at the same time, and with the project being the most popular the learning outcome of the case studies was not satisfactory after the first semester, but improved on the following semesters. In 2009...

  5. Adaptive Media Streaming to Mobile Devices: Challenges, Enhancements, and Recommendations

    OpenAIRE

    Evensen, Kristian; Kupka, Tomas; Riiser, Haakon; Ni, Pengpeng; Eg, Ragnhild; Griwodz, Carsten; Halvorsen, Pål

    2014-01-01

    Video streaming is predicted to become the dominating traffic in mobile broadband networks. At the same time, adaptive HTTP streaming is developing into the preferred way of streaming media over the Internet. In this paper, we evaluate how different components of a streaming system can be optimized when serving content to mobile devices in particular. We first analyze the media traffic from a Norwegian network and media provider. Based on our findings, we outline benefits and chal...

  6. WWER core pattern enhancement using adaptive improved harmony search

    Energy Technology Data Exchange (ETDEWEB)

    Nazari, T. [Nuclear Engineering Department, Shahid Beheshti University, G.C., P.O. Box 1983963113, Tehran (Iran, Islamic Republic of); Aghaie, M., E-mail: M_Aghaie@sbu.ac.ir [Nuclear Engineering Department, Shahid Beheshti University, G.C., P.O. Box 1983963113, Tehran (Iran, Islamic Republic of); Zolfaghari, A.; Minuchehr, A.; Norouzi, A. [Nuclear Engineering Department, Shahid Beheshti University, G.C., P.O. Box 1983963113, Tehran (Iran, Islamic Republic of)

    2013-01-15

    Highlights: Black-Right-Pointing-Pointer The classical and improved harmony search algorithms are introduced. Black-Right-Pointing-Pointer The advantage of IHS is demonstrated in Shekel's Foxholes. Black-Right-Pointing-Pointer The CHS and IHS are compared with other Heuristic algorithms. Black-Right-Pointing-Pointer The adaptive improved harmony search is applied for two cases. Black-Right-Pointing-Pointer Two cases of WWER core are optimized in BOC FA pattern. - Abstract: The efficient operation and fuel management of PWRs are of utmost importance. Core performance analysis constitutes an essential phase in core fuel management optimization. Finding an optimum core arrangement for loading of fuel assemblies, FAs, in a nuclear core is a complex problem. In this paper, application of classical harmony search (HS) and adaptive improved harmony search (IHS) in loading pattern (LP) design, for pressurized water reactors, is described. In this analysis, finding the best core pattern, which attains maximum multiplication factor, k{sub eff}, by considering maximum allowable power picking factors (PPF) is the main objective. Therefore a HS based, LP optimization code is prepared and CITATION code which is a neutronic calculation code, applied to obtain effective multiplication factor, neutron fluxes and power density in desired cores. Using adaptive improved harmony search and neutronic code, generated LP optimization code, could be applicable for PWRs core with many numbers of FAs. In this work, at first step, HS and IHS efficiencies are compared with some other heuristic algorithms in Shekel's Foxholes problem and capability of the adaptive improved harmony search is demonstrated. Results show, efficient application of IHS. At second step, two WWER cases are studied and then IHS proffered improved core patterns with regard to mentioned objective functions.

  7. WWER core pattern enhancement using adaptive improved harmony search

    International Nuclear Information System (INIS)

    Nazari, T.; Aghaie, M.; Zolfaghari, A.; Minuchehr, A.; Norouzi, A.

    2013-01-01

    Highlights: ► The classical and improved harmony search algorithms are introduced. ► The advantage of IHS is demonstrated in Shekel's Foxholes. ► The CHS and IHS are compared with other Heuristic algorithms. ► The adaptive improved harmony search is applied for two cases. ► Two cases of WWER core are optimized in BOC FA pattern. - Abstract: The efficient operation and fuel management of PWRs are of utmost importance. Core performance analysis constitutes an essential phase in core fuel management optimization. Finding an optimum core arrangement for loading of fuel assemblies, FAs, in a nuclear core is a complex problem. In this paper, application of classical harmony search (HS) and adaptive improved harmony search (IHS) in loading pattern (LP) design, for pressurized water reactors, is described. In this analysis, finding the best core pattern, which attains maximum multiplication factor, k eff , by considering maximum allowable power picking factors (PPF) is the main objective. Therefore a HS based, LP optimization code is prepared and CITATION code which is a neutronic calculation code, applied to obtain effective multiplication factor, neutron fluxes and power density in desired cores. Using adaptive improved harmony search and neutronic code, generated LP optimization code, could be applicable for PWRs core with many numbers of FAs. In this work, at first step, HS and IHS efficiencies are compared with some other heuristic algorithms in Shekel's Foxholes problem and capability of the adaptive improved harmony search is demonstrated. Results show, efficient application of IHS. At second step, two WWER cases are studied and then IHS proffered improved core patterns with regard to mentioned objective functions.

  8. Radiation Enhances Regulatory T Cell Representation

    Energy Technology Data Exchange (ETDEWEB)

    Kachikwu, Evelyn L.; Iwamoto, Keisuke S.; Liao, Yu-Pei; DeMarco, John J.; Agazaryan, Nzhde [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Economou, James S. [Department of Surgical Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); McBride, William H. [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Schaue, Doerthe, E-mail: dschaue@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States)

    2011-11-15

    Purpose: Immunotherapy could be a useful adjunct to standard cytotoxic therapies such as radiation in patients with micrometastatic disease, although successful integration of immunotherapy into treatment protocols will require further understanding of how standard therapies affect the generation of antitumor immune responses. This study was undertaken to evaluate the impact of radiation therapy (RT) on immunosuppressive T regulatory (Treg) cells. Methods and Materials: Treg cells were identified as a CD4{sup +}CD25{sup hi}Foxp3{sup +} lymphocyte subset, and their fate was followed in a murine TRAMP C1 model of prostate cancer in mice with and without RT. Results: CD4{sup +}CD25{sup hi}Foxp3{sup +} Treg cells increased in immune organs after local leg or whole-body radiation. A large part, but not all, of this increase after leg-only irradiation could be ascribed to radiation scatter and Treg cells being intrinsically more radiation resistant than other lymphocyte subpopulations, resulting in their selection. Their functional activity on a per-cell basis was not affected by radiation exposure. Similar findings were made with mice receiving local RT to murine prostate tumors growing in the leg. The importance of the Treg cell population in the response to RT was shown by systemic elimination of Treg cells, which greatly enhanced radiation-induced tumor regression. Conclusions: We conclude that Treg cells are more resistant to radiation than other lymphocytes, resulting in their preferential increase. Treg cells may form an important homeostatic mechanism for tissues injured by radiation, and in a tumor context, they may assist in immune evasion during therapy. Targeting this population may allow enhancement of radiotherapeutic benefit through immune modulation.

  9. Radiation Enhances Regulatory T Cell Representation

    International Nuclear Information System (INIS)

    Kachikwu, Evelyn L.; Iwamoto, Keisuke S.; Liao, Yu-Pei; DeMarco, John J.; Agazaryan, Nzhde; Economou, James S.; McBride, William H.; Schaue, Dörthe

    2011-01-01

    Purpose: Immunotherapy could be a useful adjunct to standard cytotoxic therapies such as radiation in patients with micrometastatic disease, although successful integration of immunotherapy into treatment protocols will require further understanding of how standard therapies affect the generation of antitumor immune responses. This study was undertaken to evaluate the impact of radiation therapy (RT) on immunosuppressive T regulatory (Treg) cells. Methods and Materials: Treg cells were identified as a CD4 + CD25 hi Foxp3 + lymphocyte subset, and their fate was followed in a murine TRAMP C1 model of prostate cancer in mice with and without RT. Results: CD4 + CD25 hi Foxp3 + Treg cells increased in immune organs after local leg or whole-body radiation. A large part, but not all, of this increase after leg-only irradiation could be ascribed to radiation scatter and Treg cells being intrinsically more radiation resistant than other lymphocyte subpopulations, resulting in their selection. Their functional activity on a per-cell basis was not affected by radiation exposure. Similar findings were made with mice receiving local RT to murine prostate tumors growing in the leg. The importance of the Treg cell population in the response to RT was shown by systemic elimination of Treg cells, which greatly enhanced radiation-induced tumor regression. Conclusions: We conclude that Treg cells are more resistant to radiation than other lymphocytes, resulting in their preferential increase. Treg cells may form an important homeostatic mechanism for tissues injured by radiation, and in a tumor context, they may assist in immune evasion during therapy. Targeting this population may allow enhancement of radiotherapeutic benefit through immune modulation.

  10. An improved contrast enhancement algorithm for infrared images based on adaptive double plateaus histogram equalization

    Science.gov (United States)

    Li, Shuo; Jin, Weiqi; Li, Li; Li, Yiyang

    2018-05-01

    Infrared thermal images can reflect the thermal-radiation distribution of a particular scene. However, the contrast of the infrared images is usually low. Hence, it is generally necessary to enhance the contrast of infrared images in advance to facilitate subsequent recognition and analysis. Based on the adaptive double plateaus histogram equalization, this paper presents an improved contrast enhancement algorithm for infrared thermal images. In the proposed algorithm, the normalized coefficient of variation of the histogram, which characterizes the level of contrast enhancement, is introduced as feedback information to adjust the upper and lower plateau thresholds. The experiments on actual infrared images show that compared to the three typical contrast-enhancement algorithms, the proposed algorithm has better scene adaptability and yields better contrast-enhancement results for infrared images with more dark areas or a higher dynamic range. Hence, it has high application value in contrast enhancement, dynamic range compression, and digital detail enhancement for infrared thermal images.

  11. The Major Players in Adaptive Immunity-Cell-mediated Immunity

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 6. The Major Players in Adaptive Immunity - Cell-mediated Immunity. Asma Ahmed Banishree Saha Anand Patwardhan Shwetha Shivaprasad Dipankar Nandi. General Article Volume 14 Issue 6 June 2009 pp 610-621 ...

  12. Edge and line enhancement by adaptive lattice filtering

    International Nuclear Information System (INIS)

    Brolley, J.E.

    1979-01-01

    Digitized images have been two-dimensionally transformed to the Haar sequency domain. High-sequency boosting was performed and the inverse Haar two-dimensional transform applied. The resulting image was then raster-scanned with a continuously adaptive lattice filter. This procedure was applied to a simple image of a photographic step tablet and a complex scene. All of the lines of the step tablet were well defined over the whole dynamic range. Useful definition of lines in the complex scene was obtained

  13. Adaptative Peer to Peer Data Sharing for Technology Enhanced Learning

    Science.gov (United States)

    Angelaccio, Michele; Buttarazzi, Berta

    Starting from the hypothesis that P2P Data Sharing in a direct teaching scenario (e.g.: a classroom lesson) may lead to relevant benefits, this paper explores the features of EduSHARE a Collaborative Learning System useful for Enhanced Learning Process.

  14. Role of metabolic stress for enhancing muscle adaptations: Practical applications

    OpenAIRE

    de Freitas, Marcelo Conrado; Gerosa-Neto, Jose; Zanchi, Nelo Eidy; Lira, Fabio Santos; Rossi, Fabr?cio Eduardo

    2017-01-01

    Metabolic stress is a physiological process that occurs during exercise in response to low energy that leads to metabolite accumulation [lactate, phosphate inorganic (Pi) and ions of hydrogen (H+)] in muscle cells. Traditional exercise protocol (i.e., Resistance training) has an important impact on the increase of metabolite accumulation, which influences hormonal release, hypoxia, reactive oxygen species (ROS) production and cell swelling. Changes in acute exercise routines, such as intensit...

  15. Relation between radio-adaptive response and cell to cell communication

    International Nuclear Information System (INIS)

    Keiichiro Ishii

    1996-01-01

    Ionizing radiation has been considered to cause severe damages to DNA and do harm to cells in proportion to the dose, however low it might be. In 1984, Wolff et al. showed that human peripheral lymphocytes adapted to the low-dose radiation from 3 H-TdR added in culture medium and became resistant to the subsequent irradiation with high-doses of X-rays. This response, which is called radio-adaptive response, is also induced by X-rays and gamma-rays in human lymphocytes and Chinese hamster V79 cells. However, the mechanisms of and conditions for adaptive responses to radiation have not been clarified. With an objective of clarifying the conditions for adaptive responses of cells to radiation, we examined how the cell to cell communication is involved in the adaptive responses. We irradiated normal human embryo-derived (HE) cells and cancer cells (HeLa) in culture at high density with low-dose X-ray and examined their radio-adaptive responses by measuring the changes in sensitivity to subsequent high-dose X-ray irradiation using the Trypan Blue dye-exclusion test method. We also conducted experiments to examine the effects of Ca 2+ ions and Phorbol 12-Myristate 13-Acetate (TPA) which are supposed to be involved in cell to cell communication. (author)

  16. Low-Light Image Enhancement Using Adaptive Digital Pixel Binning

    Directory of Open Access Journals (Sweden)

    Yoonjong Yoo

    2015-06-01

    Full Text Available This paper presents an image enhancement algorithm for low-light scenes in an environment with insufficient illumination. Simple amplification of intensity exhibits various undesired artifacts: noise amplification, intensity saturation, and loss of resolution. In order to enhance low-light images without undesired artifacts, a novel digital binning algorithm is proposed that considers brightness, context, noise level, and anti-saturation of a local region in the image. The proposed algorithm does not require any modification of the image sensor or additional frame-memory; it needs only two line-memories in the image signal processor (ISP. Since the proposed algorithm does not use an iterative computation, it can be easily embedded in an existing digital camera ISP pipeline containing a high-resolution image sensor.

  17. Radiation adaptive response for the growth of cultured glial cells

    International Nuclear Information System (INIS)

    Suzuki, S.; Miura, Y.; Kano, M.; Toda, T.; Urano, S.

    2003-01-01

    Full text: To examine the molecular mechanism of radiation adaptive response (RAR) for the growth of cultured glial cells and to investigate the influence of aging on the response, glial cells were cultured from young and aged rats (1 month and 24 months old). RAR for the growth of glial cells conditioned with a low dose of X-rays and subsequently exposed to a high dose of X-rays was examined for cell number and BrdU incorporation. Involvement of the subcellular signaling pathway factors in RAR was investigated using their inhibitors, activators and mutated glial cells. RAR was observed in cells cultured from young rats, but was not in cells from aged rats. The inhibitors of protein kinase C (PKC) and DNA-dependent protein kinase (DNA-PK) or phosphatidylinositol 3-kinase (PI3K) suppressed RAR. The activators of PKC instead of low dose irradiation also caused RAR. Moreover, glial cells cultured from severe combined immunodeficiency (scid) mice (CB-17 scid) and ataxia-telangiectasia (AT) cells from AT patients showed no RAR. These results indicated that PKC, ATM, DNAPK and/or PI3K were involved in RAR for growth and BrdU incorporation of cultured glial cells and RAR decreased with aging. Proteomics data of glial cells exposed to severe stress of H 2 O 2 or X-rays also will be presented in the conference since little or no difference has not been observed with slight stress yet

  18. Biotin deficiency enhances the inflammatory response of human dendritic cells.

    Science.gov (United States)

    Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

    2016-09-01

    The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

  19. Bmi-1 confers adaptive radioresistance to KYSE-150R esophageal carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Guanyu [Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Liu, Luying [Department of Radiotherapy, Zhejiang Cancer Hospital, Hangzhou (China); Sharma, Sherven [David Geffen School of Medicine at UCLA, and the Department of Veterans Affairs, Los Angeles, CA (United States); Liu, Hai; Yang, Weifang; Sun, Xiaonan [Department of Radiotherapy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Dong, Qinghua, E-mail: dongqinghua@zju.edu.cn [Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou (China)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Adaptive radioresistant KYSE-150R cells expressed high level of Bmi-1. Black-Right-Pointing-Pointer Bmi-1 depletion sensitized KYSE-150R cells to RT. Black-Right-Pointing-Pointer Bmi-1 depletion increased the generation of ROS in KYSE-150R cells exposed to radiation. Black-Right-Pointing-Pointer Bmi-1 depletion impaired DNA repair capacities in KYSE-150R cells exposed to radiation. -- Abstract: Radiotherapy (RT) is a major modality of cancer treatment. However, tumors often acquire radioresistance, which causes RT to fail. The exact mechanisms by which tumor cells subjected to fractionated irradiation (FIR) develop an adaptive radioresistance are largely unknown. Using the radioresistant KYSE-150R esophageal squamous cell carcinoma (ESCC) model, which was derived from KYSE-150 parental cells using FIR, the role of Bmi-1 in mediating the radioadaptive response of ESCC cells to RT was investigated. The results showed that the level of Bmi-1 expression was significantly higher in KYSE-150R cells than in the KYSE-150 parental cells. Bmi-1 depletion sensitized the KYSE-150R cells to RT mainly through the induction of apoptosis, partly through the induction of senescence. A clonogenic cell survival assay showed that Bmi-1 depletion significantly decreased the radiation survival fraction in KYSE-150R cells. Furthermore, Bmi-1 depletion increased the generation of reactive oxygen species (ROS) and the expression of oxidase genes (Lpo, Noxo1 and Alox15) in KYSE-150R cells exposed to irradiation. DNA repair capacities assessed by {gamma}-H2AX foci formation were also impaired in the Bmi-1 down-regulated KYSE-150R cells. These results suggest that Bmi-1 plays an important role in tumor radioadaptive resistance under FIR and may be a potent molecular target for enhancing the efficacy of fractionated RT.

  20. The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development.

    Science.gov (United States)

    Miyazaki, Masaki; Miyazaki, Kazuko; Chen, Kenian; Jin, Yi; Turner, Jacob; Moore, Amanda J; Saito, Rintaro; Yoshida, Kenichi; Ogawa, Seishi; Rodewald, Hans-Reimer; Lin, Yin C; Kawamoto, Hiroshi; Murre, Cornelis

    2017-05-16

    Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling. E2A and HEB acted in ETPs to establish and maintain a T-cell-lineage-specific enhancer repertoire, including regulatory elements associated with the Notch1, Rag1, and Rag2 loci. On the basis of these and previous observations, we propose that the E-Id protein axis specifies innate and adaptive lymphoid cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Efficiency Enhancement of Silicon Solar Cells by Porous Silicon Technology

    Directory of Open Access Journals (Sweden)

    Eugenijus SHATKOVSKIS

    2012-09-01

    Full Text Available Silicon solar cells produced by a usual technology in p-type, crystalline silicon wafer were investigated. The manufactured solar cells were of total thickness 450 mm, the junction depth was of 0.5 mm – 0.7 mm. Porous silicon technologies were adapted to enhance cell efficiency. The production of porous silicon layer was carried out in HF: ethanol = 1 : 2 volume ratio electrolytes, illuminating by 50 W halogen lamps at the time of processing. The etching current was computer-controlled in the limits of (6 ÷ 14 mA/cm2, etching time was set in the interval of (10 ÷ 20 s. The characteristics and performance of the solar cells samples was carried out illuminating by Xenon 5000 K lamp light. Current-voltage characteristic studies have shown that porous silicon structures produced affect the extent of dark and lighting parameters of the samples. Exactly it affects current-voltage characteristic and serial resistance of the cells. It has shown, the formation of porous silicon structure causes an increase in the electric power created of solar cell. Conversion efficiency increases also respectively to the initial efficiency of cell. Increase of solar cell maximum power in 15 or even more percent is found. The highest increase in power have been observed in the spectral range of Dl @ (450 ÷ 850 nm, where ~ 60 % of the A1.5 spectra solar energy is located. It has been demonstrated that porous silicon technology is effective tool to improve the silicon solar cells performance.DOI: http://dx.doi.org/10.5755/j01.ms.18.3.2428

  2. Symmetric vs. asymmetric stem cell divisions: an adaptation against cancer?

    Directory of Open Access Journals (Sweden)

    Leili Shahriyari

    Full Text Available Traditionally, it has been held that a central characteristic of stem cells is their ability to divide asymmetrically. Recent advances in inducible genetic labeling provided ample evidence that symmetric stem cell divisions play an important role in adult mammalian homeostasis. It is well understood that the two types of cell divisions differ in terms of the stem cells' flexibility to expand when needed. On the contrary, the implications of symmetric and asymmetric divisions for mutation accumulation are still poorly understood. In this paper we study a stochastic model of a renewing tissue, and address the optimization problem of tissue architecture in the context of mutant production. Specifically, we study the process of tumor suppressor gene inactivation which usually takes place as a consequence of two "hits", and which is one of the most common patterns in carcinogenesis. We compare and contrast symmetric and asymmetric (and mixed stem cell divisions, and focus on the rate at which double-hit mutants are generated. It turns out that symmetrically-dividing cells generate such mutants at a rate which is significantly lower than that of asymmetrically-dividing cells. This result holds whether single-hit (intermediate mutants are disadvantageous, neutral, or advantageous. It is also independent on whether the carcinogenic double-hit mutants are produced only among the stem cells or also among more specialized cells. We argue that symmetric stem cell divisions in mammals could be an adaptation which helps delay the onset of cancers. We further investigate the question of the optimal fraction of stem cells in the tissue, and quantify the contribution of non-stem cells in mutant production. Our work provides a hypothesis to explain the observation that in mammalian cells, symmetric patterns of stem cell division seem to be very common.

  3. Epigenetic stability, adaptability, and reversibility in human embryonic stem cells

    OpenAIRE

    Tompkins, Joshua D.; Hall, Christine; Chen, Vincent Chang-yi; Li, Arthur Xuejun; Wu, Xiwei; Hsu, David; Couture, Larry A.; Riggs, Arthur D.

    2012-01-01

    The stability of human embryonic stem cells (hESCs) is of critical importance for both experimental and clinical applications. We find that as an initial response to altered culture conditions, hESCs change their transcription profile for hundreds of genes and their DNA methylation profiles for several genes outside the core pluripotency network. After adaption to conditions of feeder-free defined and/or xeno-free culture systems, expression and DNA methylation profiles are quite stable for a...

  4. Adapting hypertension self-management interventions to enhance their sustained effectiveness among urban African Americans.

    Science.gov (United States)

    Ameling, Jessica M; Ephraim, Patti L; Bone, Lee R; Levine, David M; Roter, Debra L; Wolff, Jennifer L; Hill-Briggs, Felicia; Fitzpatrick, Stephanie L; Noronha, Gary J; Fagan, Peter J; Lewis-Boyer, LaPricia; Hickman, Debra; Simmons, Michelle; Purnell, Leon; Fisher, Annette; Cooper, Lisa A; Aboumatar, Hanan J; Albert, Michael C; Flynn, Sarah J; Boulware, L Ebony

    2014-01-01

    African Americans suffer disproportionately poor hypertension control despite the availability of efficacious interventions. Using principles of community-based participatory research and implementation science, we adapted established hypertension self-management interventions to enhance interventions' cultural relevance and potential for sustained effectiveness among urban African Americans. We obtained input from patients and their family members, their health care providers, and community members. The process required substantial time and resources, and the adapted interventions will be tested in a randomized controlled trial.

  5. Adapting Hypertension Self-Management Interventions to Enhance their Sustained Effectiveness among Urban African Americans

    Science.gov (United States)

    Ameling, Jessica M.; Ephraim, Patti L.; Bone, Lee R.; Levine, David M.; Roter, Debra L.; Wolff, Jennifer L.; Hill-Briggs, Felicia; Fitzpatrick, Stephanie L.; Noronha, Gary J.; Fagan, Peter J.; Lewis-Boyer, LaPricia; Hickman, Debra; Simmons, Michelle; Purnell, Leon; Fisher, Annette; Cooper, Lisa A.; Aboumatar, Hanan J.; Albert, Michael C.; Flynn, Sarah J.; Boulware, L. Ebony

    2014-01-01

    African Americans suffer disproportionately poor hypertension control despite the availability of efficacious interventions. Using principles of community-based participatory research and implementation science, we adapted established hypertension self-management interventions to enhance interventions’ cultural relevance and potential for sustained effectiveness among urban African Americans. We obtained input from patients and their family members, their health care providers, and community members. The process required substantial time and resources, and the adapted interventions will be tested in a randomized controlled trial. PMID:24569158

  6. An Adaptive Image Enhancement Technique by Combining Cuckoo Search and Particle Swarm Optimization Algorithm

    Directory of Open Access Journals (Sweden)

    Zhiwei Ye

    2015-01-01

    Full Text Available Image enhancement is an important procedure of image processing and analysis. This paper presents a new technique using a modified measure and blending of cuckoo search and particle swarm optimization (CS-PSO for low contrast images to enhance image adaptively. In this way, contrast enhancement is obtained by global transformation of the input intensities; it employs incomplete Beta function as the transformation function and a novel criterion for measuring image quality considering three factors which are threshold, entropy value, and gray-level probability density of the image. The enhancement process is a nonlinear optimization problem with several constraints. CS-PSO is utilized to maximize the objective fitness criterion in order to enhance the contrast and detail in an image by adapting the parameters of a novel extension to a local enhancement technique. The performance of the proposed method has been compared with other existing techniques such as linear contrast stretching, histogram equalization, and evolutionary computing based image enhancement methods like backtracking search algorithm, differential search algorithm, genetic algorithm, and particle swarm optimization in terms of processing time and image quality. Experimental results demonstrate that the proposed method is robust and adaptive and exhibits the better performance than other methods involved in the paper.

  7. An adaptive image enhancement technique by combining cuckoo search and particle swarm optimization algorithm.

    Science.gov (United States)

    Ye, Zhiwei; Wang, Mingwei; Hu, Zhengbing; Liu, Wei

    2015-01-01

    Image enhancement is an important procedure of image processing and analysis. This paper presents a new technique using a modified measure and blending of cuckoo search and particle swarm optimization (CS-PSO) for low contrast images to enhance image adaptively. In this way, contrast enhancement is obtained by global transformation of the input intensities; it employs incomplete Beta function as the transformation function and a novel criterion for measuring image quality considering three factors which are threshold, entropy value, and gray-level probability density of the image. The enhancement process is a nonlinear optimization problem with several constraints. CS-PSO is utilized to maximize the objective fitness criterion in order to enhance the contrast and detail in an image by adapting the parameters of a novel extension to a local enhancement technique. The performance of the proposed method has been compared with other existing techniques such as linear contrast stretching, histogram equalization, and evolutionary computing based image enhancement methods like backtracking search algorithm, differential search algorithm, genetic algorithm, and particle swarm optimization in terms of processing time and image quality. Experimental results demonstrate that the proposed method is robust and adaptive and exhibits the better performance than other methods involved in the paper.

  8. An Image Enhancement Method Using the Quantum-Behaved Particle Swarm Optimization with an Adaptive Strategy

    Directory of Open Access Journals (Sweden)

    Xiaoping Su

    2013-01-01

    Full Text Available Image enhancement techniques are very important to image processing, which are used to improve image quality or extract the fine details in degraded images. In this paper, two novel objective functions based on the normalized incomplete Beta transform function are proposed to evaluate the effectiveness of grayscale image enhancement and color image enhancement, respectively. Using these objective functions, the parameters of transform functions are estimated by the quantum-behaved particle swarm optimization (QPSO. We also propose an improved QPSO with an adaptive parameter control strategy. The QPSO and the AQPSO algorithms, along with genetic algorithm (GA and particle swarm optimization (PSO, are tested on several benchmark grayscale and color images. The results show that the QPSO and AQPSO perform better than GA and PSO for the enhancement of these images, and the AQPSO has some advantages over QPSO due to its adaptive parameter control strategy.

  9. Improvement of observer performance during fluoroscopy by local adaptive contrast enhancement

    International Nuclear Information System (INIS)

    Gould, R.G.; Demas, B.E.; Maroney, T.P.

    1988-01-01

    The ability of a video processor (FluoroVision FV-1), which performs two-dimensional locally adaptive contrast enhancement, to improve the detection of a low-contrast object was evaluated by means of receiver operating characteristic (ROC) curves. Three independent observers viewed a videotape of 50 fluoroscopic images of a varied background, in which a test object was present in 25. Each observer viewed the tape under four conditions: (1) no processing, (2) temporal noise reduction (gaussian weighted time averaging, (3) contrast enhancement, and (4) both noise reduction and contrast enhancement. The results were that detection was significantly improved by the locally adaptive contrast enhancement. Noise reduction did not significantly improve performance, probably because washer detection was limited by background contrast variations as well as noise and because only a small amount of noise reduction was used. The authors conclude that the processing device is potentially valuable in improving the quality of clinical fluoroscopic images

  10. Shielding analysis of the IEM cell offset adapter plate

    International Nuclear Information System (INIS)

    Simons, R.L.

    1995-01-01

    The adapter plate for the Interim Examination and Maintenance (IEM) cell ten foot ceiling valve was modified so that the penetration through the valve is offset to the north side of the steel plate. The modifications required that the shielding effectiveness be evaluated for several operating conditions. The highest gamma ray dose rate (51 mrem/hr) occurs when a Core Component Container (CCC) with six high burn-up driver fuel assemblies is transferred into or out of Solid Waste Cask (SWC). The neutron dose rate at the same source location is 2.5 mrem/hr. The total dose rate during the transfer is less than the 200 mrem/hr limit. If the ten foot ceiling valve is closed, the dose rate with twelve DFA in the cell will be less than 0.1 mrem/hr. However, with the ceiling valve open the dose rate will be as high as 12 mrem/hr. The latter condition will require controlled access to the area around the offset adapter plate when the ceiling valve is open. It was found that gaps in the shield block around the SWC floor valve will allow contact dose rates as high as 350 mrem/hr during the transfer of a fully loaded CCC. Although this situation does not pertain to the offset adapter plate, it will require controlled access around the SWC valve during the transfer of a fully loaded CCC

  11. Direct Adaptive Aircraft Control Using Dynamic Cell Structure Neural Networks

    Science.gov (United States)

    Jorgensen, Charles C.

    1997-01-01

    A Dynamic Cell Structure (DCS) Neural Network was developed which learns topology representing networks (TRNS) of F-15 aircraft aerodynamic stability and control derivatives. The network is integrated into a direct adaptive tracking controller. The combination produces a robust adaptive architecture capable of handling multiple accident and off- nominal flight scenarios. This paper describes the DCS network and modifications to the parameter estimation procedure. The work represents one step towards an integrated real-time reconfiguration control architecture for rapid prototyping of new aircraft designs. Performance was evaluated using three off-line benchmarks and on-line nonlinear Virtual Reality simulation. Flight control was evaluated under scenarios including differential stabilator lock, soft sensor failure, control and stability derivative variations, and air turbulence.

  12. AN ILLUMINATION INVARIANT FACE RECOGNITION BY ENHANCED CONTRAST LIMITED ADAPTIVE HISTOGRAM EQUALIZATION

    Directory of Open Access Journals (Sweden)

    A. Thamizharasi

    2016-05-01

    Full Text Available Face recognition system is gaining more importance in social networks and surveillance. The face recognition task is complex due to the variations in illumination, expression, occlusion, aging and pose. The illumination variations in image are due to changes in lighting conditions, poor illumination, low contrast or increased brightness. The variations in illumination adversely affect the quality of image and recognition accuracy. The illumination variations in face image have to be pre-processed prior to face recognition. The Contrast Limited Adaptive Histogram Equalization (CLAHE is an image enhancement technique popular in enhancing medical images. The proposed work is to create illumination invariant face recognition system by enhancing Contrast Limited Adaptive Histogram Equalization technique. This method is termed as “Enhanced CLAHE”. The efficiency of Enhanced CLAHE is tested using Fuzzy K Nearest Neighbour classifier and fisher face subspace projection method. The face recognition accuracy percentage rate, Equal Error Rate and False Acceptance Rate at 1% are calculated. The performance of CLAHE and Enhanced CLAHE methods is compared. The efficiency of the Enhanced CLAHE method is tested with three public face databases AR, Yale and ORL. The Enhanced CLAHE has very high recognition accuracy percentage rate when compared to CLAHE.

  13. Can Survival Processing Enhance Story Memory? Testing the Generalizability of the Adaptive Memory Framework

    Science.gov (United States)

    Seamon, John G.; Bohn, Justin M.; Coddington, Inslee E.; Ebling, Maritza C.; Grund, Ethan M.; Haring, Catherine T.; Jang, Sue-Jung; Kim, Daniel; Liong, Christopher; Paley, Frances M.; Pang, Luke K.; Siddique, Ashik H.

    2012-01-01

    Research from the adaptive memory framework shows that thinking about words in terms of their survival value in an incidental learning task enhances their free recall relative to other semantic encoding strategies and intentional learning (Nairne, Pandeirada, & Thompson, 2008). We found similar results. When participants used incidental…

  14. An interdisciplinary approach to identify adaptation strategies that enhance flood resilience and urban liveability

    DEFF Research Database (Denmark)

    Rogers, B. C.; Bertram, N.; Gunn, Alex

    This paper provides guidance on how to identify and design the most suitable climate adaptation strategies for enhancing the liveability and flood resilience of urban catchments. It presents findings from a case study of Elwood, a coastal Melbourne suburb regularly affected by flooding. The resea...

  15. Adapting Hypertension Self-Management Interventions to Enhance their Sustained Effectiveness among Urban African Americans

    OpenAIRE

    Ameling, Jessica M.; Ephraim, Patti L.; Bone, Lee R.; Levine, David M.; Roter, Debra L.; Wolff, Jennifer L.; Hill-Briggs, Felicia; Fitzpatrick, Stephanie L.; Noronha, Gary J.; Fagan, Peter J.; Lewis-Boyer, LaPricia; Hickman, Debra; Simmons, Michelle; Purnell, Leon; Fisher, Annette

    2014-01-01

    African Americans suffer disproportionately poor hypertension control despite the availability of efficacious interventions. Using principles of community-based participatory research and implementation science, we adapted established hypertension self-management interventions to enhance interventions’ cultural relevance and potential for sustained effectiveness among urban African Americans. We obtained input from patients and their family members, their health care providers, and community ...

  16. Non-adaptive and adaptive hybrid approaches for enhancing water quality management

    Science.gov (United States)

    Kalwij, Ineke M.; Peralta, Richard C.

    2008-09-01

    SummaryUsing optimization to help solve groundwater management problems cost-effectively is becoming increasingly important. Hybrid optimization approaches, that combine two or more optimization algorithms, will become valuable and common tools for addressing complex nonlinear hydrologic problems. Hybrid heuristic optimizers have capabilities far beyond those of a simple genetic algorithm (SGA), and are continuously improving. SGAs having only parent selection, crossover, and mutation are inefficient and rarely used for optimizing contaminant transport management. Even an advanced genetic algorithm (AGA) that includes elitism (to emphasize using the best strategies as parents) and healing (to help assure optimal strategy feasibility) is undesirably inefficient. Much more efficient than an AGA is the presented hybrid (AGCT), which adds comprehensive tabu search (TS) features to an AGA. TS mechanisms (TS probability, tabu list size, search coarseness and solution space size, and a TS threshold value) force the optimizer to search portions of the solution space that yield superior pumping strategies, and to avoid reproducing similar or inferior strategies. An AGCT characteristic is that TS control parameters are unchanging during optimization. However, TS parameter values that are ideal for optimization commencement can be undesirable when nearing assumed global optimality. The second presented hybrid, termed global converger (GC), is significantly better than the AGCT. GC includes AGCT plus feedback-driven auto-adaptive control that dynamically changes TS parameters during run-time. Before comparing AGCT and GC, we empirically derived scaled dimensionless TS control parameter guidelines by evaluating 50 sets of parameter values for a hypothetical optimization problem. For the hypothetical area, AGCT optimized both well locations and pumping rates. The parameters are useful starting values because using trial-and-error to identify an ideal combination of control

  17. Divergent Roles of Interferon-γ and Innate Lymphoid Cells in Innate and Adaptive Immune Cell-Mediated Intestinal Inflammation.

    Science.gov (United States)

    Brasseit, Jennifer; Kwong Chung, Cheong K C; Noti, Mario; Zysset, Daniel; Hoheisel-Dickgreber, Nina; Genitsch, Vera; Corazza, Nadia; Mueller, Christoph

    2018-01-01

    Aberrant interferon gamma (IFNγ) expression is associated with the pathogenesis of numerous autoimmune- and inflammatory disorders, including inflammatory bowel diseases (IBD). However, the requirement of IFNγ for the pathogenesis of chronic intestinal inflammation remains controversial. The aim of this study was thus to investigate the role of IFNγ in experimental mouse models of innate and adaptive immune cell-mediated intestinal inflammation using genetically and microbiota-stabilized hosts. While we find that IFNγ drives acute intestinal inflammation in the anti-CD40 colitis model in an innate lymphoid cell (ILC)-dependent manner, IFNγ secreted by both transferred CD4 T cells and/or cells of the lymphopenic Rag1 -/- recipient mice was dispensable for CD4 T cell-mediated colitis. In the absence of IFNγ, intestinal inflammation in CD4 T cell recipient mice was associated with enhanced IL17 responses; consequently, targeting IL17 signaling in IFNγ-deficient mice reduced T cell-mediated colitis. Intriguingly, in contrast to the anti-CD40 model of colitis, depletion of ILC in the Rag1 -/- recipients of colitogenic CD4 T cells did not prevent induction of colonic inflammation. Together, our findings demonstrate that IFNγ represents an essential, or a redundant, pro-inflammatory cytokine for the induction of intestinal inflammation, depending on the experimental mouse model used and on the nature of the critical disease inducing immune cell populations involved.

  18. Spatial consequences of bleaching adaptation in cat retinal ganglion cells.

    Science.gov (United States)

    Bonds, A B; Enroth-Cugell, C

    1981-01-01

    1. Experiments were conducted to study the effects of localized bleaching on the centre responses of rod-driven cat retinal ganglion cells. 2. Stimulation as far as 2 degrees from the bleaching site yielded responses which were reduced nearly as much as those generated at the bleaching site. Bleaching in the receptive field middle reduced responsiveness at a site 1 degrees peripheral more than bleaching at that peripheral site itself. 3. The effectiveness of a bleach in reducing centre responsiveness is related to the sensitivity of the region in which the bleach is applied. 4. Response reduction after a 0.2 degree bleach followed the same temporal pattern for concentric test spots of from 0.2 to 1.8 degrees in diameter, implying a substantially uniform spread of adaptation within these bounds. 5. A linear trade-off between fraction of rhodopsin and area bleached over a range of 8:1 yields the same pattern of response reduction, implying that the non-linear nature of bleaching adaptation is a property of the adaptation pool rather than independent photoreceptors. PMID:7320894

  19. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Hamada, Shin; Masamune, Atsushi; Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa; Hamada, Hirofumi; Kobune, Masayoshi; Satoh, Kennichi; Shimosegawa, Tooru

    2012-01-01

    Highlights: ► Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. ► Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. ► Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. ► Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. ► This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called “cancer stem cells”, within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the “stemness” of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

  20. Review: Natural killer cells enhance the immune surveillance of ...

    African Journals Online (AJOL)

    All the cells of the immune system cooperatively work against infectious agents and cancerous cells but Natural killer (NK) cells are playing an important role to respond to tumor by enhancing the expression of complementary domain (CD86) on dendritic cells (DCs) and production of IL-12. NK cells demolished tumor ...

  1. The local enhancement conundrum: in search of the adaptive value of a social learning mechanism.

    Science.gov (United States)

    Arbilly, Michal; Laland, Kevin N

    2014-02-01

    Social learning mechanisms are widely thought to vary in their degree of complexity as well as in their prevalence in the natural world. While learning the properties of a stimulus that generalize to similar stimuli at other locations (stimulus enhancement) prima facie appears more useful to an animal than learning about a specific stimulus at a specific location (local enhancement), empirical evidence suggests that the latter is much more widespread in nature. Simulating populations engaged in a producer-scrounger game, we sought to deploy mathematical models to identify the adaptive benefits of reliance on local enhancement and/or stimulus enhancement, and the alternative conditions favoring their evolution. Surprisingly, we found that while stimulus enhancement readily evolves, local enhancement is advantageous only under highly restricted conditions: when generalization of information was made unreliable or when error in social learning was high. Our results generate a conundrum over how seemingly conflicting empirical and theoretical findings can be reconciled. Perhaps the prevalence of local enhancement in nature is due to stimulus enhancement costs independent of the learning task itself (e.g. predation risk), perhaps natural habitats are often characterized by unreliable yet highly rewarding payoffs, or perhaps local enhancement occurs less frequently, and stimulus enhancement more frequently, than widely believed. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation

    Directory of Open Access Journals (Sweden)

    Sara Calafate

    2015-05-01

    Full Text Available Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer’s disease (AD. Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  3. Evolutionary Adaptation of Kluyveromyces marxianus NIRE-K3 for Enhanced Xylose Utilization

    International Nuclear Information System (INIS)

    Sharma, Nilesh Kumar; Behera, Shuvashish; Arora, Richa; Kumar, Sachin

    2017-01-01

    The evolutionary adaptation was approached on the thermotolerant yeast Kluyveromyces marxianus NIRE-K3 at 45°C on xylose as a sole source of carbon for enhancement of xylose uptake. After 60 cycles, evolved strain K. marxianus NIRE-K3.1 showed comparatively 3.75- and 3.0-fold higher specific growth and xylose uptake rates, respectively, than that of native strain. Moreover, the short lag phase was also observed on adapted strain. During batch fermentation with xylose concentration of 30 g l −1 , K. marxianus NIRE-K3.1 could utilize about 96% of xylose in 72 h and produced 4.67 and 15.7 g l −1 of ethanol and xylitol, respectively, which were 9.72- and 4.63-fold higher than that of native strain. Similarly, specific sugar consumption rate, xylitol, and ethanol yields were 5.07-, 1.15-, and 2.44-fold higher as compared to the native strain, respectively. The results obtained after evolutionary adaptation of K. marxianus NIRE-K3 show the significant improvement in the xylose utilization, ethanol and xylitol yields, and productivities. By understanding the results obtained, the significance of evolutionary adaptation has been rationalized, since the adapted culture could be more stable and could enhance the productivity.

  4. Evolutionary Adaptation of Kluyveromyces marxianus NIRE-K3 for Enhanced Xylose Utilization

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Nilesh Kumar [Biochemical Conversion Division, Sardar Swaran Singh National Institute of Bio-Energy, Kapurthala (India); I. K. Gujral Punjab Technical University, Kapurthala (India); Behera, Shuvashish; Arora, Richa; Kumar, Sachin, E-mail: sachin.biotech@gmail.com [Biochemical Conversion Division, Sardar Swaran Singh National Institute of Bio-Energy, Kapurthala (India)

    2017-12-12

    The evolutionary adaptation was approached on the thermotolerant yeast Kluyveromyces marxianus NIRE-K3 at 45°C on xylose as a sole source of carbon for enhancement of xylose uptake. After 60 cycles, evolved strain K. marxianus NIRE-K3.1 showed comparatively 3.75- and 3.0-fold higher specific growth and xylose uptake rates, respectively, than that of native strain. Moreover, the short lag phase was also observed on adapted strain. During batch fermentation with xylose concentration of 30 g l{sup −1}, K. marxianus NIRE-K3.1 could utilize about 96% of xylose in 72 h and produced 4.67 and 15.7 g l{sup −1} of ethanol and xylitol, respectively, which were 9.72- and 4.63-fold higher than that of native strain. Similarly, specific sugar consumption rate, xylitol, and ethanol yields were 5.07-, 1.15-, and 2.44-fold higher as compared to the native strain, respectively. The results obtained after evolutionary adaptation of K. marxianus NIRE-K3 show the significant improvement in the xylose utilization, ethanol and xylitol yields, and productivities. By understanding the results obtained, the significance of evolutionary adaptation has been rationalized, since the adapted culture could be more stable and could enhance the productivity.

  5. Nck adapter proteins: functional versatility in T cells

    Directory of Open Access Journals (Sweden)

    Janssen Ottmar

    2009-02-01

    Full Text Available Abstract Nck is a ubiquitously expressed adapter protein that is almost exclusively built of one SH2 domain and three SH3 domains. The two isoproteins of Nck are functionally redundant in many aspects and differ in only few amino acids that are mostly located in the linker regions between the interaction modules. Nck proteins connect receptor and non-receptor tyrosine kinases to the machinery of actin reorganisation. Thereby, Nck regulates activation-dependent processes during cell polarisation and migration and plays a crucial role in the signal transduction of a variety of receptors including for instance PDGF-, HGF-, VEGF- and Ephrin receptors. In most cases, the SH2 domain mediates binding to the phosphorylated receptor or associated phosphoproteins, while SH3 domain interactions lead to the formation of larger protein complexes. In T lymphocytes, Nck plays a pivotal role in the T cell receptor (TCR-induced reorganisation of the actin cytoskeleton and the formation of the immunological synapse. However, in this context, two different mechanisms and adapter complexes are discussed. In the first scenario, dependent on an activation-induced conformational change in the CD3ε subunits, a direct binding of Nck to components of the TCR/CD3 complex was shown. In the second scenario, Nck is recruited to the TCR complex via phosphorylated Slp76, another central constituent of the membrane proximal activation complex. Over the past years, a large number of putative Nck interactors have been identified in different cellular systems that point to diverse additional functions of the adapter protein, e.g. in the control of gene expression and proliferation.

  6. Adaptive Filtering to Enhance Noise Immunity of Impedance and Admittance Spectroscopy: Comparison with Fourier Transformation

    Science.gov (United States)

    Stupin, Daniil D.; Koniakhin, Sergei V.; Verlov, Nikolay A.; Dubina, Michael V.

    2017-05-01

    The time-domain technique for impedance spectroscopy consists of computing the excitation voltage and current response Fourier images by fast or discrete Fourier transformation and calculating their relation. Here we propose an alternative method for excitation voltage and current response processing for deriving a system impedance spectrum based on a fast and flexible adaptive filtering method. We show the equivalence between the problem of adaptive filter learning and deriving the system impedance spectrum. To be specific, we express the impedance via the adaptive filter weight coefficients. The noise-canceling property of adaptive filtering is also justified. Using the RLC circuit as a model system, we experimentally show that adaptive filtering yields correct admittance spectra and elements ratings in the high-noise conditions when the Fourier-transform technique fails. Providing the additional sensitivity of impedance spectroscopy, adaptive filtering can be applied to otherwise impossible-to-interpret time-domain impedance data. The advantages of adaptive filtering are justified with practical living-cell impedance measurements.

  7. Sealing Clay Text Segmentation Based on Radon-Like Features and Adaptive Enhancement Filters

    Directory of Open Access Journals (Sweden)

    Xia Zheng

    2015-01-01

    Full Text Available Text extraction is a key issue in sealing clay research. The traditional method based on rubbings increases the risk of sealing clay damage and is unfavorable to sealing clay protection. Therefore, using digital image of sealing clay, a new method for text segmentation based on Radon-like features and adaptive enhancement filters is proposed in this paper. First, adaptive enhancement LM filter bank is used to get the maximum energy image; second, the edge image of the maximum energy image is calculated; finally, Radon-like feature images are generated by combining maximum energy image and its edge image. The average image of Radon-like feature images is segmented by the image thresholding method. Compared with 2D Otsu, GA, and FastFCM, the experiment result shows that this method can perform better in terms of accuracy and completeness of the text.

  8. Enhancing the Ductility of Laser-Welded Copper-Aluminum Connections by using Adapted Filler Materials

    Science.gov (United States)

    Weigl, M.; Albert, F.; Schmidt, M.

    Laser micro welding of direct copper-aluminum connections typically leads to the formation of intermetallic phases and an embrittlement of the metal joints. By means of adapted filler materials it is possible to reduce the brittle phases and thereby enhance the ductility of these dissimilar connections. As the element silicon features quite a well compatibility with copper and aluminum, filler materials based on Al-Si and Cu-Si alloys are used in the current research studies. In contrast to direct Cu-Al welds, the aluminum filler alloy AlSi12 effectuates a more uniform element mixture and a significantly enhanced ductility.

  9. Bystander cells enhance NK cytotoxic efficiency by reducing search time.

    Science.gov (United States)

    Zhou, Xiao; Zhao, Renping; Schwarz, Karsten; Mangeat, Matthieu; Schwarz, Eva C; Hamed, Mohamed; Bogeski, Ivan; Helms, Volkhard; Rieger, Heiko; Qu, Bin

    2017-03-13

    Natural killer (NK) cells play a central role during innate immune responses by eliminating pathogen-infected or tumorigenic cells. In the microenvironment, NK cells encounter not only target cells but also other cell types including non-target bystander cells. The impact of bystander cells on NK killing efficiency is, however, still elusive. In this study we show that the presence of bystander cells, such as P815, monocytes or HUVEC, enhances NK killing efficiency. With bystander cells present, the velocity and persistence of NK cells were increased, whereas the degranulation of lytic granules remained unchanged. Bystander cell-derived H 2 O 2 was found to mediate the acceleration of NK cell migration. Using mathematical diffusion models, we confirm that local acceleration of NK cells in the vicinity of bystander cells reduces their search time to locate target cells. In addition, we found that integrin β chains (β1, β2 and β7) on NK cells are required for bystander-enhanced NK migration persistence. In conclusion, we show that acceleration of NK cell migration in the vicinity of H 2 O 2 -producing bystander cells reduces target cell search time and enhances NK killing efficiency.

  10. Responses of crayfish photoreceptor cells following intense light adaptation.

    Science.gov (United States)

    Cummins, D R; Goldsmith, T H

    1986-01-01

    After intense orange adapting exposures that convert 80% of the rhodopsin in the eye to metarhodopsin, rhabdoms become covered with accessory pigment and appear to lose some microvillar order. Only after a delay of hours or even days is the metarhodopsin replaced by rhodopsin (Cronin and Goldsmith 1984). After 24 h of dark adaptation, when there has been little recovery of visual pigment, the photoreceptor cells have normal resting potentials and input resistances, and the reversal potential of the light response is 10-15 mV (inside positive), unchanged from controls. The log V vs log I curve is shifted about 0.6 log units to the right on the energy axis, quantitatively consistent with the decrease in the probability of quantum catch expected from the lowered concentration of rhodopsin in the rhabdoms. Furthermore, at 24 h the photoreceptors exhibit a broader spectral sensitivity than controls, which is also expected from accumulations of metarhodopsin in the rhabdoms. In three other respects, however, the transduction process appears to be light adapted: The voltage responses are more phasic than those of control photoreceptors. The relatively larger effect (compared to controls) of low extracellular Ca++ (1 mmol/l EGTA) in potentiating the photoresponses suggests that the photoreceptors may have elevated levels of free cytoplasmic Ca++. The saturating depolarization is only about 30% as large as the maximal receptor potentials of contralateral, dark controls, and by that measure the log V-log I curve is shifted downward by 0.54 log units.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Computer modeling describes gravity-related adaptation in cell cultures.

    Science.gov (United States)

    Alexandrov, Ludmil B; Alexandrova, Stoyana; Usheva, Anny

    2009-12-16

    Questions about the changes of biological systems in response to hostile environmental factors are important but not easy to answer. Often, the traditional description with differential equations is difficult due to the overwhelming complexity of the living systems. Another way to describe complex systems is by simulating them with phenomenological models such as the well-known evolutionary agent-based model (EABM). Here we developed an EABM to simulate cell colonies as a multi-agent system that adapts to hyper-gravity in starvation conditions. In the model, the cell's heritable characteristics are generated and transferred randomly to offspring cells. After a qualitative validation of the model at normal gravity, we simulate cellular growth in hyper-gravity conditions. The obtained data are consistent with previously confirmed theoretical and experimental findings for bacterial behavior in environmental changes, including the experimental data from the microgravity Atlantis and the Hypergravity 3000 experiments. Our results demonstrate that it is possible to utilize an EABM with realistic qualitative description to examine the effects of hypergravity and starvation on complex cellular entities.

  12. Interactions between Innate Lymphoid Cells and Cells of the Innate and Adaptive Immune System.

    Science.gov (United States)

    Symowski, Cornelia; Voehringer, David

    2017-01-01

    Type 2 innate lymphoid cells (ILC2s) are a major source of cytokines, which are also produced by Th2 cells and several cell types of the innate immune system. Work over the past few years indicates that ILC2s play a central role in regulating type 2 immune responses against allergens and helminths. ILC2s can interact with a variety of cells types of the innate and adaptive immune system by cell-cell contacts or by communication via soluble factors. In this review, we provide an overview about recent advances in our understanding how ILC2s orchestrate type 2 immune responses with focus on direct interactions between ILC2s and other cells of the immune system.

  13. Haunted Bodies: Cell Switching, Getting Lost and Adaptive Geographies

    Directory of Open Access Journals (Sweden)

    Jane Grant

    2017-11-01

    Full Text Available This article proposes the ideas of stochastic resonance and noise as devices with which to think of the body or self as plural and porous. Boundaries and surfaces are proposed as indefinite; cell switching and narratives of the self are discussed in relation to external forces, via Arendt’s inter-subjectivity and La Celca’s colonization as infection. The sonic artwork Ghost, which uses models of spiking neurons to materialize endogenous and exogenous composition in relation to noise and sonic memory is presented as an exploration of the boundary or limit of the notion of self. This paper, which serves as a cogitatum (a force rather than cognitio (the result, articulates the human body as a complex and open system that steers towards chaos by adapting and accepting further complexity as, and within, constantly adaptive networks of creativity. We suggest that by focusing on the porosity of boundaries and the mechanisms that underlie their permeability, problems around identity and subjectivity might be seen in a new light.

  14. Using virtual reality to augment perception, enhance sensorimotor adaptation, and change our minds.

    Science.gov (United States)

    Wright, W Geoffrey

    2014-01-01

    Technological advances that involve human sensorimotor processes can have both intended and unintended effects on the central nervous system (CNS). This mini review focuses on the use of virtual environments (VE) to augment brain functions by enhancing perception, eliciting automatic motor behavior, and inducing sensorimotor adaptation. VE technology is becoming increasingly prevalent in medical rehabilitation, training simulators, gaming, and entertainment. Although these VE applications have often been shown to optimize outcomes, whether it be to speed recovery, reduce training time, or enhance immersion and enjoyment, there are inherent drawbacks to environments that can potentially change sensorimotor calibration. Across numerous VE studies over the years, we have investigated the effects of combining visual and physical motion on perception, motor control, and adaptation. Recent results from our research involving exposure to dynamic passive motion within a visually-depicted VE reveal that short-term exposure to augmented sensorimotor discordance can result in systematic aftereffects that last beyond the exposure period. Whether these adaptations are advantageous or not, remains to be seen. Benefits as well as risks of using VE-driven sensorimotor stimulation to enhance brain processes will be discussed.

  15. Using virtual reality to augment perception, enhance sensorimotor adaptation, and change our minds

    Directory of Open Access Journals (Sweden)

    W. Geoffrey Wright

    2014-04-01

    Full Text Available Technological advances that involve human sensorimotor processes can have both intended and unintended effects on the central nervous system (CNS. This mini-review focuses on the use of virtual environments (VE to augment brain functions by enhancing perception, eliciting automatic motor behavior, and inducing sensorimotor adaptation. VE technology is becoming increasingly prevalent in medical rehabilitation, training simulators, gaming, and entertainment. Although these VE applications have often been shown to optimize outcomes, whether it be to speed recovery, reduce training time, or enhance immersion and enjoyment, there are inherent drawbacks to environments that can potentially change sensorimotor calibration. Across numerous VE studies over the years, we have investigated the effects of combining visual and physical motion on perception, motor control, and adaptation. Recent results from our research involving exposure to dynamic passive motion within a visually-depicted VE reveal that short-term exposure to augmented sensorimotor discordance can result in systematic aftereffects that last beyond the exposure period. Whether these adaptations are advantageous or not, remains to be seen. Benefits as well as risks of using VE-driven sensorimotor stimulation to enhance brain processes will be discussed.

  16. Radioadaptive response. Efficient repair of radiation-induced DNA damage in adapted cells

    International Nuclear Information System (INIS)

    Ikushima, Takaji; Aritomi, Hisako; Morisita, Jun

    1996-01-01

    To verify the hypothesis that the induction of a novel, efficient repair mechanism for chromosomal DNA breaks may be involved in the radioadaptive response, the repair kinetics of DNA damage has been studied in cultured Chinese hamster V79 cells with single-cell gel electrophoresis. The cells were adapted by priming exposure with 5 cGy of γ-rays and 4-h incubation at 37C. There were no indication of any difference in the initial yields of DNA double-strand breaks induced by challenging doses from non-adapted cells and from adapted cells. The rejoining of DNA double-strand breaks was monitored over 120 min after the adapted cells were challenged with 5 or 1.5 Gy, doses at the same level to those used in the cytogenetical adaptive response. The rate of DNA damage repair in adapted cells was higher than that in non-adapted cells, and the residual damage was less in adapted cells than in non-adapted cells. These results indicate that the radioadaptive response may result from the induction of a novel, efficient DNA repair mechanism which leads to less residual damage, but not from the induction of protective functions that reduce the initial DNA damage

  17. Enhancing Adaptive Capacity in Food Systems: Learning at Farmers' Markets in Sweden

    Directory of Open Access Journals (Sweden)

    Rebecka Milestad

    2010-09-01

    Full Text Available This article examines how local food systems in the form of farmers' markets can enhance adaptive capacity and build social-ecological resilience. It does this by exploring the learning potential among farmers and customers. Learning can enable actors to adapt successfully and thus build adaptive capacity. Three forms of learning are investigated: instrumental, communicative, and emancipatory. These forms of learning constitute the foundation for lasting changes of behaviors. Local food systems are characterized by close links and opportunities for face-to-face interactions between consumers and producers of food, and are also institutions where farmers and customers can express and act upon their ethical values concerning food. However, local food systems are still a marginal phenomenon and cannot be accessed by all consumers. Interviews were held with customers and farmers, and the interactions between farmers and customers were observed at two farmers' markets in Sweden. Customers and farmers were found to learn and adapt to each other due to the opportunities offered by the farmers' markets. We found that farmers and customers learned in the instrumental and communicative domains, but could not confirm emancipatory learning. We concluded that the feedback between customers and farmers offers the potential for learning, which in turn contributes to adaptive capacity. This can be a driving force for building resilience in the food system.

  18. Coupling internal cerebellar models enhances online adaptation and supports offline consolidation in sensorimotor tasks.

    Science.gov (United States)

    Passot, Jean-Baptiste; Luque, Niceto R; Arleo, Angelo

    2013-01-01

    The cerebellum is thought to mediate sensorimotor adaptation through the acquisition of internal models of the body-environment interaction. These representations can be of two types, identified as forward and inverse models. The first predicts the sensory consequences of actions, while the second provides the correct commands to achieve desired state transitions. In this paper, we propose a composite architecture consisting of multiple cerebellar internal models to account for the adaptation performance of humans during sensorimotor learning. The proposed model takes inspiration from the cerebellar microcomplex circuit, and employs spiking neurons to process information. We investigate the intrinsic properties of the cerebellar circuitry subserving efficient adaptation properties, and we assess the complementary contributions of internal representations by simulating our model in a procedural adaptation task. Our simulation results suggest that the coupling of internal models enhances learning performance significantly (compared with independent forward and inverse models), and it allows for the reproduction of human adaptation capabilities. Furthermore, we provide a computational explanation for the performance improvement observed after one night of sleep in a wide range of sensorimotor tasks. We predict that internal model coupling is a necessary condition for the offline consolidation of procedural memories.

  19. Coupling internal cerebellar models enhances online adaptation and supports offline consolidation in sensorimotor tasks

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste ePassot

    2013-07-01

    Full Text Available The cerebellum is thought to mediate sensorimotor adaptation through the acquisition of internal models of the body–environment interaction. These representations can be of two types, identified as forward and inverse models. The first predicts the sensory consequences of actions, while the second provides the correct commands to achieve desired state transitions. In this paper, we propose a composite architecture consisting of multiple cerebellar internal models to account for the adaptation performance of humans during sensorimotor learning. The proposed model takes inspiration from the cerebellar microcomplex circuit, and employs spiking neurons to process information. We investigate the intrinsic properties of the cerebellar circuitry subserving efficient adaptation properties, and we assess the complementary contributions of internal representations by simulating our model in a procedural adaptation task. Our simulation results suggest that the coupling of internal models enhances learning performance significantly (compared with independent forward and inverse models, and it allows for the reproduction of human adaptation capabilities. Furthermore, we provide a computational explanation for the performance improvement observed after one night of sleep in a wide range of sensorimotor tasks. We predict that internal model coupling is a necessary condition for the offline consolidation of procedural memories.

  20. Dissecting engineered cell types and enhancing cell fate conversion via CellNet

    Science.gov (United States)

    Morris, Samantha A.; Cahan, Patrick; Li, Hu; Zhao, Anna M.; San Roman, Adrianna K.; Shivdasani, Ramesh A.; Collins, James J.; Daley, George Q.

    2014-01-01

    SUMMARY Engineering clinically relevant cells in vitro holds promise for regenerative medicine, but most protocols fail to faithfully recapitulate target cell properties. To address this, we developed CellNet, a network biology platform that determines whether engineered cells are equivalent to their target tissues, diagnoses aberrant gene regulatory networks, and prioritizes candidate transcriptional regulators to enhance engineered conversions. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed long-term functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells. PMID:25126792

  1. A population dynamics analysis of the interaction between adaptive regulatory T cells and antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    David Fouchet

    Full Text Available BACKGROUND: Regulatory T cells are central actors in the maintenance of tolerance of self-antigens or allergens and in the regulation of the intensity of the immune response during infections by pathogens. An understanding of the network of the interaction between regulatory T cells, antigen presenting cells and effector T cells is starting to emerge. Dynamical systems analysis can help to understand the dynamical properties of an interaction network and can shed light on the different tasks that can be accomplished by a network. METHODOLOGY AND PRINCIPAL FINDINGS: We used a mathematical model to describe a interaction network of adaptive regulatory T cells, in which mature precursor T cells may differentiate into either adaptive regulatory T cells or effector T cells, depending on the activation state of the cell by which the antigen was presented. Using an equilibrium analysis of the mathematical model we show that, for some parameters, the network has two stable equilibrium states: one in which effector T cells are strongly regulated by regulatory T cells and another in which effector T cells are not regulated because the regulatory T cell population is vanishingly small. We then simulate different types of perturbations, such as the introduction of an antigen into a virgin system, and look at the state into which the system falls. We find that whether or not the interaction network switches from the regulated (tolerant state to the unregulated state depends on the strength of the antigenic stimulus and the state from which the network has been perturbed. CONCLUSION/SIGNIFICANCE: Our findings suggest that the interaction network studied in this paper plays an essential part in generating and maintaining tolerance against allergens and self-antigens.

  2. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation.

    Science.gov (United States)

    Calafate, Sara; Buist, Arjan; Miskiewicz, Katarzyna; Vijayan, Vinoy; Daneels, Guy; de Strooper, Bart; de Wit, Joris; Verstreken, Patrik; Moechars, Diederik

    2015-05-26

    Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer's disease (AD). Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Selection of metastatic breast cancer cells based on adaptability of their metabolic state.

    Directory of Open Access Journals (Sweden)

    Balraj Singh

    Full Text Available A small subpopulation of highly adaptable breast cancer cells within a vastly heterogeneous population drives cancer metastasis. Here we describe a function-based strategy for selecting rare cancer cells that are highly adaptable and drive malignancy. Although cancer cells are dependent on certain nutrients, e.g., glucose and glutamine, we hypothesized that the adaptable cancer cells that drive malignancy must possess an adaptable metabolic state and that such cells could be identified using a robust selection strategy. As expected, more than 99.99% of cells died upon glutamine withdrawal from the aggressive breast cancer cell line SUM149. The rare cells that survived and proliferated without glutamine were highly adaptable, as judged by additional robust adaptability assays involving prolonged cell culture without glucose or serum. We were successful in isolating rare metabolically plastic glutamine-independent (Gln-ind variants from several aggressive breast cancer cell lines that we tested. The Gln-ind cells overexpressed cyclooxygenase-2, an indicator of tumor aggressiveness, and they were able to adjust their glutaminase level to suit glutamine availability. The Gln-ind cells were anchorage-independent, resistant to chemotherapeutic drugs doxorubicin and paclitaxel, and resistant to a high concentration of a COX-2 inhibitor celecoxib. The number of cells being able to adapt to non-availability of glutamine increased upon prior selection of cells for resistance to chemotherapy drugs or resistance to celecoxib, further supporting a linkage between cellular adaptability and therapeutic resistance. Gln-ind cells showed indications of oxidative stress, and they produced cadherin11 and vimentin, indicators of mesenchymal phenotype. Gln-ind cells were more tumorigenic and more metastatic in nude mice than the parental cell line as judged by incidence and time of occurrence. As we decreased the number of cancer cells in xenografts, lung metastasis

  4. Selection of Metastatic Breast Cancer Cells Based on Adaptability of Their Metabolic State

    Science.gov (United States)

    Singh, Balraj; Tai, Karen; Madan, Simran; Raythatha, Milan R.; Cady, Amanda M.; Braunlin, Megan; Irving, LaTashia R.; Bajaj, Ankur; Lucci, Anthony

    2012-01-01

    A small subpopulation of highly adaptable breast cancer cells within a vastly heterogeneous population drives cancer metastasis. Here we describe a function-based strategy for selecting rare cancer cells that are highly adaptable and drive malignancy. Although cancer cells are dependent on certain nutrients, e.g., glucose and glutamine, we hypothesized that the adaptable cancer cells that drive malignancy must possess an adaptable metabolic state and that such cells could be identified using a robust selection strategy. As expected, more than 99.99% of cells died upon glutamine withdrawal from the aggressive breast cancer cell line SUM149. The rare cells that survived and proliferated without glutamine were highly adaptable, as judged by additional robust adaptability assays involving prolonged cell culture without glucose or serum. We were successful in isolating rare metabolically plastic glutamine-independent (Gln-ind) variants from several aggressive breast cancer cell lines that we tested. The Gln-ind cells overexpressed cyclooxygenase-2, an indicator of tumor aggressiveness, and they were able to adjust their glutaminase level to suit glutamine availability. The Gln-ind cells were anchorage-independent, resistant to chemotherapeutic drugs doxorubicin and paclitaxel, and resistant to a high concentration of a COX-2 inhibitor celecoxib. The number of cells being able to adapt to non-availability of glutamine increased upon prior selection of cells for resistance to chemotherapy drugs or resistance to celecoxib, further supporting a linkage between cellular adaptability and therapeutic resistance. Gln-ind cells showed indications of oxidative stress, and they produced cadherin11 and vimentin, indicators of mesenchymal phenotype. Gln-ind cells were more tumorigenic and more metastatic in nude mice than the parental cell line as judged by incidence and time of occurrence. As we decreased the number of cancer cells in xenografts, lung metastasis and then primary

  5. Enhanced phytate dephosphorylation by using Candida melibiosica yeast-based biofuel cell.

    Science.gov (United States)

    Hubenova, Yolina; Georgiev, Danail; Mitov, Mario

    2014-10-01

    We report for the first time that Candida melibiosica expresses enhanced phytase activity when grown under biofuel cell polarization in a nutrient-poor medium, containing only fructose as a carbohydrate source. Phytase activity during the cultivation under polarization reached up to 25 U per g dry biomass, exceeding with 20 ± 3 % those of the control. A participation of the enzyme in the adaptation processes to the stress conditions is proposed. In addition, steady-state electrical outputs were achieved during biofuel cell operation at continuous polarization under constant load. The obtained results show that C. melibiosica yeast-based biofuel cell could be used for simultaneous electricity generation and phytate bioremediation.

  6. Training Enhances Both Locomotor and Cognitive Adaptability to a Novel Sensory Environment

    Science.gov (United States)

    Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Brady, R. A.; Batson, C. D.; Ploutz-Snyder, R. J.; Cohen, H. S.

    2010-01-01

    During adaptation to novel gravitational environments, sensorimotor disturbances have the potential to disrupt the ability of astronauts to perform required mission tasks. The goal of this project is to develop a sensorimotor adaptability (SA) training program to facilitate rapid adaptation. We have developed a unique training system comprised of a treadmill placed on a motion-base facing a virtual visual scene that provides an unstable walking surface combined with incongruent visual flow designed to enhance sensorimotor adaptability. The goal of our present study was to determine if SA training improved both the locomotor and cognitive responses to a novel sensory environment and to quantify the extent to which training would be retained. Methods: Twenty subjects (10 training, 10 control) completed three, 30-minute training sessions during which they walked on the treadmill while receiving discordant support surface and visual input. Control subjects walked on the treadmill but did not receive any support surface or visual alterations. To determine the efficacy of training all subjects performed the Transfer Test upon completion of training. For this test, subjects were exposed to novel visual flow and support surface movement, not previously experienced during training. The Transfer Test was performed 20 minutes, 1 week, 1, 3 and 6 months after the final training session. Stride frequency, auditory reaction time, and heart rate data were collected as measures of postural stability, cognitive effort and anxiety, respectively. Results: Using mixed effects regression methods we determined that subjects who received SA training showed less alterations in stride frequency, auditory reaction time and heart rate compared to controls. Conclusion: Subjects who received SA training improved performance across a number of modalities including enhanced locomotor function, increased multi-tasking capability and reduced anxiety during adaptation to novel discordant sensory

  7. Managing inter-cell interference with advanced receivers and rank adaptation in 5G small cells

    DEFF Research Database (Denmark)

    Tavares, Fernando Menezes Leitão; Berardinelli, Gilberto; Catania, Davide

    2015-01-01

    -cell interference management. In this paper, we evaluate whether it is possible to rely on such advanced receivers as the main tool to deal with the inter-cell interference problem. We present a system-level performance evaluation in three different dense indoor small cell scenarios using a receiver model...... that includes both interference rejection combining (IRC) and successive interference cancellation (SIC) principles, as well as different rank adaptation strategies. Our results confirm that interference suppression receivers with a supportive system design can indeed represent a valid alternative to frequency...

  8. Interplay between cytoskeletal stresses and cell adaptation under chronic flow.

    Directory of Open Access Journals (Sweden)

    Deepika Verma

    Full Text Available Using stress sensitive FRET sensors we have measured cytoskeletal stresses in α-actinin and the associated reorganization of the actin cytoskeleton in cells subjected to chronic shear stress. We show that long-term shear stress reduces the average actinin stress and this effect is reversible with removal of flow. The flow-induced changes in cytoskeletal stresses are found to be dynamic, involving a transient decrease in stress (phase-I, a short-term increase (3-6 min (Phase-II, followed by a longer-term decrease that reaches a minimum in ~20 min (Phase-III, before saturating. These changes are accompanied by reorganization of the actin cytoskeleton from parallel F-actin bundles to peripheral bundles. Blocking mechanosensitive ion channels (MSCs with Gd(3+ and GsMTx4 (a specific inhibitor eliminated the changes in cytoskeletal stress and the corresponding actin reorganization, indicating that Ca(2+ permeable MSCs participate in the signaling cascades. This study shows that shear stress induced cell adaptation is mediated via MSCs.

  9. Adaptation

    International Development Research Centre (IDRC) Digital Library (Canada)

    building skills, knowledge or networks on adaptation, ... the African partners leading the AfricaAdapt network, together with the UK-based Institute of Development Studies; and ... UNCCD Secretariat, Regional Coordination Unit for Africa, Tunis, Tunisia .... 26 Rural–urban Cooperation on Water Management in the Context of.

  10. SHORT-TERM STRESS ENHANCES CELLULAR IMMUNITY AND INCREASES EARLY RESISTANCE TO SQUAMOUS CELL CARCINOMA

    OpenAIRE

    Dhabhar, Firdaus S.; Saul, Alison N.; Daugherty, Christine; Holmes, Tyson H.; Bouley, Donna M.; Oberyszyn, Tatiana M.

    2009-01-01

    In contrast to chronic/long-term stress that suppresses/dysregulates immune function, an acute/short-term fight-or-flight stress response experienced during immune activation can enhance innate and adaptive immunity. Moderate ultraviolet-B (UV) exposure provides a non-invasive system for studying the naturalistic emergence, progression and regression of squamous cell carcinoma (SCC). Because SCC is an immunoresponsive cancer, we hypothesized that short-term stress experienced before UV exposu...

  11. Enhancement of increments in spectral amplitude: further evidence for a mechanism based on central adaptation.

    Science.gov (United States)

    Carcagno, Samuele; Semal, Catherine; Demany, Laurent

    2013-01-01

    The threshold for detecting a tone in a multitone masker is lower when the masker-plus-signal stimulus is preceded by a copy of the masker. One potential explanation of this "enhancement" phenomenon is that the -precursor stimulus acts as a "template" of the subsequent masker, thus helping listeners to segregate the signal from the masker. To assess this idea, we measured enhancement for precursors that were perceptually similar to the masker and for precursors that were made dissimilar to the masker by gating their components asynchronously. We found that the two types of precursor produced similar amounts of enhancement. This was true not only when the precursor and the subsequent test stimulus were presented to the same ear but also when they were presented to opposite ears. In a second experiment, we checked that the precursors with asynchronously gated components were perceptually poor templates of the subsequent maskers. Listeners now had to discriminate between test stimuli -containing the same components as the precursor and test stimuli containing all but one of the precursor components. We found that in this experimental situation, where enhancement could play no role, gating the precursor components asynchronously disrupted performance. Overall, our results are inconsistent with the hypothesis that precursors producing enhancement are beneficial because they are used as perceptual templates of the masker. Our results are instead consistent with an -explanation of enhancement based on selective neural adaptation taking place at a central locus of the auditory system.

  12. Insulin receptor substrate 1 expression enhances the sensitivity of 32D cells to chemotherapy-induced cell death

    International Nuclear Information System (INIS)

    Porter, Holly A.; Carey, Gregory B.; Keegan, Achsah D.

    2012-01-01

    The adapters IRS1 and IRS2 link growth factor receptors to downstream signaling pathways that regulate proliferation and survival. Both suppress factor-withdrawal-induced apoptosis and have been implicated in cancer progression. However, recent studies suggest IRS1 and IRS2 mediate differential functions in cancer pathogenesis. IRS1 promoted breast cancer proliferation, while IRS2 promoted metastasis. The role of IRS1 and IRS2 in controlling cell responses to chemotherapy is unknown. To determine the role of IRS1 and IRS2 in the sensitivity of cells to chemotherapy, we treated 32D cells lacking or expressing IRS proteins with various concentrations of chemotherapeutic agents. We found that expression of IRS1, in contrast to IRS2, enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. When IRS2 was expressed with IRS1, the cells no longer showed enhanced sensitivity. Expression of IRS1 did not alter the expression of pro- and anti-apoptotic proteins; however, 32D-IRS1 cells expressed higher levels of Annexin A2. In 32D-IRS1 cells, IRS1 and Annexin A2 were both located in cytoplasmic and membrane fractions. We also found that IRS1 coprecipitated with Annexin A2, while IRS2 did not. Decreasing Annexin A2 levels reduced 32D-IRS1 cell sensitivity to chemotherapy. These results suggest IRS1 enhances sensitivity to chemotherapy in part through Annexin A2. -- Highlights: ► IRS1 enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. ► This sensitivity is abrogated by the expression of IRS2. ► Expressing IRS1 in 32D cells increased levels of Annexin A2. ► Both IRS1 and Annexin A2 were located in cytoplasmic and membrane fractions. ► Decreasing Annexin A2 in 32D-IRS1 cells abated their sensitivity to chemotherapy.

  13. Inhibition of glutathione synthesis eliminates the adaptive response of ascitic hepatoma 22 cells to nedaplatin that targets thioredoxin reductase

    International Nuclear Information System (INIS)

    Wang, Yijun; Lu, Hongjuan; Wang, Dongxu; Li, Shengrong; Sun, Kang; Wan, Xiaochun; Taylor, Ethan Will; Zhang, Jinsong

    2012-01-01

    Thioredoxin reductase (TrxR) is a target for cancer therapy and the anticancer mechanism of cisplatin involves TrxR inhibition. We hypothesize that the anticancer drug nedaplatin (NDP), an analogue of cisplatin and a second-generation platinum complex, also targets TrxR. Furthermore, we investigate whether the therapeutic efficacy of NDP can be enhanced by simultaneous modulation of 1) TrxR, via NDP, and 2) glutathione (GSH), via the GSH synthesis inhibitor buthionine sulfoximine (BSO). Mice bearing ascitic hepatoma 22 (H22) cells were treated with NDP alone or NDP plus BSO. TrxR activity of H22 cells was inhibited by NDP in a dose-dependent manner. A high correlation between the inhibition of TrxR activity at 6 h and the inhibition of ascitic fluid volume at 72 h was established (r = 0.978, p < 0.01). As an adaptive response, the viable ascitic cancer cells after NDP treatment displayed an enlarged cell phenotype, assembled with several-fold more antioxidant enzymes and GSH-predominant non-protein free thiols. This adaptive response was largely eliminated when BSO was co-administered with NDP, leading to the decimation of the H22 cell population without enhancing renal toxicity, since at this dose, NDP did not inhibit renal TrxR activity. In conclusion, the pharmacological effect of NDP involves TrxR inhibition, and the adaptive response of NDP-treated ascitic H22 cells can be efficiently counteracted by BSO. Simultaneous modulation of TrxR and GSH on ascitic H22 cells using NDP plus BSO greatly enhances therapeutic efficacy as compared with the single modulation of TrxR using NDP alone. -- Highlights: ► Nedaplatin at a pharmacological dose inhibits TrxR in cancer cells but not in kidney. ► The nedaplatin-treated cancer cells exhibit adaptive response. ► Buthionine sulfoximine inhibits glutathione in both cancer cells and kidney. ► Buthionine sulfoximine counteracts the adaptive response to the nedaplatin treatment. ► Buthionine sulfoximine does not

  14. Inhibition of glutathione synthesis eliminates the adaptive response of ascitic hepatoma 22 cells to nedaplatin that targets thioredoxin reductase

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yijun [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Lu, Hongjuan [Productivity Center of Jiangsu Province, Nanjing 210042, Jiangsu (China); Wang, Dongxu; Li, Shengrong; Sun, Kang; Wan, Xiaochun [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Taylor, Ethan Will [Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, University of North Carolina at Greensboro, Greensboro, NC 27402 (United States); Zhang, Jinsong, E-mail: zjs@ahau.edu.cn [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China)

    2012-12-15

    Thioredoxin reductase (TrxR) is a target for cancer therapy and the anticancer mechanism of cisplatin involves TrxR inhibition. We hypothesize that the anticancer drug nedaplatin (NDP), an analogue of cisplatin and a second-generation platinum complex, also targets TrxR. Furthermore, we investigate whether the therapeutic efficacy of NDP can be enhanced by simultaneous modulation of 1) TrxR, via NDP, and 2) glutathione (GSH), via the GSH synthesis inhibitor buthionine sulfoximine (BSO). Mice bearing ascitic hepatoma 22 (H22) cells were treated with NDP alone or NDP plus BSO. TrxR activity of H22 cells was inhibited by NDP in a dose-dependent manner. A high correlation between the inhibition of TrxR activity at 6 h and the inhibition of ascitic fluid volume at 72 h was established (r = 0.978, p < 0.01). As an adaptive response, the viable ascitic cancer cells after NDP treatment displayed an enlarged cell phenotype, assembled with several-fold more antioxidant enzymes and GSH-predominant non-protein free thiols. This adaptive response was largely eliminated when BSO was co-administered with NDP, leading to the decimation of the H22 cell population without enhancing renal toxicity, since at this dose, NDP did not inhibit renal TrxR activity. In conclusion, the pharmacological effect of NDP involves TrxR inhibition, and the adaptive response of NDP-treated ascitic H22 cells can be efficiently counteracted by BSO. Simultaneous modulation of TrxR and GSH on ascitic H22 cells using NDP plus BSO greatly enhances therapeutic efficacy as compared with the single modulation of TrxR using NDP alone. -- Highlights: ► Nedaplatin at a pharmacological dose inhibits TrxR in cancer cells but not in kidney. ► The nedaplatin-treated cancer cells exhibit adaptive response. ► Buthionine sulfoximine inhibits glutathione in both cancer cells and kidney. ► Buthionine sulfoximine counteracts the adaptive response to the nedaplatin treatment. ► Buthionine sulfoximine does not

  15. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

  16. Performance Enhancement of Pharmacokinetic Diffuse Fluorescence Tomography by Use of Adaptive Extended Kalman Filtering.

    Science.gov (United States)

    Wang, Xin; Wu, Linhui; Yi, Xi; Zhang, Yanqi; Zhang, Limin; Zhao, Huijuan; Gao, Feng

    2015-01-01

    Due to both the physiological and morphological differences in the vascularization between healthy and diseased tissues, pharmacokinetic diffuse fluorescence tomography (DFT) can provide contrast-enhanced and comprehensive information for tumor diagnosis and staging. In this regime, the extended Kalman filtering (EKF) based method shows numerous advantages including accurate modeling, online estimation of multiparameters, and universal applicability to any optical fluorophore. Nevertheless the performance of the conventional EKF highly hinges on the exact and inaccessible prior knowledge about the initial values. To address the above issues, an adaptive-EKF scheme is proposed based on a two-compartmental model for the enhancement, which utilizes a variable forgetting-factor to compensate the inaccuracy of the initial states and emphasize the effect of the current data. It is demonstrated using two-dimensional simulative investigations on a circular domain that the proposed adaptive-EKF can obtain preferable estimation of the pharmacokinetic-rates to the conventional-EKF and the enhanced-EKF in terms of quantitativeness, noise robustness, and initialization independence. Further three-dimensional numerical experiments on a digital mouse model validate the efficacy of the method as applied in realistic biological systems.

  17. Algorithm Design and Validation for Adaptive Nonlinear Control Enhancement (ADVANCE) Technology Development for Resilient Flight Control, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — SSCI proposes to develop and test a framework referred to as the ADVANCE (Algorithm Design and Validation for Adaptive Nonlinear Control Enhancement), within which...

  18. UV-enhanced reactivation in mammalian cells: increase by caffeine

    International Nuclear Information System (INIS)

    Lytle, C.D.; Iacangelo, A.L.; Lin, C.H.; Goddard, J.G.

    1981-01-01

    It has been reported that caffeine decreases UV-enhanced reactivation of UV-irradiated Herpes simplex virus in CV-l monkey kidney cells. That occurred when there was no delay between cell irradiation and virus infection. In the present study, virus infection was delayed following cell irradiation to allow an 'induction' period separate from the 'expression' period which occurs during the virus infection. Thus, the effects of caffeine on 'induction' and 'expression' could be determined separately. Caffeine increased the expression of UV-enhanced reactivation, while causing a small decrease in the 'induction' of enhanced reactivation. (author)

  19. A biological inspired fuzzy adaptive window median filter (FAWMF) for enhancing DNA signal processing.

    Science.gov (United States)

    Ahmad, Muneer; Jung, Low Tan; Bhuiyan, Al-Amin

    2017-10-01

    Digital signal processing techniques commonly employ fixed length window filters to process the signal contents. DNA signals differ in characteristics from common digital signals since they carry nucleotides as contents. The nucleotides own genetic code context and fuzzy behaviors due to their special structure and order in DNA strand. Employing conventional fixed length window filters for DNA signal processing produce spectral leakage and hence results in signal noise. A biological context aware adaptive window filter is required to process the DNA signals. This paper introduces a biological inspired fuzzy adaptive window median filter (FAWMF) which computes the fuzzy membership strength of nucleotides in each slide of window and filters nucleotides based on median filtering with a combination of s-shaped and z-shaped filters. Since coding regions cause 3-base periodicity by an unbalanced nucleotides' distribution producing a relatively high bias for nucleotides' usage, such fundamental characteristic of nucleotides has been exploited in FAWMF to suppress the signal noise. Along with adaptive response of FAWMF, a strong correlation between median nucleotides and the Π shaped filter was observed which produced enhanced discrimination between coding and non-coding regions contrary to fixed length conventional window filters. The proposed FAWMF attains a significant enhancement in coding regions identification i.e. 40% to 125% as compared to other conventional window filters tested over more than 250 benchmarked and randomly taken DNA datasets of different organisms. This study proves that conventional fixed length window filters applied to DNA signals do not achieve significant results since the nucleotides carry genetic code context. The proposed FAWMF algorithm is adaptive and outperforms significantly to process DNA signal contents. The algorithm applied to variety of DNA datasets produced noteworthy discrimination between coding and non-coding regions contrary

  20. Enhanced endogenous type I interferon cell-driven survival and inhibition of spontaneous apoptosis by Riluzole

    International Nuclear Information System (INIS)

    Achour, Ammar; M'Bika, Jean-Pierre; Biquard, Jean-Michel

    2009-01-01

    Highly active antiretroviral therapy (HAART), although effective in improving the survival of HIV-1-infected individuals, has not been able to reconstitute the adaptive immune response. We have described the use of novel chemical agents to restore T-cell survival/proliferation by inducing cytokine production. Due to its cationic amphiphilic structure, these molecules appear to enhance immune restoration. In this study, we investigated the action of Riluzole (2-amino-6-trifuromethoxybenzothiazole) in HIV-1 infection. Riluzole is able to increase (effective dose from 1 to 1000 nM) the cell-survival of T cells from HIV-1-infected patients and inhibit spontaneous apoptosis. The immunomodulatory effect of riluzole-sensitized cells was ascribed to endogenous type I interferon (IFN) derived from monocytes. Riluzole might be used for restoring the cell survival of immunocompromised patients and eliminating latent infected cells upon HIV-1 reactivation

  1. Microgravity-Enhanced Stem Cell Selection

    Science.gov (United States)

    Claudio, Pier Paolo; Valluri, Jagan

    2011-01-01

    Stem cells, both embryonic and adult, promise to revolutionize the practice of medicine in the future. In order to realize this potential, a number of hurdles must be overcome. Most importantly, the signaling mechanisms necessary to control the differentiation of stem cells into tissues of interest remain to be elucidated, and much of the present research on stem cells is focused on this goal. Nevertheless, it will also be essential to achieve large-scale expansion and, in many cases, assemble cells in 3D as transplantable tissues. To this end, microgravity analog bioreactors can play a significant role. Microgravity bioreactors were originally conceived as a tool to study the cellular responses to microgravity. However, the technology can address some of the shortcomings of conventional cell culture systems; namely, the deficiency of mass transport in static culture and high mechanical shear forces in stirred systems. Unexpectedly, the conditions created in the vessel were ideal for 3D cell culture. Recently, investigators have demonstrated the capability of the microgravity bioreactors to expand hematopoietic stem cells compared to static culture, and facilitate the differentiation of umbilical cord stem cells into 3D liver aggregates. Stem cells are capable of differentiating into functional cells. However, there are no reliable methods to induce the stem cells to form specific cells or to gain enough cells for transplantation, which limits their application in clinical therapy. The aim of this study is to select the best experimental setup to reach high proliferation levels by culturing these cells in a microgravity-based bioreactor. In typical cell culture, the cells sediment to the bottom surface of their container and propagate as a one-cell-layer sheet. Prevention of such sedimentation affords the freedom for self-assembly and the propagation of 3D tissue arrays. Suspension of cells is easily achievable using stirred technologies. Unfortunately, in

  2. Forskolin suppresses delayed-rectifier K+ currents and enhances spike frequency-dependent adaptation of sympathetic neurons.

    Directory of Open Access Journals (Sweden)

    Luis I Angel-Chavez

    Full Text Available In signal transduction research natural or synthetic molecules are commonly used to target a great variety of signaling proteins. For instance, forskolin, a diterpene activator of adenylate cyclase, has been widely used in cellular preparations to increase the intracellular cAMP level. However, it has been shown that forskolin directly inhibits some cloned K+ channels, which in excitable cells set up the resting membrane potential, the shape of action potential and regulate repetitive firing. Despite the growing evidence indicating that K+ channels are blocked by forskolin, there are no studies yet assessing the impact of this mechanism of action on neuron excitability and firing patterns. In sympathetic neurons, we find that forskolin and its derivative 1,9-Dideoxyforskolin, reversibly suppress the delayed rectifier K+ current (IKV. Besides, forskolin reduced the spike afterhyperpolarization and enhanced the spike frequency-dependent adaptation. Given that IKV is mostly generated by Kv2.1 channels, HEK-293 cells were transfected with cDNA encoding for the Kv2.1 α subunit, to characterize the mechanism of forskolin action. Both drugs reversible suppressed the Kv2.1-mediated K+ currents. Forskolin inhibited Kv2.1 currents and IKV with an IC50 of ~32 μM and ~24 µM, respectively. Besides, the drug induced an apparent current inactivation and slowed-down current deactivation. We suggest that forskolin reduces the excitability of sympathetic neurons by enhancing the spike frequency-dependent adaptation, partially through a direct block of their native Kv2.1 channels.

  3. Forskolin suppresses delayed-rectifier K+ currents and enhances spike frequency-dependent adaptation of sympathetic neurons.

    Science.gov (United States)

    Angel-Chavez, Luis I; Acosta-Gómez, Eduardo I; Morales-Avalos, Mario; Castro, Elena; Cruzblanca, Humberto

    2015-01-01

    In signal transduction research natural or synthetic molecules are commonly used to target a great variety of signaling proteins. For instance, forskolin, a diterpene activator of adenylate cyclase, has been widely used in cellular preparations to increase the intracellular cAMP level. However, it has been shown that forskolin directly inhibits some cloned K+ channels, which in excitable cells set up the resting membrane potential, the shape of action potential and regulate repetitive firing. Despite the growing evidence indicating that K+ channels are blocked by forskolin, there are no studies yet assessing the impact of this mechanism of action on neuron excitability and firing patterns. In sympathetic neurons, we find that forskolin and its derivative 1,9-Dideoxyforskolin, reversibly suppress the delayed rectifier K+ current (IKV). Besides, forskolin reduced the spike afterhyperpolarization and enhanced the spike frequency-dependent adaptation. Given that IKV is mostly generated by Kv2.1 channels, HEK-293 cells were transfected with cDNA encoding for the Kv2.1 α subunit, to characterize the mechanism of forskolin action. Both drugs reversible suppressed the Kv2.1-mediated K+ currents. Forskolin inhibited Kv2.1 currents and IKV with an IC50 of ~32 μM and ~24 µM, respectively. Besides, the drug induced an apparent current inactivation and slowed-down current deactivation. We suggest that forskolin reduces the excitability of sympathetic neurons by enhancing the spike frequency-dependent adaptation, partially through a direct block of their native Kv2.1 channels.

  4. Photo-Oxidative Stress-Driven Mutagenesis and Adaptive Evolution on the Marine Diatom Phaeodactylum tricornutum for Enhanced Carotenoid Accumulation

    Directory of Open Access Journals (Sweden)

    Zhiqian Yi

    2015-09-01

    Full Text Available Marine diatoms have recently gained much attention as they are expected to be a promising resource for sustainable production of bioactive compounds such as carotenoids and biofuels as a future clean energy solution. To develop photosynthetic cell factories, it is important to improve diatoms for value-added products. In this study, we utilized UVC radiation to induce mutations in the marine diatom Phaeodactylum tricornutum and screened strains with enhanced accumulation of neutral lipids and carotenoids. Adaptive laboratory evolution (ALE was also used in parallel to develop altered phenotypic and biological functions in P. tricornutum and it was reported for the first time that ALE was successfully applied on diatoms for the enhancement of growth performance and productivity of value-added carotenoids to date. Liquid chromatography-mass spectrometry (LC-MS was utilized to study the composition of major pigments in the wild type P. tricornutum, UV mutants and ALE strains. UVC radiated strains exhibited higher accumulation of fucoxanthin as well as neutral lipids compared to their wild type counterpart. In addition to UV mutagenesis, P. tricornutum strains developed by ALE also yielded enhanced biomass production and fucoxanthin accumulation under combined red and blue light. In short, both UV mutagenesis and ALE appeared as an effective approach to developing desired phenotypes in the marine diatoms via electromagnetic radiation-induced oxidative stress.

  5. Ethacrynic acid: a novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Khil, Mark S.; Sang, Hie Kim; Pinto, John T.; Jae, Ho Kim

    1996-01-01

    Purpose: Because agents that interfere with thiol metabolism and glutathione S-transferase (GST) functions have been shown to enhance antitumor effects of alkylating agents in vitro and in vivo, the present study was conceived on the basis that an inhibitor of GST would enhance the radiation response of some selected human carcinoma cells. Ethacrynic acid (EA) was chosen for the study because it is an effective inhibitor of GST and is a well known diuretic in humans. Methods and Materials: Experiments were carried out with well-established human tumor cells in culture growing in Eagle's minimum essential medium (MEM) supplemented with 10% fetal calf serum (FCS). Cell lines used were MCF-7, MCF-7 adriamycin resistant (AR) cells (breast carcinoma), HT-29 cells (colon carcinoma), DU-145 cells (prostate carcinoma), and U-373 cells (malignant glioma). Cell survival following the exposure of cells to drug alone, radiation alone, and a combined treatment was assayed by determining the colony-forming ability of single plated cells in culture to obtain dose-survival curves. The drug enhancement ratio was correlated with levels of GST. Results: The cytotoxicity of EA was most pronounced in MCF-7, U-373, and DU-145 cells compared to MCF-7 AR and HT-29 cells. The levels of GST activity were found to be lower in those EA-sensitive cells. A significant radiation enhancement was obtained with EA-sensitive cells exposed to nontoxic concentrations of the drug immediately before or after irradiation. The sensitizer enhancement ratio (SER) of MCF-7 cells was 1.55 with EA (20 μg/ml), while the SER of MCF-7 AR was less than 1.1. Based on five different human tumor cells, a clear inverse relationship was demonstrated between the magnitude of SER and GST levels of tumor cells prior to the combined treatment. Conclusion: The present results suggest that EA, which acts as both a reversible and irreversible inhibitor of GST activity, could significantly enhance the radiation response of

  6. Brain-specific enhancers for cell-based therapy

    Science.gov (United States)

    Visel, Axel; Rubenstein, John L.R.; Chen, Ying-Jiun; Pennacchio, Len A.; Vogt, Daniel; Nicholas, Cory; Kriegstein, Arnold

    2018-04-24

    Herein are described a set of novel specific human enhancers for specific forebrain cell types used to study and select for human neural progenitor cells. This approach enables the ability to generate interneurons from human ES, iPS and iN cells, making them available for human transplantation and for molecular/cellular analyzes. These approaches are also directly applicable to generating other neuronal cell types, such as cortical and striatal projection neurons, which have implications for many human diseases.

  7. Adaptive evolution of Saccharomyces cerevisiae with enhanced ethanol tolerance for Chinese rice wine fermentation.

    Science.gov (United States)

    Chen, Shuang; Xu, Yan

    2014-08-01

    High tolerance towards ethanol is a desirable property for the Saccharomyces cerevisiae strains used in the alcoholic beverage industry. To improve the ethanol tolerance of an industrial Chinese rice wine yeast, a sequential batch fermentation strategy was used to adaptively evolve a chemically mutagenized Chinese rice wine G85 strain. The high level of ethanol produced under Chinese rice wine-like fermentation conditions was used as the selective pressure. After adaptive evolution of approximately 200 generations, mutant G85X-8 was isolated and shown to have markedly increased ethanol tolerance. The evolved strain also showed higher osmotic and temperature tolerances than the parental strain. Laboratory Chinese rice wine fermentation showed that the evolved G85X-8 strain was able to catabolize sugars more completely than the parental G85 strain. A higher level of yeast cell activity was found in the fermentation mash produced by the evolved strain, but the aroma profiles were similar between the evolved and parental strains. The improved ethanol tolerance in the evolved strain might be ascribed to the altered fatty acids composition of the cell membrane and higher intracellular trehalose concentrations. These results suggest that adaptive evolution is an efficient approach for the non-recombinant modification of industrial yeast strains.

  8. Skeletal adaptation to intramedullary pressure-induced interstitial fluid flow is enhanced in mice subjected to targeted osteocyte ablation.

    Science.gov (United States)

    Kwon, Ronald Y; Meays, Diana R; Meilan, Alexander S; Jones, Jeremiah; Miramontes, Rosa; Kardos, Natalie; Yeh, Jiunn-Chern; Frangos, John A

    2012-01-01

    Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading

  9. Skeletal adaptation to intramedullary pressure-induced interstitial fluid flow is enhanced in mice subjected to targeted osteocyte ablation.

    Directory of Open Access Journals (Sweden)

    Ronald Y Kwon

    Full Text Available Interstitial fluid flow (IFF is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of

  10. Adapt

    Science.gov (United States)

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  11. Enhanced photovoltaic performance of an inclined nanowire array solar cell.

    Science.gov (United States)

    Wu, Yao; Yan, Xin; Zhang, Xia; Ren, Xiaomin

    2015-11-30

    An innovative solar cell based on inclined p-i-n nanowire array is designed and analyzed. The results show that the inclined geometry can sufficiently increase the conversion efficiency of solar cells by enhancing the absorption of light in the active region. By tuning the nanowire array density, nanowire diameter, nanowire length, as well as the proportion of intrinsic region of the inclined nanowire solar cell, a remarkable efficiency in excess of 16% can be obtained in GaAs. Similar results have been obtained in InP and Si nanowire solar cells, demonstrating the universality of the performance enhancement of inclined nanowire arrays.

  12. Enhancement of Diosgenin Production in Plantlet and Cell Cultures ...

    African Journals Online (AJOL)

    Enhancement of Diosgenin Production in Plantlet and Cell Cultures of Dioscorea zingiberensis by Palmarumycin C13 from the Endophytic fungus, Berkleasmium sp. Dzf12. Y Mou, K Zhou, D Xu, R Yu, J Li, C Yin, L Zhou ...

  13. Cell cycle regulation in human embryonic stem cells: links to adaptation to cell culture.

    Science.gov (United States)

    Barta, Tomas; Dolezalova, Dasa; Holubcova, Zuzana; Hampl, Ales

    2013-03-01

    Cell cycle represents not only a tightly orchestrated mechanism of cell replication and cell division but it also plays an important role in regulation of cell fate decision. Particularly in the context of pluripotent stem cells or multipotent progenitor cells, regulation of cell fate decision is of paramount importance. It has been shown that human embryonic stem cells (hESCs) show unique cell cycle characteristics, such as short doubling time due to abbreviated G1 phase; these properties change with the onset of differentiation. This review summarizes the current understanding of cell cycle regulation in hESCs. We discuss cell cycle properties as well as regulatory machinery governing cell cycle progression of undifferentiated hESCs. Additionally, we provide evidence that long-term culture of hESCs is accompanied by changes in cell cycle properties as well as configuration of several cell cycle regulatory molecules.

  14. Adaptive repair induced by small doses of γ radiation in repair-defective human cells

    International Nuclear Information System (INIS)

    Zasukhina, G.D.; L'vova, G.N.; Vasil'eva, I.M.; Sinel'shchikova, T.A.; Semyachkina, A.N.

    1993-01-01

    Adaptive repair induced by small doses of gamma radiation was studied in repair-defective xeroderma pigmentosum, gout, and homocystinuria cells. The adaptation of cells induced by small doses of radiation was estimated after subsequent exposure to gamma radiation, 4-nitroquinoline-1-oxide, and N-methyl-N-nitro-N-nitrosoguanidine by three methods: (1) by the reduction in DNA breaks; (2) by induction of resistant DNA synthesis; and (3) by increased reactivation of vaccinia virus. The three cell types in response to the three different mutagens revealed differences in the mechanism of cell defense in excision repair, in the adaptive response, and in Weigl reactivation

  15. Photovoltaic enhancement of Si solar cells by assembled carbon nanotubes

    Institute of Scientific and Technical Information of China (English)

    Y.F.Zhang; Y.F.Wang; N.Chen; Y.Y.Wang; Y.Z.Zhang; Z.H.Zhou; L.M.Wei

    2010-01-01

    Photovoltaic conversion was enhanced by directly assemble of a network of single-walled carbon nanotubes(SWNTs) onto the surface of n-p junction silicon solar cells. When the density of SWNTs increased from 50 to 400 tubes μm-2, an enhancement of 3.92% in energy conversion efficiency was typically obtained. The effect of the SWNTs network is proposed for trapping incident photons and assisting electronic transportation at the interface of silicon solar cells.

  16. [Optimization and Prognosis of Cell Radiosensitivity Enhancement in vitro and in vivo after Sequential Thermoradiactive Action].

    Science.gov (United States)

    Belkina, S V; Petin, V G

    2016-01-01

    Previously developed mathematical model of simultaneous action of two inactivating agents has been adapted and tested to describe the results of sequential action. The possibility of applying the mathematical model to the interpretation and prognosis of the increase in radio-sensitivity of tumor cells as well as mammalian cells after sequential action of two high temperatures or hyperthermia and ionizing radiation is analyzed. The model predicts the value of the thermal enhancement ratio depending on the duration of thermal exposure, its greatest value, and the condition under which it is achieved.

  17. Adaptive enhanced sampling with a path-variable for the simulation of protein folding and aggregation

    Science.gov (United States)

    Peter, Emanuel K.

    2017-12-01

    In this article, we present a novel adaptive enhanced sampling molecular dynamics (MD) method for the accelerated simulation of protein folding and aggregation. We introduce a path-variable L based on the un-biased momenta p and displacements dq for the definition of the bias s applied to the system and derive 3 algorithms: general adaptive bias MD, adaptive path-sampling, and a hybrid method which combines the first 2 methodologies. Through the analysis of the correlations between the bias and the un-biased gradient in the system, we find that the hybrid methodology leads to an improved force correlation and acceleration in the sampling of the phase space. We apply our method on SPC/E water, where we find a conservation of the average water structure. We then use our method to sample dialanine and the folding of TrpCage, where we find a good agreement with simulation data reported in the literature. Finally, we apply our methodologies on the initial stages of aggregation of a hexamer of Alzheimer's amyloid β fragment 25-35 (Aβ 25-35) and find that transitions within the hexameric aggregate are dominated by entropic barriers, while we speculate that especially the conformation entropy plays a major role in the formation of the fibril as a rate limiting factor.

  18. Use of an adaptable cell culture kit for performing lymphocyte and monocyte cell cultures in microgravity

    Science.gov (United States)

    Hatton, J. P.; Lewis, M. L.; Roquefeuil, S. B.; Chaput, D.; Cazenave, J. P.; Schmitt, D. A.

    1998-01-01

    -based investigations simulating the conditions expected in the flight experiment. Several parameters including cell concentration, time between cell loading and activation, and storage temperature on cell survival were examined to characterise cell response and optimise the experiments to be flown aboard the Space Shuttle. Results indicate that the objectives of the experiments could be met with delays up to 5 days between cell loading into the hardware and initial in flight experiment activation, without the need for medium exchange. Experiment hardware of this kind, which is adaptable to a wide range of cell types and can be easily interfaced to different spacecraft facilities, offers the possibility for a wide range of experimenters successfully and easily to utilise future flight opportunities.

  19. Improving Sensorimotor Adaptation Following Long Duration Space Flight by Enhancing Vestibular Information Transfer

    Science.gov (United States)

    Mulavara, A. P.; Kofman, I. S.; De Dios, Y. E; Galvan, R.; Goel, R.; Miller, C.; Peters, B.; Cohen, H. S.; Jeevarajan, J.; Reschke, M.; hide

    2014-01-01

    Crewmember adapted to the microgravity state may need to egress the vehicle within a few minutes for safety and operational reasons after gravitational transitions. The transition from one sensorimotor state to another consists of two main mechanisms: strategic and plastic-adaptive and have been demonstrated in astronauts returning after long duration space flight. Strategic modifications represent "early adaptation" - immediate and transitory changes in control that are employed to deal with short-term changes in the environment. If these modifications are prolonged then plastic-adaptive changes are evoked that modify central nervous system function, automating new behavioral responses. More importantly, this longer term adaptive recovery mechanism was significantly associated with their strategic ability to recover on the first day after return to Earth G. We are developing a method based on stochastic resonance to enhance information transfer by improving the brain's ability to detect vestibular signals (Vestibular Stochastic Resonance, VSR) especially when combined with balance training exercises such as sensorimotor adaptability (SA) training for rapid improvement in functional skill, for standing and mobility. This countermeasure to improve detection of vestibular signals is a stimulus delivery system that is wearable/portable providing low imperceptible levels of white noise based binaural bipolar electrical stimulation of the vestibular system (stochastic vestibular stimulation). To determine efficacy of vestibular stimulation on physiological and perceptual responses during otolith-canal conflicts and dynamic perturbations we have conducted a series of studies: We have shown that imperceptible binaural bipolar electrical stimulation of the vestibular system across the mastoids enhances balance performance in the mediolateral (ML) plane while standing on an unstable surface. We have followed up on the previous study showing VSR stimulation improved balance

  20. Estramustine: A novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Ryu, S.; Gabel, M.; Khil, M.S.

    1994-01-01

    Estramustine (EM), an antimicrotubule agent, binds microtubule-associated proteins, causes spindle disassembly, and arrests cells at the late G 2 /M phase of the cell cycle. Since cells in the G 2 /M phase are the most radiosensitive and some human cancer cells contain high level of EM-binding protein, experiments were carried out to determine whether radiation sensitization could be obtained in human carcinoma cells. Cells containing a high level of EM-binding protein such as prostate carcinoma (DU-145), breast carcinoma (MCF-7), and malignant glioma (U-251) were used to demonstrate radiosensitization. Cervical carcinoma (HeLa-S 3 ) and colon carcinoma (HT-29) cells which are not known to contain EM-binding protein were also employed. Cell survival was assayed by the colony forming ability of single plated cells in culture to obtain dose-survival curves. Pretreatment of DU-145, MCF-7, and U-251 cells to a nontoxic concentration (5 μM) of EM for more than one cell cycle time, substantially enhanced the radiation-induced cytotoxicity. The sensitizer enhancement ratio of these cells ranged from 1.35-1.52. The magnitude of the enhancement was dependent on the drug concentration and exposure time. The rate of cell accumulation in G 2 /M phase, as determined by flow cytometry, increased with longer treatment time in the cell lines which showed radiosensitization. Other antimicrotubule agents such as taxol and vinblastine caused minimal or no radiosensitization at nontoxic concentrations. The data provide a radiobiological basis for using EM as a novel radiation enhancer, with the property of tissue selectivity. 29 refs., 4 figs., 1 tab

  1. A new time-adaptive discrete bionic wavelet transform for enhancing speech from adverse noise environment

    Science.gov (United States)

    Palaniswamy, Sumithra; Duraisamy, Prakash; Alam, Mohammad Showkat; Yuan, Xiaohui

    2012-04-01

    Automatic speech processing systems are widely used in everyday life such as mobile communication, speech and speaker recognition, and for assisting the hearing impaired. In speech communication systems, the quality and intelligibility of speech is of utmost importance for ease and accuracy of information exchange. To obtain an intelligible speech signal and one that is more pleasant to listen, noise reduction is essential. In this paper a new Time Adaptive Discrete Bionic Wavelet Thresholding (TADBWT) scheme is proposed. The proposed technique uses Daubechies mother wavelet to achieve better enhancement of speech from additive non- stationary noises which occur in real life such as street noise and factory noise. Due to the integration of human auditory system model into the wavelet transform, bionic wavelet transform (BWT) has great potential for speech enhancement which may lead to a new path in speech processing. In the proposed technique, at first, discrete BWT is applied to noisy speech to derive TADBWT coefficients. Then the adaptive nature of the BWT is captured by introducing a time varying linear factor which updates the coefficients at each scale over time. This approach has shown better performance than the existing algorithms at lower input SNR due to modified soft level dependent thresholding on time adaptive coefficients. The objective and subjective test results confirmed the competency of the TADBWT technique. The effectiveness of the proposed technique is also evaluated for speaker recognition task under noisy environment. The recognition results show that the TADWT technique yields better performance when compared to alternate methods specifically at lower input SNR.

  2. CAR models: next-generation CAR modifications for enhanced T-cell function

    Directory of Open Access Journals (Sweden)

    Daniel Abate-Daga

    2016-01-01

    Full Text Available T cells genetically targeted with a chimeric antigen receptor (CAR to B-cell malignancies have demonstrated tremendous clinical outcomes. With the proof in principle for CAR T cells as a therapy for B-cell malignancies being established, current and future research is being focused on adapting CAR technology to other cancers, as well as enhancing its efficacy and/or safety. The modular nature of the CAR, extracellular antigen-binding domain fused to a transmembrane domain and intracellular T-cell signaling domains, allows for optimization by replacement of the various components. These modifications are creating a whole new class of therapeutic CARs. In this review, we discuss the recent major advances in CAR design and how these modifications will impact its clinical application.

  3. The enhancement of adaptation and psychological well-being among victims of flooding and landslide in Thailand.

    Science.gov (United States)

    Oba, Nongnut; Suntayakorn, Chanjar; Sangkaewsri, Roongsri; Longchupol, Chaowanee; Lohitpintu, Itsareat; Kumsri, Tongbai

    2010-03-01

    To explore the needs of potential enhancement for adaptation and to examine the effectiveness of the potential enhancement program for adaptation and psychological well-being among victims of flooding and landslide in Lublae district Uttaradit Province, Thailand. 3 step of research and development; the needs of potential enhancement for adaptation among victims of flooding and landslide were analyzed by focus group discussion, the potential enhancement program (PEP) was designed by brainstorming of three groups of stakeholder; victims, health volunteers and health personnel and the effectiveness of PEP was tested by the difference of adaptation and psychological well-being perception among victims of flooding and landslide between before and after intervention. Thumbun Maepou, Lublae district, Uttaradit Province, Thailand. The needs of potential enhancement among victims of flooding and landslide were set up warning network along the risk canal and mountain, first aid training for health volunteer, and program of psychological health promotion. The PEP composed of community flooding and landslide rehearsal training, health education and dissemination and knowledge management. Total adaptation and psychological wellbeing of samples after intervention were significantly higher than that of before intervention at 0.05 and 0.001, respectively. The restoration of adaptation and psychological well-being among victims of flooding and landslide were essential to maintained holistic health.

  4. Cytogenetic adaptive response of cultured fish cells to low doses of X-rays

    International Nuclear Information System (INIS)

    Kurihara, Yasuyuki; Etoh, Hisami; Rienkjkarn, M.

    1992-01-01

    The adaptive response was examining chromosomal aberrations and micronucleus in cultured fish cells, ULF-23 (mudminnow) and CAF-31 (gold fish). When cultured fish cells were first irradiated with small doses of X-rays, they became less sensitive to subsequent exposures to high doses. The effective adaptive dose was 4.8 cGy-9.5 cGy. Adaptive doses given cells in the G1 phase were more effective than when given in the S phase. The adaptive response was maximal at 5 hours and disappeared at 10 hours after the adaptive dose. The expression of the response was inhibited by treatment with 3-aminobenzamide, as reported for mammalian cells, and with arabinofuranoside cytosine, an inhibitor of DNA polymerase alpha. Caffeine, an inhibitor of post-replicational repair, had no effect on the response. (author)

  5. Cytogenetic adaptive response of cultured fish cells to low doses of X-rays

    Energy Technology Data Exchange (ETDEWEB)

    Kurihara, Yasuyuki; Etoh, Hisami (National Inst. of Radiological Sciences, Chiba (Japan)); Rienkjkarn, M.

    1992-12-01

    The adaptive response was examining chromosomal aberrations and micronucleus in cultured fish cells, ULF-23 (mudminnow) and CAF-31 (gold fish). When cultured fish cells were first irradiated with small doses of X-rays, they became less sensitive to subsequent exposures to high doses. The effective adaptive dose was 4.8 cGy-9.5 cGy. Adaptive doses given cells in the G1 phase were more effective than when given in the S phase. The adaptive response was maximal at 5 hours and disappeared at 10 hours after the adaptive dose. The expression of the response was inhibited by treatment with 3-aminobenzamide, as reported for mammalian cells, and with arabinofuranoside cytosine, an inhibitor of DNA polymerase alpha. Caffeine, an inhibitor of post-replicational repair, had no effect on the response. (author).

  6. Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

    International Nuclear Information System (INIS)

    Lee, Yoon Jae; Jang, Yo Han; Kim, Paul; Lee, Yun Ha; Lee, Young Jae; Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik; Seong, Baik Lin

    2016-01-01

    In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

  7. Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yoon Jae [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Jang, Yo Han [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Kim, Paul; Lee, Yun Ha; Lee, Young Jae [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Seong, Baik Lin, E-mail: blseong@yonsei.ac.kr [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of)

    2016-04-15

    In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

  8. Thermodynamics of photon-enhanced thermionic emission solar cells

    DEFF Research Database (Denmark)

    Reck, Kasper; Hansen, Ole

    2014-01-01

    Photon-enhanced thermionic emission (PETE) cells in which direct photon energy as well as thermal energy can be harvested have recently been suggested as a new candidate for high efficiency solar cells. Here, we present an analytic thermodynamical model for evaluation of the efficiency of PETE...

  9. Recent Visual Experience Shapes Visual Processing in Rats through Stimulus-Specific Adaptation and Response Enhancement.

    Science.gov (United States)

    Vinken, Kasper; Vogels, Rufin; Op de Beeck, Hans

    2017-03-20

    From an ecological point of view, it is generally suggested that the main goal of vision in rats and mice is navigation and (aerial) predator evasion [1-3]. The latter requires fast and accurate detection of a change in the visual environment. An outstanding question is whether there are mechanisms in the rodent visual system that would support and facilitate visual change detection. An experimental protocol frequently used to investigate change detection in humans is the oddball paradigm, in which a rare, unexpected stimulus is presented in a train of stimulus repetitions [4]. A popular "predictive coding" theory of cortical responses states that neural responses should decrease for expected sensory input and increase for unexpected input [5, 6]. Despite evidence for response suppression and enhancement in noninvasive scalp recordings in humans with this paradigm [7, 8], it has proven challenging to observe both phenomena in invasive action potential recordings in other animals [9-11]. During a visual oddball experiment, we recorded multi-unit spiking activity in rat primary visual cortex (V1) and latero-intermediate area (LI), which is a higher area of the rodent ventral visual stream. In rat V1, there was only evidence for response suppression related to stimulus-specific adaptation, and not for response enhancement. However, higher up in area LI, spiking activity showed clear surprise-based response enhancement in addition to stimulus-specific adaptation. These results show that neural responses along the rat ventral visual stream become increasingly sensitive to changes in the visual environment, suggesting a system specialized in the detection of unexpected events. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Morphological adaptations in breast cancer cells as a function of prolonged passaging on compliant substrates.

    Directory of Open Access Journals (Sweden)

    Sana Syed

    Full Text Available Standard tissue culture practices involve propagating cells on tissue culture polystyrene (TCP dishes, which are flat, 2-dimensional (2D and orders of magnitude stiffer than most tissues in the body. Such simplified conditions lead to phenotypical cell changes and altered cell behaviors. Hence, much research has been focused on developing novel biomaterials and culture conditions that more closely emulate in vivo cell microenvironments. In particular, biomaterial stiffness has emerged as a key property that greatly affects cell behaviors such as adhesion, morphology, proliferation and motility among others. Here we ask whether cells that have been conditioned to TCP, would still show significant dependence on substrate stiffness if they are first pre-adapted to a more physiologically relevant environment. We used two commonly utilized breast cancer cell lines, namely MDA-MB-231 and MCF-7, and examined the effect of prolonged cell culturing on polyacrylamide substrates of varying compliance. We followed changes in cell adhesion, proliferation, shape factor, spreading area and spreading rate. After pre-adaptation, we noted diminished differences in cell behaviors when comparing between soft (1 kPa and stiff (103 kPa gels as well as rigid TCP control. Prolonged culturing of cells on complaint substrates further influenced responses of pre-adapted cells when transferred back to TCP. Our results have implications for the study of stiffness-dependent cell behaviors and indicate that cell pre-adaptation to the substrate needs consideration.

  11. PHD-2 Suppression in Mesenchymal Stromal Cells Enhances Wound Healing.

    Science.gov (United States)

    Ko, Sae Hee; Nauta, Allison C; Morrison, Shane D; Hu, Michael S; Zimmermann, Andrew S; Chung, Michael T; Glotzbach, Jason P; Wong, Victor W; Walmsley, Graham G; Peter Lorenz, H; Chan, Denise A; Gurtner, Geoffrey C; Giaccia, Amato J; Longaker, Michael T

    2018-01-01

    Cell therapy with mesenchymal stromal cells is a promising strategy for tissue repair. Restoration of blood flow to ischemic tissues is a key step in wound repair, and mesenchymal stromal cells have been shown to be proangiogenic. Angiogenesis is critically regulated by the hypoxia-inducible factor (HIF) superfamily, consisting of transcription factors targeted for degradation by prolyl hydroxylase domain (PHD)-2. The aim of this study was to enhance the proangiogenic capability of mesenchymal stromal cells and to use these modified cells to promote wound healing. Mesenchymal stromal cells harvested from mouse bone marrow were transduced with short hairpin RNA (shRNA) against PHD-2; control cells were transduced with scrambled shRNA (shScramble) construct. Gene expression quantification, human umbilical vein endothelial cell tube formation assays, and wound healing assays were used to assess the effect of PHD knockdown mesenchymal stromal cells on wound healing dynamics. PHD-2 knockdown mesenchymal stromal cells overexpressed HIF-1α and multiple angiogenic factors compared to control (p cells treated with conditioned medium from PHD-2 knockdown mesenchymal stromal cells exhibited increased formation of capillary-like structures and enhanced migration compared with human umbilical vein endothelial cells treated with conditioned medium from shScramble-transduced mesenchymal stromal cells (p cells healed at a significantly accelerated rate compared with wounds treated with shScramble mesenchymal stromal cells (p cells (p cells augments their proangiogenic potential in wound healing therapy. This effect appears to be mediated by overexpression of HIF family transcription factors and up-regulation of multiple downstream angiogenic factors.

  12. Ficus Deltoidea Enhance Glucose Uptake Activity in Cultured Muscle Cells

    International Nuclear Information System (INIS)

    Zainah Adam; Shafii Khamis; Amin Ismail; Muhajir Hamid

    2015-01-01

    Ficus deltoidea or locally known as Mas cotek is one of the common medicinal plants used in Malaysia. Our previous studies showed that this plant have blood glucose lowering effect. Glucose uptake into muscle and adipocytes cells is one of the known mechanisms of blood glucose lowering effect. This study was performed to evaluate the effect of Ficus deltoidea on glucose uptake activity into muscle cells. The cells were incubated with Ficus deltoidea extracts either alone or combination with insulin. Amount of glucose uptake by L6 myotubes was determined using glucose tracer, 2-deoxy-(1- 3 H 1 )-glucose. The results showed that Ficus deltoidea extracts at particular doses enhanced basal or insulin-mediated glucose uptake into muscle cells significantly. Hot aqueous extract enhanced glucose uptake at the low concentration (10 μg/ ml) whereas methanolic extract enhanced glucose uptake at low and high concentrations. Methanolic extract also mimicked insulin activity during enhancing glucose uptake into L^ muscle cells. Glucose uptake activity of Ficus deltoidea could be attributed by the phenolic compound presence in the plant. This study had shown that Ficus deltoidea has the ability to enhance glucose uptake into muscle cells which is partly contributed the antidiabetic activity of this plant. (author)

  13. Polyethylene glycol enhances lipoplex-cell association and lipofection.

    Science.gov (United States)

    Ross, P C; Hui, S W

    1999-10-15

    The association between liposome-DNA complexes (lipoplexes) and targeted cell membranes is a limiting step of cationic liposome-mediated transfection. A novel technique was developed where lipoplex-cell membrane association is enhanced by the addition of 2-6% polyethylene glycol (PEG) to the transfection media. Lipoplex-cell association was found to increase up to 100 times in the presence of PEG. Transfection increased correspondingly in the presence of PEG. This increase was found in several cell lines. These results show that lipoplex adsorption to cell membranes is a critical step in liposome-mediated transfection. This step can be facilitated by PEG-induced particle aggregation.

  14. Enhanced infectivity of bluetongue virus in cell culture by centrifugation.

    OpenAIRE

    Sundin, D R; Mecham, J O

    1989-01-01

    The effects of centrifugation of the infection of cell culture with bluetongue virus (BTV) were investigated. Baby hamster kidney cells were infected with BTV with or without centrifugation. Viral antigen was detected by immunofluorescence at 24 h in both centrifuged and noncentrifuged cultures. However, after 24 h of infection, the production of PFU in centrifuged cell cultures was 10- to 20-fold greater than that seen in cultures not centrifuged. In addition, centrifugation enhanced the dir...

  15. An enhanced chaotic key-based RC5 block cipher adapted to image encryption

    Science.gov (United States)

    Faragallah, Osama S.

    2012-07-01

    RC5 is a block cipher that has several salient features such as adaptability to process different word lengths with a variable block size, a variable number of rounds and a variable-length secret key. However, RC5 can be broken with various attacks such as correlation attack, timing attack, known plaintext correlation attack and differential attacks, revealing weak security. We aimed to enhance the RC5 block cipher to be more secure and efficient for real-time applications while preserving its advantages. For this purpose, this article introduces a new approach based on strengthening both the confusion and diffusion operations by combining chaos and cryptographic primitive operations to produce round keys with better pseudo-random sequences. Comparative security analysis and performance evaluation of the enhanced RC5 block cipher (ERC5) with RC5, RC6 and chaotic block cipher algorithm (CBCA) are addressed. Several test images are used for inspecting the validity of the encryption and decryption algorithms. The experimental results show the superiority of the suggested enhanced RC5 (ERC5) block cipher to image encryption algorithms such as RC5, RC6 and CBCA from the security analysis and performance evaluation points of view.

  16. Estrogen enhanced cell-cell signalling in breast cancer cells exposed to targeted irradiation

    International Nuclear Information System (INIS)

    Shao, Chunlin; Folkard, Melvyn; Held, Kathryn D; Prise, Kevin M

    2008-01-01

    Radiation-induced bystander responses, where cells respond to their neighbours being irradiated are being extensively studied. Although evidence shows that bystander responses can be induced in many types of cells, it is not known whether there is a radiation-induced bystander effect in breast cancer cells, where the radiosensitivity may be dependent on the role of the cellular estrogen receptor (ER). This study investigated radiation-induced bystander responses in estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231 breast cancer cells. The influence of estrogen and anti-estrogen treatments on the bystander response was determined by individually irradiating a fraction of cells within the population with a precise number of helium-3 using a charged particle microbeam. Damage was scored as chromosomal damage measured as micronucleus formation. A bystander response measured as increased yield of micronucleated cells was triggered in both MCF-7 and MDA-MB-231 cells. The contribution of the bystander response to total cell damage in MCF-7 cells was higher than that in MDA-MB-231 cells although the radiosensitivity of MDA-MB-231 was higher than MCF-7. Treatment of cells with 17β-estradiol (E2) increased the radiosensitivity and the bystander response in MCF-7 cells, and the effect was diminished by anti-estrogen tamoxifen (TAM). E2 also increased the level of intracellular reactive oxygen species (ROS) in MCF-7 cells in the absence of radiation. In contrast, E2 and TAM had no influence on the bystander response and ROS levels in MDA-MB-231 cells. Moreover, the treatment of MCF-7 cells with antioxidants eliminated both the E2-induced ROS increase and E2-enhanced bystander response triggered by the microbeam irradiation, which indicates that ROS are involved in the E2-enhanced bystander micronuclei formation after microbeam irradiation. The observation of bystander responses in breast tumour cells may offer new potential targets for radiation

  17. Stochastic adaptation and fold-change detection: from single-cell to population behavior

    Directory of Open Access Journals (Sweden)

    Leier André

    2011-02-01

    Full Text Available Abstract Background In cell signaling terminology, adaptation refers to a system's capability of returning to its equilibrium upon a transient response. To achieve this, a network has to be both sensitive and precise. Namely, the system must display a significant output response upon stimulation, and later on return to pre-stimulation levels. If the system settles at the exact same equilibrium, adaptation is said to be 'perfect'. Examples of adaptation mechanisms include temperature regulation, calcium regulation and bacterial chemotaxis. Results We present models of the simplest adaptation architecture, a two-state protein system, in a stochastic setting. Furthermore, we consider differences between individual and collective adaptive behavior, and show how our system displays fold-change detection properties. Our analysis and simulations highlight why adaptation needs to be understood in terms of probability, and not in strict numbers of molecules. Most importantly, selection of appropriate parameters in this simple linear setting may yield populations of cells displaying adaptation, while single cells do not. Conclusions Single cell behavior cannot be inferred from population measurements and, sometimes, collective behavior cannot be determined from the individuals. By consequence, adaptation can many times be considered a purely emergent property of the collective system. This is a clear example where biological ergodicity cannot be assumed, just as is also the case when cell replication rates are not homogeneous, or depend on the cell state. Our analysis shows, for the first time, how ergodicity cannot be taken for granted in simple linear examples either. The latter holds even when cells are considered isolated and devoid of replication capabilities (cell-cycle arrested. We also show how a simple linear adaptation scheme displays fold-change detection properties, and how rupture of ergodicity prevails in scenarios where transitions between

  18. Adaptive function projective synchronization of two-cell Quantum-CNN chaotic oscillators with uncertain parameters

    International Nuclear Information System (INIS)

    Sudheer, K. Sebastian; Sabir, M.

    2009-01-01

    This work investigates function projective synchronization of two-cell Quantum-CNN chaotic oscillators using adaptive method. Quantum-CNN oscillators produce nano scale chaotic oscillations under certain conditions. By Lyapunove stability theory, the adaptive control law and the parameter update law are derived to make the state of two chaotic systems function projective synchronized. Numerical simulations are presented to demonstrate the effectiveness of the proposed adaptive controllers.

  19. AAV delivery of GRP78/BiP promotes adaptation of human RPE cell to ER stress.

    Science.gov (United States)

    Ghaderi, Shima; Ahmadian, Shahin; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Samiei, Shahram; Kheitan, Samira; Pirmardan, Ehsan R

    2018-02-01

    Adeno associated virus (AAV)-mediated gene delivery of GRP78 (78 kDa glucose-regulated protein) attenuates the condition of endoplasmic reticulum (ER) stress and prevents apoptotic loss of photoreceptors in Retinitis pigmentosa (RP) rats. In the current study we overexpressed Grp78 with the help of AAV-2 in primary human retinal pigmented epithelium (hRPE) cell cultures and examined its effect on cell response to ER stress. The purpose of this work was studying potential stimulating effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress, as an in vitro model for RPE degeneration. To investigate the effect of Grp78 overexpression on unfolded protein response (UPR) markers under ER stress, hRPE primary cultures were transduced by recombinant virus rAAV/Grp78, and treated with ER stressor drug, tunicamycin. Expression changes of four UPR markers including GRP78, PERK, ATF6α, and GADD153/CHOP, were assessed by real-time PCR and western blotting. We found that GRP78 has a great contribution in modulation of UPR markers to favor adaptive response in ER-stressed hRPE cells. In fact, GRP78 overexpression affected adaptation and apoptotic phases of early UPR, through enhancement of two master regulators/ER stress sensors (PERK and ATF6α) and down-regulation of a key pro-apoptotic cascade activator (GADD153/CHOP). Together these findings demonstrate the promoting effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress. This protein with anti-apoptotic actions in the early UPR and important role in cell fate regulation, can be recruited as a useful candidate for future investigations of RPE degenerative diseases. © 2017 Wiley Periodicals, Inc.

  20. Underwater Image Enhancement by Adaptive Gray World and Differential Gray-Levels Histogram Equalization

    Directory of Open Access Journals (Sweden)

    WONG, S.-L.

    2018-05-01

    Full Text Available Most underwater images tend to be dominated by a single color cast. This paper presents a solution to remove the color cast and improve the contrast in underwater images. However, after the removal of the color cast using Gray World (GW method, the resultant image is not visually pleasing. Hence, we propose an integrated approach using Adaptive GW (AGW and Differential Gray-Levels Histogram Equalization (DHE that operate in parallel. The AGW is applied to remove the color cast while DHE is used to improve the contrast of the underwater image. The outputs of both chromaticity components of AGW and intensity components of DHE are combined to form the enhanced image. The results of the proposed method are compared with three existing methods using qualitative and quantitative measures. The proposed method increased the visibility of underwater images and in most cases produces better quantitative scores when compared to the three existing methods.

  1. Prediction of ultrasonic pulse velocity for enhanced peat bricks using adaptive neuro-fuzzy methodology.

    Science.gov (United States)

    Motamedi, Shervin; Roy, Chandrabhushan; Shamshirband, Shahaboddin; Hashim, Roslan; Petković, Dalibor; Song, Ki-Il

    2015-08-01

    Ultrasonic pulse velocity is affected by defects in material structure. This study applied soft computing techniques to predict the ultrasonic pulse velocity for various peats and cement content mixtures for several curing periods. First, this investigation constructed a process to simulate the ultrasonic pulse velocity with adaptive neuro-fuzzy inference system. Then, an ANFIS network with neurons was developed. The input and output layers consisted of four and one neurons, respectively. The four inputs were cement, peat, sand content (%) and curing period (days). The simulation results showed efficient performance of the proposed system. The ANFIS and experimental results were compared through the coefficient of determination and root-mean-square error. In conclusion, use of ANFIS network enhances prediction and generation of strength. The simulation results confirmed the effectiveness of the suggested strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Adaptive enhancement of optical fringe patterns by selective reconstruction using FABEMD algorithm and Hilbert spiral transform.

    Science.gov (United States)

    Trusiak, Maciej; Patorski, Krzysztof; Wielgus, Maciej

    2012-10-08

    Presented method for fringe pattern enhancement has been designed for processing and analyzing low quality fringe patterns. It uses a modified fast and adaptive bidimensional empirical mode decomposition (FABEMD) for the extraction of bidimensional intrinsic mode functions (BIMFs) from an interferogram. Fringe pattern is then selectively reconstructed (SR) taking the regions of selected BIMFs with high modulation values only. Amplitude demodulation and normalization of the reconstructed image is conducted using the spiral phase Hilbert transform (HS). It has been tested using computer generated interferograms and real data. The performance of the presented SR-FABEMD-HS method is compared with other normalization techniques. Its superiority, potential and robustness to high fringe density variations and the presence of noise, modulation and background illumination defects in analyzed fringe patterns has been corroborated.

  3. Enhanced L-(+)-lactic acid production by an adapted strain of Rhizopus oryzae using corncob hydrolysate

    DEFF Research Database (Denmark)

    Bai, Dongmei; Li, S.Z.; Liu, Z.L.

    2008-01-01

    -added production of a variety of bioproducts. Lactic acid can be used as a precursor for poly-lactic acid production. Although current industrial lactic acid is produced by lactic acid bacteria using enriched medium, production by Rhizopus oryzae is preferred due to its exclusive formation of the......-isomer and a simple nutrition requirement by the fungus. Production of-L-(+)-lactic acid by R. oryzae using xylose has been reported; however, its yield and conversion rate are poor compared with that of using glucose. In this study, we report an adapted R. oryzae strain HZS6 that significantly improved efficiency...... of substrate utilization and enhanced production of L-(+)-lactic acid from corncob hydrolysate. It increased L-(+)-lactic acid final concentration, yield, and volumetric productivity more than twofold compared with its parental strain. The optimized growth and fermentation conditions for Strain HZS6 were...

  4. Adaptive intervention design in mobile health: Intervention design and development in the Cell Phone Intervention for You trial.

    Science.gov (United States)

    Lin, Pao-Hwa; Intille, Stephen; Bennett, Gary; Bosworth, Hayden B; Corsino, Leonor; Voils, Corrine; Grambow, Steven; Lazenka, Tony; Batch, Bryan C; Tyson, Crystal; Svetkey, Laura P

    2015-12-01

    The obesity epidemic has spread to young adults, and obesity is a significant risk factor for cardiovascular disease. The prominence and increasing functionality of mobile phones may provide an opportunity to deliver longitudinal and scalable weight management interventions in young adults. The aim of this article is to describe the design and development of the intervention tested in the Cell Phone Intervention for You study and to highlight the importance of adaptive intervention design that made it possible. The Cell Phone Intervention for You study was a National Heart, Lung, and Blood Institute-sponsored, controlled, 24-month randomized clinical trial comparing two active interventions to a usual-care control group. Participants were 365 overweight or obese (body mass index≥25 kg/m2) young adults. Both active interventions were designed based on social cognitive theory and incorporated techniques for behavioral self-management and motivational enhancement. Initial intervention development occurred during a 1-year formative phase utilizing focus groups and iterative, participatory design. During the intervention testing, adaptive intervention design, where an intervention is updated or extended throughout a trial while assuring the delivery of exactly the same intervention to each cohort, was employed. The adaptive intervention design strategy distributed technical work and allowed introduction of novel components in phases intended to help promote and sustain participant engagement. Adaptive intervention design was made possible by exploiting the mobile phone's remote data capabilities so that adoption of particular application components could be continuously monitored and components subsequently added or updated remotely. The cell phone intervention was delivered almost entirely via cell phone and was always-present, proactive, and interactive-providing passive and active reminders, frequent opportunities for knowledge dissemination, and multiple tools

  5. Cellular plasticity enables adaptation to unforeseen cell-cycle rewiring challenges.

    Directory of Open Access Journals (Sweden)

    Yair Katzir

    Full Text Available The fundamental dynamics of the cell cycle, underlying cell growth and reproduction, were previously found to be robust under a wide range of environmental and internal perturbations. This property was commonly attributed to its network structure, which enables the coordinated interactions among hundreds of proteins. Despite significant advances in deciphering the components and autonomous interactions of this network, understanding the interfaces of the cell cycle with other major cellular processes is still lacking. To gain insight into these interfaces, we used the process of genome-rewiring in yeast by placing an essential metabolic gene HIS3 from the histidine biosynthesis pathway, under the exclusive regulation of different cell-cycle promoters. In a medium lacking histidine and under partial inhibition of the HIS3p, the rewired cells encountered an unforeseen multitasking challenge; the cell-cycle regulatory genes were required to regulate the essential histidine-pathway gene in concert with the other metabolic demands, while simultaneously driving the cell cycle through its proper temporal phases. We show here that chemostat cell populations with rewired cell-cycle promoters adapted within a short time to accommodate the inhibition of HIS3p and stabilized a new phenotypic state. Furthermore, a significant fraction of the population was able to adapt and grow into mature colonies on plates under such inhibiting conditions. The adapted state was shown to be stably inherited across generations. These adaptation dynamics were accompanied by a non-specific and irreproducible genome-wide transcriptional response. Adaptation of the cell-cycle attests to its multitasking capabilities and flexible interface with cellular metabolic processes and requirements. Similar adaptation features were found in our previous work when rewiring HIS3 to the GAL system and switching cells from galactose to glucose. Thus, at the basis of cellular plasticity is

  6. Cellular plasticity enables adaptation to unforeseen cell-cycle rewiring challenges.

    Science.gov (United States)

    Katzir, Yair; Stolovicki, Elad; Stern, Shay; Braun, Erez

    2012-01-01

    The fundamental dynamics of the cell cycle, underlying cell growth and reproduction, were previously found to be robust under a wide range of environmental and internal perturbations. This property was commonly attributed to its network structure, which enables the coordinated interactions among hundreds of proteins. Despite significant advances in deciphering the components and autonomous interactions of this network, understanding the interfaces of the cell cycle with other major cellular processes is still lacking. To gain insight into these interfaces, we used the process of genome-rewiring in yeast by placing an essential metabolic gene HIS3 from the histidine biosynthesis pathway, under the exclusive regulation of different cell-cycle promoters. In a medium lacking histidine and under partial inhibition of the HIS3p, the rewired cells encountered an unforeseen multitasking challenge; the cell-cycle regulatory genes were required to regulate the essential histidine-pathway gene in concert with the other metabolic demands, while simultaneously driving the cell cycle through its proper temporal phases. We show here that chemostat cell populations with rewired cell-cycle promoters adapted within a short time to accommodate the inhibition of HIS3p and stabilized a new phenotypic state. Furthermore, a significant fraction of the population was able to adapt and grow into mature colonies on plates under such inhibiting conditions. The adapted state was shown to be stably inherited across generations. These adaptation dynamics were accompanied by a non-specific and irreproducible genome-wide transcriptional response. Adaptation of the cell-cycle attests to its multitasking capabilities and flexible interface with cellular metabolic processes and requirements. Similar adaptation features were found in our previous work when rewiring HIS3 to the GAL system and switching cells from galactose to glucose. Thus, at the basis of cellular plasticity is the emergence of a yet

  7. Adaptive enhancement of learning protocol in hippocampal cultured networks grown on multielectrode arrays

    Science.gov (United States)

    Pimashkin, Alexey; Gladkov, Arseniy; Mukhina, Irina; Kazantsev, Victor

    2013-01-01

    Learning in neuronal networks can be investigated using dissociated cultures on multielectrode arrays supplied with appropriate closed-loop stimulation. It was shown in previous studies that weakly respondent neurons on the electrodes can be trained to increase their evoked spiking rate within a predefined time window after the stimulus. Such neurons can be associated with weak synaptic connections in nearby culture network. The stimulation leads to the increase in the connectivity and in the response. However, it was not possible to perform the learning protocol for the neurons on electrodes with relatively strong synaptic inputs and responding at higher rates. We proposed an adaptive closed-loop stimulation protocol capable to achieve learning even for the highly respondent electrodes. It means that the culture network can reorganize appropriately its synaptic connectivity to generate a desired response. We introduced an adaptive reinforcement condition accounting for the response variability in control stimulation. It significantly enhanced the learning protocol to a large number of responding electrodes independently on its base response level. We also found that learning effect preserved after 4–6 h after training. PMID:23745105

  8. Planetary gearbox fault feature enhancement based on combined adaptive filter method

    Directory of Open Access Journals (Sweden)

    Shuangshu Tian

    2015-12-01

    Full Text Available The reliability of vibration signals acquired from a planetary gear system (the indispensable part of wind turbine gearbox is directly related to the accuracy of fault diagnosis. The complex operation environment leads to lots of interference signals which are included in the vibration signals. Furthermore, both multiple gears meshing with each other and the differences in transmission rout produce strong nonlinearity in the vibration signals, which makes it difficult to eliminate the noise. This article presents a combined adaptive filter method by taking a delayed signal as reference signal, the Self-Adaptive Noise Cancellation method is adopted to eliminate the white noise. In the meanwhile, by applying Gaussian function to transform the input signal into high-dimension feature-space signal, the kernel least mean square algorithm is used to cancel the nonlinear interference. Effectiveness of the method has been verified by simulation signals and test rig signals. By dealing with simulation signal, the signal-to-noise ratio can be improved around 30 dB (white noise and the amplitude of nonlinear interference signal can be depressed up to 50%. Experimental results show remarkable improvements and enhance gear fault features.

  9. Does enhanced heat resistance of irradiated insects represent greater ability to adapt

    International Nuclear Information System (INIS)

    Ducoff, H.S.; MacDuff, R.A.

    1985-01-01

    Previous work from this lab demonstrated that irradiated flour beetles (Tribolium) develop resistance to oxygen with similar kinetics: greater sensitivity for about 1 week, increasing resistance over the next week, and resistance persisting for 3-6 months. This is in contrast to the rapid development of heat resistance in yeast exposed to UV or ionizing radiation and to rapid induction of heat-stress proteins in E. coli exposed to UV or nalidixic acid. The authors' early work did not distinguish between intrinsic heat resistance and enhanced ability to adapt. They tried to resolve this problem by comparing response of irradiated and of control beetles to challenge at 45 0 C with or without brief exposure to 41 0 C just prior to challenge. Mean lethal exposure time at 45 0 C was increased to about the same extent in both populations after 15 min at 41 0 C, suggesting that irradiation increases insectors' intrinsic resistance to stress rather than their ability to adapt

  10. Using Adaptive Tone Mapping to Enhance Edge-Preserving Color Image Automatically

    Directory of Open Access Journals (Sweden)

    Lu Min-Yao

    2010-01-01

    Full Text Available One common characteristic of most high-contrast images is the coexistence of dark shadows and bright light source in one scene. It is very difficult to present details in both dark and bright areas simultaneously on most display devices. In order to resolve this problem, a new method utilizing bilateral filter combined with adaptive tone-mapping method is proposed to improve image quality. First of all, bilateral filter is used to decompose image into two layers: large-scale layer and detail layer. Then, the large-scale layer image is divided into three regions: bright, mid-tone, and dark region. Finally, an appropriate tone-mapping method is chosen to process each region according to its individual property. Only large-scale layer image is enhanced by using adaptive tone mapping; therefore, the details of the original image can be preserved. The experiment results demonstrate the success of proposed method. Furthermore, the proposed method can also avoid posterization produced by methods using histogram equalization.

  11. Adaptive Learning in Medical Education: The Final Piece of Technology Enhanced Learning?

    Science.gov (United States)

    Sharma, Neel; Doherty, Iain; Dong, Chaoyan

    2017-09-01

    Technology enhanced learning (TEL) is now common practice in the field of medical education. One of the primary examples of its use is that of high fidelity simulation and computerised mannequins. Further examples include online learning modules, electronic portfolios, virtual patient interactions, massive open online courses and the flipped classroom movement. The rise of TEL has occurred primarily due to the ease of internet access enabling the retrieval and sharing of information in an instant. Furthermore, the compact nature of internet ready devices such as smartphones and laptops has meant that access to information can occur anytime and anywhere. From an educational perspective however, the current utilisation of TEL has been hindered by its lack of understanding of learners' needs. This is concerning, particularly as evidence highlights that during medical training, each individual learner has their own learning requirements and often achieves competency at different rates. In view of this, there has been interest in ensuring TEL is more learner aware and that the learning process should be more personalised. Adaptive learning can aim to achieve this by ensuring content is delivered according to the needs of the learner. This commentary highlights the move towards adaptive learning and the benefits of such an intervention.

  12. Adapting a couple-based intimacy enhancement intervention to breast cancer: A developmental study.

    Science.gov (United States)

    Reese, Jennifer Barsky; Porter, Laura S; Casale, Kristen E; Bantug, Elissa T; Bober, Sharon L; Schwartz, Sharon C; Smith, Katherine Clegg

    2016-10-01

    Sexual concerns continue to be poorly addressed for women treated for breast cancer and evidence-based interventions that adequately address these concerns are scarce. The objective of this study was to adapt a telephone-based intimacy enhancement intervention, previously tested in couples facing colorectal cancer, to the needs of women with breast cancer through qualitative focus groups, cognitive interviews, and expert review. Three semistructured qualitative focus groups in partnered posttreatment breast cancer survivors (n = 15) reporting sexual concerns were conducted to investigate experiences of breast cancer-related sexual concerns and intervention preferences. Focus group data were coded using the framework approach to qualitative analysis; 8 key themes were identified and used to develop the content and format of the intervention. Feedback from cognitive interviews with study-naïve breast cancer survivors (n = 4) and expert review of materials were also incorporated in finalizing the intervention materials. Qualitative findings centered on the impact of breast cancer and its treatment on women's sexuality and on the intimate relationship, experiences of helpful and unhelpful coping methods, and explicit intervention preferences. Focus group data were particularly helpful in identifying the scope of educational topics and in determining how to structure intervention skills practice (e.g., intimacy-related communication) to be optimally relevant and helpful for both women and their partners. Cognitive interview feedback helped refine intervention materials. An intimacy enhancement intervention was adapted for women with breast cancer and their partners. This intervention offers a promising, potentially disseminable approach to addressing breast cancer-related sexual concerns. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  13. The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk.

    Science.gov (United States)

    Gabrielli, Sara; Ortolani, Claudio; Del Zotto, Genny; Luchetti, Francesca; Canonico, Barbara; Buccella, Flavia; Artico, Marco; Papa, Stefano; Zamai, Loris

    2016-01-01

    Although NK cells are considered part of the innate immune system, a series of evidences has demonstrated that they possess characteristics typical of the adaptive immune system. These NK adaptive features, in particular their memory-like functions, are discussed from an ontogenetic and evolutionary point of view.

  14. The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

    Directory of Open Access Journals (Sweden)

    Sara Gabrielli

    2016-01-01

    Full Text Available Although NK cells are considered part of the innate immune system, a series of evidences has demonstrated that they possess characteristics typical of the adaptive immune system. These NK adaptive features, in particular their memory-like functions, are discussed from an ontogenetic and evolutionary point of view.

  15. A stressful microenvironment: opposing effects of the endoplasmic reticulum stress response in the suppression and enhancement of adaptive tumor immunity.

    Science.gov (United States)

    Rausch, Matthew P; Sertil, Aparna Ranganathan

    2015-03-01

    The recent clinical success of immunotherapy in the treatment of certain types of cancer has demonstrated the powerful ability of the immune system to control tumor growth, leading to significantly improved patient survival. However, despite these promising results current immunotherapeutic strategies are still limited and have not yet achieved broad acceptance outside the context of metastatic melanoma. The limitations of current immunotherapeutic approaches can be attributed in part to suppressive mechanisms present in the tumor microenvironment that hamper the generation of robust antitumor immune responses thus allowing tumor cells to escape immune-mediated destruction. The endoplasmic reticulum (ER) stress response has recently emerged as a potent regulator of tumor immunity. The ER stress response is an adaptive mechanism that allows tumor cells to survive in the harsh growth conditions inherent to the tumor milieu such as low oxygen (hypoxia), low pH and low levels of glucose. Activation of ER stress can also alter the cancer cell response to therapies. In addition, the ER stress response promotes tumor immune evasion by inducing the production of protumorigenic inflammatory cytokines and impairing tumor antigen presentation. However, the ER stress response can boost antitumor immunity in some situations by enhancing the processing and presentation of tumor antigens and by inducing the release of immunogenic factors from stressed tumor cells. Here, we discuss the dualistic role of the ER stress response in the modulation of tumor immunity and highlight how strategies to either induce or block ER stress can be employed to improve the clinical efficacy of tumor immunotherapy.

  16. Resveratrol Enhances Self-Renewal of Mouse Embryonic Stem Cells.

    Science.gov (United States)

    Li, Na; Du, Zhaoyu; Shen, Qiaoyan; Lei, Qijing; Zhang, Ying; Zhang, Mengfei; Hua, Jinlian

    2017-07-01

    Resveratrol (RSV) has been shown to affect the differentiation of several types of stem cells, while the detailed mechanism is elusive. Here, we aim to investigate the function of RSV in self-renewal of mouse embryonic stem cells (ESCs) and the related mechanisms. In contrast with its reported roles, we found unexpectedly that differentiated ESCs or iPSCs treated by RSV would not show further differentiation, but regained a naïve pluripotency state with higher expressions of core transcriptional factors and with the ability to differentiate into all three germ layers when transplanted in vivo. In accordance with these findings, RSV also enhanced cell cycle progression of ESCs via regulating cell cycle-related proteins. Finally, enhanced activation of JAK/STAT3 signaling pathway and suppressed activation of mTOR were found essential in enhancing the self-renewal of ESCs by RSV. Our finding discovered a novel function of RSV in enhancing the self-renewal of ESCs, and suggested that the timing of treatment and concentration of RSV determined the final effect of it. Our work may contribute to understanding of RSV in the self-renewal maintenance of pluripotent stem cells, and may also provide help to the generation and maintenance of iPSCs in vitro. J. Cell. Biochem. 118: 1928-1935, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Enhanced Photovoltaic Properties of Gradient Doping Solar Cells

    International Nuclear Information System (INIS)

    Zhang Chun-Lei; Du Hui-Jing; Zhu Jian-Zhuo; Xu Tian-Fu; Fang Xiao-Yong

    2012-01-01

    An optimum design of a-Si:H(n)/a-Si:H(i)/c-Si(p) heterojunction solar cell is realized with 24.27% conversion efficiency by gradient doping of the a-Si:H(n) layer. The photovoltaic properties are simulated by the AFORSHET software. Besides the additional electric field caused by the gradient doping, the enhanced and widen spectral response also improves the solar cell performance compared with the uniform-doping mode. The simulation shows that the gradient doping is efficient to improve the photovoltaic performance of the solar cells. The study is valuable for the solar cell design with excellent performances

  18. Thermodynamics of photon-enhanced thermionic emission solar cells

    International Nuclear Information System (INIS)

    Reck, Kasper; Hansen, Ole

    2014-01-01

    Photon-enhanced thermionic emission (PETE) cells in which direct photon energy as well as thermal energy can be harvested have recently been suggested as a new candidate for high efficiency solar cells. Here, we present an analytic thermodynamical model for evaluation of the efficiency of PETE solar cells including an analysis of the entropy production due to thermionic emission of general validity. The model is applied to find the maximum efficiency of a PETE cell for given cathode and anode work functions and temperatures

  19. Mast Cells Can Enhance Resistance to Snake and Honeybee Venoms

    Science.gov (United States)

    Metz, Martin; Piliponsky, Adrian M.; Chen, Ching-Cheng; Lammel, Verena; Åbrink, Magnus; Pejler, Gunnar; Tsai, Mindy; Galli, Stephen J.

    2006-07-01

    Snake or honeybee envenomation can cause substantial morbidity and mortality, and it has been proposed that the activation of mast cells by snake or insect venoms can contribute to these effects. We show, in contrast, that mast cells can significantly reduce snake-venom-induced pathology in mice, at least in part by releasing carboxypeptidase A and possibly other proteases, which can degrade venom components. Mast cells also significantly reduced the morbidity and mortality induced by honeybee venom. These findings identify a new biological function for mast cells in enhancing resistance to the morbidity and mortality induced by animal venoms.

  20. Cytogenetic adaptive response induced by pre-exposure in human lymphocytes and marrow cells of mice

    International Nuclear Information System (INIS)

    Zhang Lianzhen; Deng Zhicheng

    1993-01-01

    The cytogenetic adaptive response induced by pre-exposure in human lymphocytes and marrow cells of mice were studied. The results of this study showed that human lymphocytes in vitro and mouse marrow cells in vivo can become adapted to low-level irradiation from 3 H-TdR or exposure to a low dose of X-or γ-irradiation, so that they become less sensitive to the chromosomal damage effects of subsequent exposures. (4 tabs.)

  1. Short-term stress enhances cellular immunity and increases early resistance to squamous cell carcinoma.

    Science.gov (United States)

    Dhabhar, Firdaus S; Saul, Alison N; Daugherty, Christine; Holmes, Tyson H; Bouley, Donna M; Oberyszyn, Tatiana M

    2010-01-01

    In contrast to chronic/long-term stress that suppresses/dysregulates immune function, an acute/short-term fight-or-flight stress response experienced during immune activation can enhance innate and adaptive immunity. Moderate ultraviolet-B (UV) exposure provides a non-invasive system for studying the naturalistic emergence, progression and regression of squamous cell carcinoma (SCC). Because SCC is an immunoresponsive cancer, we hypothesized that short-term stress experienced before UV exposure would enhance protective immunity and increase resistance to SCC. Control and short-term stress groups were treated identically except that the short-term stress group was restrained (2.5h) before each of nine UV-exposure sessions (minimum erythemal dose, 3-times/week) during weeks 4-6 of the 10-week UV exposure protocol. Tumors were measured weekly, and tissue collected at weeks 7, 20, and 32. Chemokine and cytokine gene expression was quantified by real-time PCR, and CD4+ and CD8+ T cells by flow cytometry and immunohistochemistry. Compared to controls, the short-term stress group showed greater cutaneous T-cell attracting chemokine (CTACK)/CCL27, RANTES, IL-12, and IFN-gamma gene expression at weeks 7, 20, and 32, higher skin infiltrating T cell numbers (weeks 7 and 20), lower tumor incidence (weeks 11-20) and fewer tumors (weeks 11-26). These results suggest that activation of short-term stress physiology increased chemokine expression and T cell trafficking and/or function during/following UV exposure, and enhanced Type 1 cytokine-driven cell-mediated immunity that is crucial for resistance to SCC. Therefore, the physiological fight-or-flight stress response and its adjuvant-like immuno-enhancing effects, may provide a novel and important mechanism for enhancing immune system mediated tumor-detection/elimination that merits further investigation.

  2. Materials That Enhance Efficiency and Radiation Resistance of Solar Cells

    Science.gov (United States)

    Sun, Xiadong; Wang, Haorong

    2012-01-01

    A thin layer (approximately 10 microns) of a novel "transparent" fluorescent material is applied to existing solar cells or modules to effectively block and convert UV light, or other lower solar response waveband of solar radiation, to visible or IR light that can be more efficiently used by solar cells for additional photocurrent. Meanwhile, the layer of fluorescent coating material remains fully "transparent" to the visible and IR waveband of solar radiation, resulting in a net gain of solar cell efficiency. This innovation alters the effective solar spectral power distribution to which an existing cell gets exposed, and matches the maximum photovoltaic (PV) response of existing cells. By shifting a low PV response waveband (e.g., UV) of solar radiation to a high PV response waveband (e.g. Vis-Near IR) with novel fluorescent materials that are transparent to other solar-cell sensitive wavebands, electrical output from solar cells will be enhanced. This approach enhances the efficiency of solar cells by converting UV and high-energy particles in space that would otherwise be wasted to visible/IR light. This innovation is a generic technique that can be readily implemented to significantly increase efficiencies of both space and terrestrial solar cells, without incurring much cost, thus bringing a broad base of economical, social, and environmental benefits. The key to this approach is that the "fluorescent" material must be very efficient, and cannot block or attenuate the "desirable" and unconverted" waveband of solar radiation (e.g. Vis-NIR) from reaching the cells. Some nano-phosphors and novel organometallic complex materials have been identified that enhance the energy efficiency on some state-of-the-art commercial silicon and thin-film-based solar cells by over 6%.

  3. Adaptive memory: young children show enhanced retention of fitness-related information.

    Science.gov (United States)

    Aslan, Alp; Bäuml, Karl-Heinz T

    2012-01-01

    Evolutionary psychologists propose that human cognition evolved through natural selection to solve adaptive problems related to survival and reproduction, with its ultimate function being the enhancement of reproductive fitness. Following this proposal and the evolutionary-developmental view that ancestral selection pressures operated not only on reproductive adults, but also on pre-reproductive children, the present study examined whether young children show superior memory for information that is processed in terms of its survival value. In two experiments, we found such survival processing to enhance retention in 4- to 10-year-old children, relative to various control conditions that also required deep, meaningful processing but were not related to survival. These results suggest that, already in very young children, survival processing is a special and extraordinarily effective form of memory encoding. The results support the functional-evolutionary proposal that young children's memory is "tuned" to process and retain fitness-related information. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Plasmonic Organic Photovoltaics: Unraveling Plasmonic Enhancement for Realistic Cell Geometries

    DEFF Research Database (Denmark)

    Beliatis, Michail

    2018-01-01

    Incorporating plasmonic nanoparticles in organic photovoltaic (OPV) devices can increase the optical thickness of the organic absorber layer while keeping its physical thickness small. However, trade-offs between various structure parameters have caused contradictions regarding the effectiveness...... of plasmonics in the literature, that have somewhat stunted the progressing of a unified theoretical understanding for practical applications. We examine the optical enhancement mechanisms of practical PCDTBT:PC70BM OPV cells incorporating metal nanoparticles. The plasmonic near- and far-field contributions...... show that an already optimized PCDTBT:PC70BM cell can be further optically enhanced by plasmonic effects by at least 20% with the incorporation of Ag nanoparticles....

  5. Investigation of the response of low-dose irradiated cells. Pt. 2. Radio-adaptive response of human embryonic cells is related to cell-to-cell communication

    International Nuclear Information System (INIS)

    Ishii, Keiichiro; Watanabe, Masami.

    1994-01-01

    To clarify the radio-adaptive response of normal cells to low-dose radiation, we irradiated human embryonic cells and HeLa cells with low-dose X-ray and examined the changes in sensitivity to subsequent high-dose X-irradiation. The results obtained were as follows; (1) When HE cells were irradiated by a high-dose of 200 cGy, the growth ratio of the living cells five days after the irradiation decreased to 37% of that of the cells which received no X-irradiation. When the cells received a preliminary irradiation of 10 to 20 cGy four hours before the irradiation of 200 cGy, the relative growth ratios increased significantly to 45-53%. (2) This preliminary irradiation effect was not observed in HeLa cells, being cancer cells. (3) When the HE cells suspended in a Ca 2+ iron-free medium or TPA added medium while receiving the preliminary irradiation of 13 cGy, the effect of the preliminary irradiation in increasing the relative growth ratio of living cells was not observed. (4) This indicates that normal cells shows an adaptive response to low-dose radiation and become more radioresistant. This phenomenon is considered to involve cell-to-cell communication maintained in normal cells and intracellular signal transduction in which Ca 2+ ion plays a role. (author)

  6. HIV-1 adaptation to NK cell-mediated immune pressure

    DEFF Research Database (Denmark)

    Elemans, Marjet; Boelen, Lies; Rasmussen, Michael

    2017-01-01

    The observation, by Alter et al., of the enrichment of NK cell “escape” variants in individuals carrying certain Killer-cell Immunoglobulin-like Receptor (KIR) genes is compelling evidence that natural killer (NK) cells exert selection pressure on HIV-1. Alter et al hypothesise that variant pepti...

  7. Adaptive response to ionizing radiation induced by low doses of gamma rays in human cell lines

    International Nuclear Information System (INIS)

    Seong, Jinsil; Chang, Ok Suh; Gwi, Eon Kim

    1995-01-01

    Purpose: The aim of this study was to investigate whether the adaptive response could be induced in human lymphoblastoid cell lines and human tumor cell lines. The time necessary for the expression of the adaptive response was also investigated. Materials and Methods: Three lymphoblastoid cell lines from ataxia telangiectasia (AT) homozygote (GM 1526), AT heterozygote (GM 3382), and normal individual (3402p) and two hepatoma cell lines, Hep G2 and Hep 3B, were used in this study. Experiments were carried out by delivering 0.01 Gy followed by 0.5 Gy of gamma radiation to the exponentially growing cells. The time necessary for the expression of the adaptive response was determined by varying the time interval between the two doses from 1 to 72 h. In some experiments, 3-aminobenzamide, a potent inhibitor of poly (ADP-ribose) polymerase, was added immediately after the 0.5 Gy exposure. The cultures were fixed 30 min (for the G 2 chromatid) and 6 h (for the S chromatid) after the 0.5 Gy exposure. Metaphase chromosome assay was carried out to score chromatid breaks as an end point. Results: A prior exposure to 0.01 Gy of gamma rays significantly reduced the number of chromatid breaks induced by subsequent higher doses (0.5 Gy) in all the tested cell lines. The magnitude of the adaptive response was similar among the cell lines despite their different radiosensitivities. In the G 2 chromatids, the adaptive response was observed both at short-time intervals, as early as 1 h, and at long-time intervals. In the S chromatids, however, the adaptive response was shown only at long-time intervals. When 3-aminobenzamide was added after the 0.5 Gy, the adaptive responses were abolished in all the experimental groups. Conclusion: The adaptive response was observed in human lymphoblastoid cell lines and hepatoma cell lines. The magnitude of the adaptive response did not seem to be related to the radiosensitivity of the cells. The elimination of the adaptive response with 3

  8. Surface enhanced Raman spectroscopy measurements of MCF7 cells adhesion in confined micro-environments

    KAUST Repository

    De Vitis, Stefania

    2015-05-01

    Undoubtedly cells can perceive the external environment, not only from a biochemical point of view with the related signalling pathways, but also from a physical and topographical perspective. In this sense controlled three dimensional micro-structures as well as patterns at the nano-scale can affect and guide the cell evolution and proliferation, due to the fact that the surrounding environment is no longer isotropic (like the flat surfaces of standard cell culturing) but possesses well defined symmetries and anisotropies. In this work regular arrays of silicon micro-pillars with hexagonal arrangement are used as culturing substrates for MCF-7 breast cancer cells. The characteristic size and spacing of the pillars are tens of microns, comparable with MCF-7 cell dimensions and then well suited to induce acceptable external stimuli. It is shown that these cells strongly modify their morphology for adapting themselves to the micro-structured landscape, by means of protrusions from the main body of the cell. Scanning electron microscopy along with both Raman micro-spectroscopy and surface enhanced Raman spectroscopy are used for topographical and biochemical studies of the new cell arrangement. We have revealed that single MCF-7 cells exploit their capability to produce invadopodia, usually generated to invade the neighboring tissue in metastatic activity, for spanning and growing across separate pillars. © 2015 Elsevier Ltd.

  9. Cytoplasmic Flow Enhances Organelle Dispersion in Eukaryotic Cells

    Science.gov (United States)

    Koslover, Elena; Mogre, Saurabh; Chan, Caleb; Theriot, Julie

    The cytoplasm of a living cell is an active environment through which intracellular components move and mix. We explore, using theoretical modeling coupled with microrheological measurements, the efficiency of particle dispersion via different modes of transport within this active environment. In particular, we focus on the role of cytoplasmic flow over different scales in contributing to organelle transport within two different cell types. In motile neutrophil cells, we show that bulk fluid flow associated with rapid cell deformation enhances particle transport to and from the cell periphery. In narrow fungal hyphae, localized flows due to hydrodynamic entrainment are shown to contribute to optimally efficient organelle dispersion. Our results highlight the importance of non-traditional modes of transport associated with flow of the cytoplasmic fluid in the distribution of organelles throughout eukaryotic cells.

  10. Adaptive and Pathogenic Responses to Stress by Stem Cells during Development

    OpenAIRE

    Mansouri, Ladan; Xie, Yufen; Rappolee, Daniel A

    2012-01-01

    Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induce...

  11. Enhanced 3D fluorescence live cell imaging on nanoplasmonic substrate

    International Nuclear Information System (INIS)

    Gartia, Manas Ranjan; Hsiao, Austin; Logan Liu, G; Sivaguru, Mayandi; Chen Yi

    2011-01-01

    We have created a randomly distributed nanocone substrate on silicon coated with silver for surface-plasmon-enhanced fluorescence detection and 3D cell imaging. Optical characterization of the nanocone substrate showed it can support several plasmonic modes (in the 300-800 nm wavelength range) that can be coupled to a fluorophore on the surface of the substrate, which gives rise to the enhanced fluorescence. Spectral analysis suggests that a nanocone substrate can create more excitons and shorter lifetime in the model fluorophore Rhodamine 6G (R6G) due to plasmon resonance energy transfer from the nanocone substrate to the nearby fluorophore. We observed three-dimensional fluorescence enhancement on our substrate shown from the confocal fluorescence imaging of chinese hamster ovary (CHO) cells grown on the substrate. The fluorescence intensity from the fluorophores bound on the cell membrane was amplified more than 100-fold as compared to that on a glass substrate. We believe that strong scattering within the nanostructured area coupled with random scattering inside the cell resulted in the observed three-dimensional enhancement in fluorescence with higher photostability on the substrate surface.

  12. Enhanced 3D fluorescence live cell imaging on nanoplasmonic substrate

    Energy Technology Data Exchange (ETDEWEB)

    Gartia, Manas Ranjan [Department of Nuclear, Plasma and Radiological Engineering, University of Illinois, Urbana, IL 61801 (United States); Hsiao, Austin; Logan Liu, G [Department of Bioengineering, University of Illinois, Urbana, IL 61801 (United States); Sivaguru, Mayandi [Institute for Genomic Biology, University of Illinois, Urbana, IL 61801 (United States); Chen Yi, E-mail: loganliu@illinois.edu [Department of Electrical and Computer Engineering, University of Illinois, Urbana, IL 61801 (United States)

    2011-09-07

    We have created a randomly distributed nanocone substrate on silicon coated with silver for surface-plasmon-enhanced fluorescence detection and 3D cell imaging. Optical characterization of the nanocone substrate showed it can support several plasmonic modes (in the 300-800 nm wavelength range) that can be coupled to a fluorophore on the surface of the substrate, which gives rise to the enhanced fluorescence. Spectral analysis suggests that a nanocone substrate can create more excitons and shorter lifetime in the model fluorophore Rhodamine 6G (R6G) due to plasmon resonance energy transfer from the nanocone substrate to the nearby fluorophore. We observed three-dimensional fluorescence enhancement on our substrate shown from the confocal fluorescence imaging of chinese hamster ovary (CHO) cells grown on the substrate. The fluorescence intensity from the fluorophores bound on the cell membrane was amplified more than 100-fold as compared to that on a glass substrate. We believe that strong scattering within the nanostructured area coupled with random scattering inside the cell resulted in the observed three-dimensional enhancement in fluorescence with higher photostability on the substrate surface.

  13. Ouabain enhances ADPKD cell apoptosis via the intrinsic pathway

    Directory of Open Access Journals (Sweden)

    Gustavo eBlanco

    2016-03-01

    Full Text Available Progression of autosomal dominant polycystic kidney disease (ADPKD is highly influenced by factors circulating in blood. We have shown that the hormone ouabain enhances several characteristics of the ADPKD cystic phenotype, including the rate of cell proliferation, fluid secretion and the capacity of the cells to form cysts. In this work, we found that physiological levels of ouabain (3nM also promote programmed cell death of renal epithelial cells obtained from kidney cysts of patients with ADPKD (ADPKD cells. This was determined by Alexa Fluor 488 labeled-Annexin-V staining and TUNEL assay, both biochemical markers of apoptosis. Ouabain-induced apoptosis also takes place when ADPKD cell growth is blocked; suggesting that the effect is not secondary to the stimulatory actions of ouabain on cell proliferation. Ouabain alters the expression of BCL family of proteins, reducing BCL-2 and increasing BAX expression levels, anti- and pro-apoptotic mediators respectively. In addition, ouabain caused the release of cytochrome c from mitochondria. Moreover, ouabain activates caspase-3, a key executioner caspase in the cell apoptotic pathway, but did not affect caspase-8. This suggests that ouabain triggers ADPKD cell apoptosis by stimulating the intrinsic, but not the extrinsic pathway of programmed cell death. The apoptotic effects of ouabain are specific for ADPKD cells and do not occur in normal human kidney cells (NHK cells. Taken together with our previous observations, these results show that ouabain causes an imbalance in cell growth/death, to favor growth of the cystic cells. This event, characteristic of ADPKD, further suggests the importance of ouabain as a circulating factor that promotes ADPKD progression.

  14. Human tumor cell proliferation evaluated using manganese-enhanced MRI.

    Directory of Open Access Journals (Sweden)

    Rod D Braun

    Full Text Available Tumor cell proliferation can depend on calcium entry across the cell membrane. As a first step toward the development of a non-invasive test of the extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor cell uptake of a calcium surrogate, Mn(2+ [measured with manganese-enhanced MRI (MEMRI], is linked to proliferation rate in vitro.Proliferation rates were determined in vitro in three different human tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate carcinoma. Cells growing at different average proliferation rates were exposed to 1 mM MnCl(2 for one hour and then thoroughly washed. MEMRI R(1 values (longitudinal relaxation rates, which have a positive linear relationship with Mn(2+ concentration, were then determined from cell pellets. Cell cycle distributions were determined using propidium iodide staining and flow cytometry. All three lines showed Mn(2+-induced increases in R(1 compared to cells not exposed to Mn(2+. C918 and PC-3 cells each showed a significant, positive correlation between MEMRI R(1 values and proliferation rate (p≤0.005, while OCM-1 cells showed no significant correlation. Preliminary, general modeling of these positive relationships suggested that pellet R(1 for the PC-3 cells, but not for the C918 cells, could be adequately described by simply accounting for changes in the distribution of the cell cycle-dependent subpopulations in the pellet.These data clearly demonstrate the tumor-cell dependent nature of the relationship between proliferation and calcium influx, and underscore the usefulness of MEMRI as a non-invasive method for investigating this link. MEMRI is applicable to study tumors in vivo, and the present results raise the possibility of evaluating proliferation parameters of some tumor types in vivo using MEMRI.

  15. A New Adaptive Gamma Correction Based Algorithm Using DWT-SVD for Non-Contrast CT Image Enhancement.

    Science.gov (United States)

    Kallel, Fathi; Ben Hamida, Ahmed

    2017-12-01

    The performances of medical image processing techniques, in particular CT scans, are usually affected by poor contrast quality introduced by some medical imaging devices. This suggests the use of contrast enhancement methods as a solution to adjust the intensity distribution of the dark image. In this paper, an advanced adaptive and simple algorithm for dark medical image enhancement is proposed. This approach is principally based on adaptive gamma correction using discrete wavelet transform with singular-value decomposition (DWT-SVD). In a first step, the technique decomposes the input medical image into four frequency sub-bands by using DWT and then estimates the singular-value matrix of the low-low (LL) sub-band image. In a second step, an enhanced LL component is generated using an adequate correction factor and inverse singular value decomposition (SVD). In a third step, for an additional improvement of LL component, obtained LL sub-band image from SVD enhancement stage is classified into two main classes (low contrast and moderate contrast classes) based on their statistical information and therefore processed using an adaptive dynamic gamma correction function. In fact, an adaptive gamma correction factor is calculated for each image according to its class. Finally, the obtained LL sub-band image undergoes inverse DWT together with the unprocessed low-high (LH), high-low (HL), and high-high (HH) sub-bands for enhanced image generation. Different types of non-contrast CT medical images are considered for performance evaluation of the proposed contrast enhancement algorithm based on adaptive gamma correction using DWT-SVD (DWT-SVD-AGC). Results show that our proposed algorithm performs better than other state-of-the-art techniques.

  16. Plasmonic versus dielectric enhancement in thin-film solar cells

    DEFF Research Database (Denmark)

    Dühring, Maria Bayard; Mortensen, N. Asger; Sigmund, Ole

    2012-01-01

    to its metallic counterpart. We show that the enhanced normalized short-circuit current for a cell with silicon strips can be increased 4 times compared to the best performance for strips of silver, gold, or aluminium. For this particular case, the simple dielectric grating may outperform its plasmonic......Several studies have indicated that broadband absorption of thin-film solar cells can be enhanced by use of surface-plasmon induced resonances of metallic parts like strips or particles. The metallic parts may create localized modes or scatter incoming light to increase absorption in thin......-film semiconducting material. For a particular case, we show that coupling to the same type of localized slab-waveguide modes can be obtained by a surface modulation consisting of purely dielectric strips. The purely dielectric device turns out to have a significantly higher broadband enhancement factor compared...

  17. Dynamic Enhanced Inter-Cell Interference Coordination for Realistic Networks

    DEFF Research Database (Denmark)

    Pedersen, Klaus I.; Alvarez, Beatriz Soret; Barcos, Sonia

    2016-01-01

    Enhanced Inter-Cell Interference Coordination (eICIC) is a key ingredient to boost the performance of co-channel Heterogeneous Networks (HetNets). eICIC encompasses two main techniques: Almost Blank Subframes (ABS), during which the macro cell remains silent to reduce the interference, and biased...... and an opportunistic approach exploiting the varying cell conditions. Moreover, an autonomous fast distributed muting algorithm is presented, which is simple, robust, and well suited for irregular network deployments. Performance results for realistic network deployments show that the traditional semi-static e...

  18. Adapting a robotics program to enhance participation and interest in STEM among children with disabilities: a pilot study.

    Science.gov (United States)

    Lindsay, Sally; Hounsell, Kara Grace

    2017-10-01

    Youth with disabilities are under-represented in science, technology, engineering, and math (STEM) in school and in the workforce. One encouraging approach to engage youth's interest in STEM is through robotics; however, such programs are mostly for typically developing youth. The purpose of this study was to understand the development and implementation of an adapted robotics program for children and youth with disabilities and their experiences within it. Our mixed methods pilot study (pre- and post-workshop surveys, observations, and interviews) involved 41 participants including: 18 youth (aged 6-13), 12 parents and 11 key informants. The robotics program involved 6, two-hour workshops held at a paediatric hospital. Our findings showed that several adaptations made to the robotics program helped to enhance the participation of children with disabilities. Adaptations addressed the educational/curriculum, cognitive and learning, physical and social needs of the children. In regards to experiences within the adapted hospital program, our findings highlight that children enjoyed the program and learned about computer programming and building robots. Clinicians and educators should consider engaging youth with disabilities in robotics to enhance learning and interest in STEM. Implications for Rehabilitation Clinicians and educators should consider adapting curriculum content and mode of delivery of LEGO ® robotics programs to include youth with disabilities. Appropriate staffing including clinicians and educators who are knowledgeable about youth with disabilities and LEGO ® robotics are needed. Clinicians should consider engaging youth with disabilities in LEGO ® to enhance learning and interest in STEM.

  19. Murine and bovine γδ T cells enhance innate immunity against Brucella abortus infections.

    Directory of Open Access Journals (Sweden)

    Jerod A Skyberg

    Full Text Available γδ T cells have been postulated to act as a first line of defense against infectious agents, particularly intracellular pathogens, representing an important link between the innate and adaptive immune responses. Human γδ T cells expand in the blood of brucellosis patients and are active against Brucella in vitro. However, the role of γδ T cells in vivo during experimental brucellosis has not been studied. Here we report TCRδ(-/- mice are more susceptible to B. abortus infection than C57BL/6 mice at one week post-infection as measured by splenic colonization and splenomegaly. An increase in TCRγδ cells was observed in the spleens of B. abortus-infected C57BL/6 mice, which peaked at two weeks post-infection and occurred concomitantly with diminished brucellae. γδ T cells were the major source of IL-17 following infection and also produced IFN-γ. Depletion of γδ T cells from C57BL/6, IL-17Rα(-/-, and GMCSF(-/- mice enhanced susceptibility to B. abortus infection although this susceptibility was unaltered in the mutant mice; however, when γδ T cells were depleted from IFN-γ(-/- mice, enhanced susceptibility was observed. Neutralization of γδ T cells in the absence of TNF-α did not further impair immunity. In the absence of TNF-α or γδ T cells, B. abortus-infected mice showed enhanced IFN-γ, suggesting that they augmented production to compensate for the loss of γδ T cells and/or TNF-α. While the protective role of γδ T cells was TNF-α-dependent, γδ T cells were not the major source of TNF-α and activation of γδ T cells following B. abortus infection was TNF-α-independent. Additionally, bovine TCRγδ cells were found to respond rapidly to B. abortus infection upon co-culture with autologous macrophages and could impair the intramacrophage replication of B. abortus via IFN-γ. Collectively, these results demonstrate γδ T cells are important for early protection to B. abortus infections.

  20. Functional adaptation of the human β-cells after frequent exposure to noradrenaline

    DEFF Research Database (Denmark)

    Dela, Flemming

    2015-01-01

    KEY POINTS: Trained people produce less insulin than untrained; there is an adaptation of the insulin-producing cells to the trained state. The mechanism behind this adaptation is not known, but some sort of memory must be introduced into the insulin-producing cells. Here it is shown that this me......KEY POINTS: Trained people produce less insulin than untrained; there is an adaptation of the insulin-producing cells to the trained state. The mechanism behind this adaptation is not known, but some sort of memory must be introduced into the insulin-producing cells. Here it is shown...... that this memory is introduced by 10 daily intravenous infusions of noradrenaline, mimicking the increases that occur during a 10 day training programme. Thus, after the infusion period, the subjects produced less insulin in response to the same stimulus. It is concluded that exercise-induced increases...... in noradrenaline is most likely the stimulus that introduces a memory in the insulin-producing cells. ABSTRACT: Physical training decreases glucose- and arginine-stimulated insulin secretion. The mechanism by which the pancreatic β-cells adapt to the training status of the individual is not known. We hypothesized...

  1. A Distributed Taxation Based Rank Adaptation Scheme for 5G Small Cells

    DEFF Research Database (Denmark)

    Catania, Davide; Cattoni, Andrea Fabio; Mahmood, Nurul Huda

    2015-01-01

    The further densification of small cells impose high and undesirable levels of inter-cell interference. Multiple Input Multiple Output (MIMO) systems along with advanced receiver techniques provide us with extra degrees of freedom to combat such a problem. With such tools, rank adaptation...

  2. Highly adaptable triple-negative breast cancer cells as a functional model for testing anticancer agents.

    Directory of Open Access Journals (Sweden)

    Balraj Singh

    Full Text Available A major obstacle in developing effective therapies against solid tumors stems from an inability to adequately model the rare subpopulation of panresistant cancer cells that may often drive the disease. We describe a strategy for optimally modeling highly abnormal and highly adaptable human triple-negative breast cancer cells, and evaluating therapies for their ability to eradicate such cells. To overcome the shortcomings often associated with cell culture models, we incorporated several features in our model including a selection of highly adaptable cancer cells based on their ability to survive a metabolic challenge. We have previously shown that metabolically adaptable cancer cells efficiently metastasize to multiple organs in nude mice. Here we show that the cancer cells modeled in our system feature an embryo-like gene expression and amplification of the fat mass and obesity associated gene FTO. We also provide evidence of upregulation of ZEB1 and downregulation of GRHL2 indicating increased epithelial to mesenchymal transition in metabolically adaptable cancer cells. Our results obtained with a variety of anticancer agents support the validity of the model of realistic panresistance and suggest that it could be used for developing anticancer agents that would overcome panresistance.

  3. Super-enhancers: Asset management in immune cell genomes.

    Science.gov (United States)

    Witte, Steven; O'Shea, John J; Vahedi, Golnaz

    2015-09-01

    Super-enhancers (SEs) are regions of the genome consisting of clusters of regulatory elements bound with very high amounts of transcription factors, and this architecture appears to be the hallmark of genes and noncoding RNAs linked with cell identity. Recent studies have identified SEs in CD4(+) T cells and have further linked these regions to single nucleotide polymorphisms (SNPs) associated with immune-mediated disorders, pointing to an important role for these structures in the T cell differentiation and function. Here we review the features that define SEs, and discuss their function within the broader understanding of the mechanisms that define immune cell identity and function. We propose that SEs present crucial regulatory hubs, coordinating intrinsic and extrinsic differentiation signals, and argue that delineating these regions will provide important insight into the factors and mechanisms that define immune cell identity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Expression of a highly basic peroxidase gene in NaCl-adapted tomato cell suspensions.

    Science.gov (United States)

    Medina, M I; Botella, M A; Quesada, M A; Valpuesta, V

    1997-05-05

    A tomato peroxidase gene, TPX2, that is only weakly expressed in the roots of young tomato seedlings is highly expressed in tomato suspension cells adapted to high external NaCl concentration. The protein encoded by this gene, with an isolectric point value of approximately 9.6, is found in the culture medium of the growing cells. Our data suggest that the expression of TPX2 in the salt-adapted cells is not the result of the elicitation imposed by the in vitro culture or the presence of high NaCl concentration in the medium.

  5. Scheduled evening sleep and enhanced lighting improve adaptation to night shift work in older adults.

    Science.gov (United States)

    Chinoy, Evan D; Harris, Michael P; Kim, Min Ju; Wang, Wei; Duffy, Jeanne F

    2016-12-01

    We tested whether a sleep and circadian-based treatment shown to improve circadian adaptation to night shifts and attenuate negative effects on alertness, performance and sleep in young adults would also be effective in older adults. We assessed subjective alertness, sustained attention (psychomotor vigilance task, PVT), sleep duration (actigraphy) and circadian timing (salivary dim-light melatonin onset, DLMO) in 18 older adults (57.2±3.8 years; mean±SD) in a simulated shift work protocol. 4 day shifts were followed by 3 night shifts in the laboratory. Participants slept at home and were randomised to either the treatment group (scheduled evening sleep and enhanced lighting during the latter half of night shifts) or control group (ad-lib sleep and typical lighting during night shifts). Compared with day shifts, alertness and sustained attention declined on the first night shift in both groups, and was worse in the latter half of the night shifts. Alertness and attention improved on nights 2 and 3 for the treatment group but remained lower for the control group. Sleep duration in the treatment group remained similar to baseline (6-7 hours) following night shifts, but was shorter (3-5 hours) following night shifts in the control group. Treatment group circadian timing advanced by 169.3±16.1 min (mean±SEM) but did not shift (-9.7±9.9 min) in the control group. The combined treatment of scheduled evening sleep and enhanced lighting increased sleep duration and partially aligned circadian phase with sleep and work timing, resulting in improved night shift alertness and performance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. Performance enhanced DDO-OFDM system with adaptively partitioned precoding and single sideband modulation.

    Science.gov (United States)

    Chen, Xi; Feng, Zhenhua; Tang, Ming; Fu, Songnian; Liu, Deming

    2017-09-18

    As a promising solution for short-to-medium transmission systems, direct detection optical orthogonal frequency division multiplexing (DDO-OFDM) or discrete multi-tone (DMT) has been intensively investigated in last decade. Benefitting from the advantages of peak-to-average power (PAPR) reduction and signal-to-noise ratio (SNR) equalization, precoding techniques are widely applied to enhance the performance of DDO-OFDM systems. However, the conventional method of partitioning precoding sets limits the ability of precoding schemes to optimize the SNR variation and the allocation of modulation formats. Thus, the precoding transmission systems are hard to reach the capacity that traditional bit-power loading (BPL) techniques, like the Levin-Campello (LC) algorithm, can achieve. In this paper, we investigate the principle of SNR variation for precoded DDO-OFDM systems and theoretically demonstrate that the SNR equalization effect of precoding techniques is actually determined by the noise equalization process. Based on this fact, we propose an adaptively partitioned precoding (APP) algorithm to unlock the ability to control the SNR of each subcarrier. As demonstrated by the simulation and experimental results, the proposed APP algorithm achieves the transmission capacity as high as the LC algorithm and has nearly 1 dB PAPR reduction. Besides, the look-up table (LUT) operation ensures low complexity of the proposed APP algorithm compared with LC algorithm. To avoid severe chromatic dispersion (CD) induced spectral fading, single sideband (SSB) modulation is also implemented. We find that SSB modulation can reach the capacity of double sideband (DSB) modulation in optical back-to-back (OB2B) configuration by optimizing the modulation index. Therefore, the APP based SSB-DDO-OFDM scheme can sufficiently enhance the performance of cost-sensitive short-to-medium reach optical fiber communication systems.

  7. Scheduled Evening Sleep and Enhanced Lighting Improve Adaptation to Night Shift Work in Older Adults

    Science.gov (United States)

    Chinoy, Evan D.; Harris, Michael P.; Kim, Min Ju; Wang, Wei; Duffy, Jeanne F.

    2017-01-01

    Objectives We tested whether a sleep and circadian-based treatment shown to improve circadian adaptation to night shifts and attenuate negative effects on alertness, performance, and sleep in young adults would also be effective in older adults. Methods We assessed subjective alertness, sustained attention (psychomotor vigilance task, PVT), sleep duration (actigraphy), and circadian timing (salivary dim-light melatonin onset, DLMO) in eighteen older adults (57.2±3.8 y; mean±SD) in a simulated shift work protocol. Four day shifts were followed by three night shifts in the laboratory. Participants slept at home and were randomized to either the Treatment Group (scheduled evening sleep and enhanced lighting during the latter half of night shifts), or Control Group (ad lib sleep and typical lighting during night shifts). Results Compared to day shifts, alertness and sustained attention declined on the first night shift in both groups, and was worse in the latter half of the night shifts. Alertness and attention improved on nights 2 and 3 for the Treatment Group but remained lower for the Control Group. Sleep duration in the Treatment Group remained similar to baseline (6–7 h) following night shifts, but was shorter (3–5 h) following night shifts in the Control Group. Treatment Group circadian timing advanced by 169.3±16.1 min (mean±SEM) but did not shift (−9.7±9.9 min) in the Control Group. Conclusions The combined treatment of scheduled evening sleep and enhanced lighting increased sleep duration and partially aligned circadian phase with sleep and work timing, resulting in improved night shift alertness and performance. PMID:27566781

  8. 8-aminoadenosine enhances radiation-induced cell death in human lung carcinoma A549 cells

    International Nuclear Information System (INIS)

    Meike, Shunsuke; Yamamori, Tohru; Yasui, Hironobu; Eitaki, Masato; Inanami, Osamu; Matsuda, Akira

    2011-01-01

    The combination of a chemotherapeutic agent and radiation is widely applied to enhance cell death in solid tumor cells in cancer treatment. The purine analogue 8-aminoadenosine (8-NH 2 -Ado) is known to be a transcription inhibitor that has proved very effective in multiple myeloma cell lines and primary indolent leukemia cells. In this report, to examine whether 8-NH 2 -Ado had the ability to enhance the radiation-induced cell killing in solid tumor cells, human lung adenocarcinoma A549 cells were irradiated in the presence and absence of 8-NH 2 -Ado. 8-NH 2 -Ado significantly increased reproductive cell death and apoptosis in A549 cells exposed to X-rays. When peptide inhibitors against caspase-3, -8, and -9 were utilized to evaluate the involvement of caspases, all inhibitors suppressed the enhancement of radiation-induced apoptosis, suggesting that not only mitochondria-mediated apoptotic signal transduction pathways but also death receptor-mediated pathways were involved in this enhancement of apoptosis. In addition, in the cells exposed to the treatment combining X-irradiation and 8-NH 2 -Ado, reduction of the intracellular ATP concentration was essential for survival, and down-regulation of the expression of antiapoptotic proteins such as survivin and X-linked inhibitor of apoptosis protein (XIAP) was observed. These results indicate that 8-NH 2 -Ado has potential not only as an anti-tumor drug for leukemia and lymphoma but also as a radiosensitizing agent for solid tumors. (author)

  9. Molecular improvement of alfalfa for enhanced productivity and adaptability in a changing environment.

    Science.gov (United States)

    Singer, Stacy D; Hannoufa, Abdelali; Acharya, Surya

    2017-10-18

    Due to an expanding world population and increased buying power, the demand for ruminant products such as meat and milk is expected to grow substantially in coming years, and high levels of forage crop production will therefore be a necessity. Unfortunately, urbanization of agricultural land, intensive agricultural practices, and climate change are all predicted to limit crop production in the future, which means that the development of forage cultivars with improved productivity and adaptability will be essential. Because alfalfa (Medicago sativa L.) is one of the most widely cultivated perennial forage crops, it has been the target of much research in this field. In this review, we discuss progress that has been made towards the improvement of productivity, abiotic stress tolerance, and nutrient-use efficiency, as well as disease and pest resistance, in alfalfa using biotechnological techniques. Furthermore, we consider possible future priorities and avenues for attaining further enhancements in this crop as a means of contributing to the realization of food security in a changing environment. © 2017 John Wiley & Sons Ltd.

  10. TGF-beta and 'adaptive' Foxp3(+) regulatory T cells.

    Science.gov (United States)

    Chen, Wanjun; Konkel, Joanne E

    2010-02-01

    In naïve T cells transforming growth factor-beta (TGF-beta) induces Foxp3, a transcription factor essential for programming and developing T regulatory cells (Treg cells). This finding reveals a physiological factor which can turn on the Foxp3 gene and establishes an experimental approach to induce antigen-specific Treg cells as a potential therapy for human diseases. While this role for TGF-beta is well confirmed, several critical questions remain largely unanswered and await further investigation. In this regard, it is imperative to understand the molecular pathways by which TGF-beta signaling initiates and regulates Foxp3 expression. It is also important to elucidate which factors and/or cytokines influence the TGF-beta-mediated conversion of naïve T cells and how to create an immunologically regulatory milieu to facilitate Treg cell generation in vivo. In this short article, we will highlight the key findings and recent progress in the field, discuss the molecular mechanisms underlying the TGF-beta-mediated induction of Foxp3, and attempt to outline the challenges ahead.

  11. Actin depolymerization enhances adipogenic differentiation in human stromal stem cells.

    Science.gov (United States)

    Chen, Li; Hu, Huimin; Qiu, Weimin; Shi, Kaikai; Kassem, Moustapha

    2018-05-01

    Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) or treating the cells by Phalloidin reduced adipocyte differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4). In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte differentiation depended on the activity of LIM domain kinase 1 (LIMK1) which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating hMSCs by Cytochalasin D inhibited ERK and Smad2 signaling and this was associated with enhanced adipocyte differentiation. On the other hand, Phalloidin enhanced ERK and Smad2 signaling, but inhibited adipocyte differentiation which was rescued by ERK specific chemical inhibitor U0126. Our data provide a link between restructuring of hMSCs cytoskeleton and hMSCs lineage commitment and differentiation. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. ARG1 Functions in the Physiological Adaptation of Undifferentiated Plant Cells to Spaceflight

    Science.gov (United States)

    Zupanska, Agata K.; Schultz, Eric R.; Yao, JiQiang; Sng, Natasha J.; Zhou, Mingqi; Callaham, Jordan B.; Ferl, Robert J.; Paul, Anna-Lisa

    2017-11-01

    Scientific access to spaceflight and especially the International Space Station has revealed that physiological adaptation to spaceflight is accompanied or enabled by changes in gene expression that significantly alter the transcriptome of cells in spaceflight. A wide range of experiments have shown that plant physiological adaptation to spaceflight involves gene expression changes that alter cell wall and other metabolisms. However, while transcriptome profiling aptly illuminates changes in gene expression that accompany spaceflight adaptation, mutation analysis is required to illuminate key elements required for that adaptation. Here we report how transcriptome profiling was used to gain insight into the spaceflight adaptation role of Altered response to gravity 1 (Arg1), a gene known to affect gravity responses in plants on Earth. The study compared expression profiles of cultured lines of Arabidopsis thaliana derived from wild-type (WT) cultivar Col-0 to profiles from a knock-out line deficient in the gene encoding ARG1 (ARG1 KO), both on the ground and in space. The cell lines were launched on SpaceX CRS-2 as part of the Cellular Expression Logic (CEL) experiment of the BRIC-17 spaceflight mission. The cultured cell lines were grown within 60 mm Petri plates in Petri Dish Fixation Units (PDFUs) that were housed within the Biological Research In Canisters (BRIC) hardware. Spaceflight samples were fixed on orbit. Differentially expressed genes were identified between the two environments (spaceflight and comparable ground controls) and the two genotypes (WT and ARG1 KO). Each genotype engaged unique genes during physiological adaptation to the spaceflight environment, with little overlap. Most of the genes altered in expression in spaceflight in WT cells were found to be Arg1-dependent, suggesting a major role for that gene in the physiological adaptation of undifferentiated cells to spaceflight.

  13. Enhancement of postreplication repair in Chinese hamster cells

    International Nuclear Information System (INIS)

    D'Ambrosio, S.M.; Setlow, R.B.

    1976-01-01

    Alkaline sedimentation profiles of pulse-labeled DNA from Chinese hamster cells showed that DNA from cells treated with N-acetoxy-acetylaminofluorene or ultraviolet radiation was made in segments smaller than those from untreated cells. Cells treated with a small dose (2.5 μM) of N-acetoxy-acetylaminofluorene or(2.5 J . m -2 ) 254-nm radiation, several hours before a larger dose (7 to 10 μM) of N-acetoxy-acetylaminofluorene or 5.0 J . m -2 of 254-nm radiation, also synthesized small DNA after the second dose. However, the rate at which this small DNA was joined together into parental size was appreciably greater than in absence of the small dose. This enhancement of postreplication repair (as a result of the initial small dose) was not observed when cells were incubated with cycloheximide between the two treatments. The results suggest that N-acetoxy-acetylaminofluorene and ultraviolet-damaged DNA from Chinese hamster cells are repaired by similar postreplicative mechanisms that require de novo protein synthesis for enhancement

  14. Modulatory Effects of Antibody Replacement Therapy to Innate and Adaptive Immune Cells

    Directory of Open Access Journals (Sweden)

    Isabella Quinti

    2017-06-01

    Full Text Available Intravenous immunoglobulin administered at replacement dosages modulates innate and adaptive immune cells in primary antibody deficiencies (PAD in a different manner to what observed when high dosages are used or when their effect is analyzed by in vitro experimental conditions. The effects seem to be beneficial on innate cells in that dendritic cells maturate, pro-inflammatory monocytes decrease, and neutrophil function is preserved. The effects are less clear on adaptive immune cells. IVIg induced a transient increase of Treg and a long-term increase of CD4 cells. More complex and less understood is the interplay of IVIg with defective B cells of PAD patients. The paucity of data underlies the need of more studies on patients with PAD before drawing conclusions on the in vivo mechanisms of action of IVIg based on in vitro investigations.

  15. Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy

    DEFF Research Database (Denmark)

    Nalla, Amarnadh; Ringholm, Lene; Søstrup, Birgitte

    2014-01-01

    is able to stimulate proliferation of rat beta cells. We have identified several circulating factors that may contribute to beta cell adaptation to pregnancy. Further studies are needed to elucidate their possible role in glucose homeostasis in the mother and her offspring.......OBJECTIVE: Several studies have shown an increase in beta cell mass during pregnancy. Somatolactogenic hormones are known to stimulate the proliferation of existing beta cells in rodents whereas the mechanism in humans is still unclear. We hypothesize that in addition to somatolactogenic hormones...... there are other circulating factors involved in beta cell adaptation to pregnancy. This study aimed at screening for potential pregnancy-associated circulating beta cell growth factors. SAMPLES: Serum samples from nonpregnant and pregnant women. METHODS: The effect of serum from pregnant women...

  16. Plasticity between Epithelial and Mesenchymal States Unlinks EMT from Metastasis-Enhancing Stem Cell Capacity

    Directory of Open Access Journals (Sweden)

    Evelyne Beerling

    2016-03-01

    Full Text Available Forced overexpression and/or downregulation of proteins regulating epithelial-to-mesenchymal transition (EMT has been reported to alter metastasis by changing migration and stem cell capacity of tumor cells. However, these manipulations artificially keep cells in fixed states, while in vivo cells may adapt transient and reversible states. Here, we have tested the existence and role of epithelial-mesenchymal plasticity in metastasis of mammary tumors without artificially modifying EMT regulators. In these tumors, we found by intravital microscopy that the motile tumor cells have undergone EMT, while their epithelial counterparts were not migratory. Moreover, we found that epithelial-mesenchymal plasticity renders any EMT-induced stemness differences, as reported previously, irrelevant for metastatic outgrowth, because mesenchymal cells that arrive at secondary sites convert to the epithelial state within one or two divisions, thereby obtaining the same stem cell potential as their arrived epithelial counterparts. We conclude that epithelial-mesenchymal plasticity supports migration but additionally eliminates stemness-enhanced metastatic outgrowth differences.

  17. Contact enhancement of locomotion in spreading cell colonies

    Science.gov (United States)

    D'Alessandro, Joseph; Solon, Alexandre P.; Hayakawa, Yoshinori; Anjard, Christophe; Detcheverry, François; Rieu, Jean-Paul; Rivière, Charlotte

    2017-10-01

    The dispersal of cells from an initially constrained location is a crucial aspect of many physiological phenomena, ranging from morphogenesis to tumour spreading. In such processes, cell-cell interactions may deeply alter the motion of single cells, and in turn the collective dynamics. While contact phenomena like contact inhibition of locomotion are known to come into play at high densities, here we focus on the little explored case of non-cohesive cells at moderate densities. We fully characterize the spreading of micropatterned colonies of Dictyostelium discoideum cells from the complete set of individual trajectories. From data analysis and simulation of an elementary model, we demonstrate that contact interactions act to speed up the early population spreading by promoting individual cells to a state of higher persistence, which constitutes an as-yet unreported contact enhancement of locomotion. Our findings also suggest that the current modelling paradigm of memoryless active particles may need to be extended to account for the history-dependent internal state of motile cells.

  18. Injectable biomimetic liquid crystalline scaffolds enhance muscle stem cell transplantation

    Science.gov (United States)

    Sleep, Eduard; McClendon, Mark T.; Preslar, Adam T.; Chen, Charlotte H.; Sangji, M. Hussain; Pérez, Charles M. Rubert; Haynes, Russell D.; Meade, Thomas J.; Blau, Helen M.; Stupp, Samuel I.

    2017-01-01

    Muscle stem cells are a potent cell population dedicated to efficacious skeletal muscle regeneration, but their therapeutic utility is currently limited by mode of delivery. We developed a cell delivery strategy based on a supramolecular liquid crystal formed by peptide amphiphiles (PAs) that encapsulates cells and growth factors within a muscle-like unidirectionally ordered environment of nanofibers. The stiffness of the PA scaffolds, dependent on amino acid sequence, was found to determine the macroscopic degree of cell alignment templated by the nanofibers in vitro. Furthermore, these PA scaffolds support myogenic progenitor cell survival and proliferation and they can be optimized to induce cell differentiation and maturation. We engineered an in vivo delivery system to assemble scaffolds by injection of a PA solution that enabled coalignment of scaffold nanofibers with endogenous myofibers. These scaffolds locally retained growth factors, displayed degradation rates matching the time course of muscle tissue regeneration, and markedly enhanced the engraftment of muscle stem cells in injured and noninjured muscles in mice. PMID:28874575

  19. Enhancing oral vaccine potency by targeting intestinal M cells.

    Directory of Open Access Journals (Sweden)

    Ali Azizi

    2010-11-01

    Full Text Available The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells.

  20. Changes in Purkinje cell simple spike encoding of reach kinematics during adaption to a mechanical perturbation.

    Science.gov (United States)

    Hewitt, Angela L; Popa, Laurentiu S; Ebner, Timothy J

    2015-01-21

    The cerebellum is essential in motor learning. At the cellular level, changes occur in both the simple spike and complex spike firing of Purkinje cells. Because simple spike discharge reflects the main output of the cerebellar cortex, changes in simple spike firing likely reflect the contribution of the cerebellum to the adapted behavior. Therefore, we investigated in Rhesus monkeys how the representation of arm kinematics in Purkinje cell simple spike discharge changed during adaptation to mechanical perturbations of reach movements. Monkeys rapidly adapted to a novel assistive or resistive perturbation along the direction of the reach. Adaptation consisted of matching the amplitude and timing of the perturbation to minimize its effect on the reach. In a majority of Purkinje cells, simple spike firing recorded before and during adaptation demonstrated significant changes in position, velocity, and acceleration sensitivity. The timing of the simple spike representations change within individual cells, including shifts in predictive versus feedback signals. At the population level, feedback-based encoding of position increases early in learning and velocity decreases. Both timing changes reverse later in learning. The complex spike discharge was only weakly modulated by the perturbations, demonstrating that the changes in simple spike firing can be independent of climbing fiber input. In summary, we observed extensive alterations in individual Purkinje cell encoding of reach kinematics, although the movements were nearly identical in the baseline and adapted states. Therefore, adaption to mechanical perturbation of a reaching movement is accompanied by widespread modifications in the simple spike encoding. Copyright © 2015 the authors 0270-6474/15/351106-19$15.00/0.

  1. Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy.

    Science.gov (United States)

    Ren, Jun; Gwin, William R; Zhou, Xinna; Wang, Xiaoli; Huang, Hongyan; Jiang, Ni; Zhou, Lei; Agarwal, Pankaj; Hobeika, Amy; Crosby, Erika; Hartman, Zachary C; Morse, Michael A; H Eng, Kevin; Lyerly, H Kim

    2017-01-01

    Purpose : Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy. Patients and Methods : We performed a pilot study of intratumoral HSV-GM-CSF OVT followed by autologous DC-CIK cell therapy. In addition to safety and clinical endpoints, we monitored adaptive T cell responses by quantifying T cell receptor (TCR) populations in pre-oncolytic therapy, post-oncolytic therapy, and after DC-CIK therapy. Results : Nine patients with advanced malignancy were treated with OVT (OrienX010), of whom seven experienced stable disease (SD). Five of the OVT treated patients underwent leukapheresis, generation, and delivery of DC-CIKs, and two had SD, whereas three progressed. T cell receptor sequencing of TCR β sequences one month after OVT therapy demonstrates a dynamic TCR repertoire in response to OVT therapy in the majority of patients with the systematic expansion of multiple T cell clone populations following DC-CIK therapy. This treatment was well tolerated and long-term event free and overall survival was observed in six of the nine patients. Conclusions : Strategies inducing the local activation of tumor-specific immune responses can be combined with adoptive cellular therapies to expand the adaptive T cell responses systemically and further studies are warranted.

  2. Child and parental adaptation to pediatric stem cell transplantation

    NARCIS (Netherlands)

    Vrijmoet-Wiersma, C. M. Jantien; Kolk, Annemarie M.; Grootenhuis, Martha A.; Spek, Emmelien M.; van Klink, Jeanine M. M.; Egeler, R. Maarten; Bredius, Robbert G. M.; Koopman, Hendrik M.

    2009-01-01

    Allogeneic pediatric stem cell transplantation (SCT) is a very intensive treatment with a high mortality and morbidity. The objectives of this study were to assess the (1) self- and proxy-reported health-related quality of life (HRQoL) compared to a norm group, (2) levels of parenting stress

  3. Child and parental adaptation to pediatric stem cell transplantation

    NARCIS (Netherlands)

    Vrijmoet-Wiersma, C.M.J.; Kolk, A.M.; Grootenhuis, M.A.; Spek, E.M.; van Klink, J.M.M.; Egeler, R.M.; Bredius, R.G.M.; Koopman, H.M.

    2009-01-01

    Goals of work: Allogeneic pediatric stem cell transplantation (SCT) is a very intensive treatment with a high mortality and morbidity. The objectives of this study were to assess the (1) self- and proxy-reported health-related quality of life (HRQoL) compared to a norm group, (2) levels of parenting

  4. Flexible organic solar cells including efficiency enhancing grating structures

    International Nuclear Information System (INIS)

    De Oliveira Hansen, Roana Melina; Liu Yinghui; Madsen, Morten; Rubahn, Horst-Günter

    2013-01-01

    In this work, a new method for the fabrication of organic solar cells containing functional light-trapping nanostructures on flexible substrates is presented. Polyimide is spin-coated on silicon support substrates, enabling standard micro- and nanotechnology fabrication techniques, such as photolithography and electron-beam lithography, besides the steps required for the bulk-heterojunction organic solar cell fabrication. After the production steps, the solar cells on polyimide are peeled off the silicon support substrates, resulting in flexible devices containing nanostructures for light absorption enhancement. Since the solar cells avoid using brittle electrodes, the performance of the flexible devices is not affected by the peeling process. We have investigated three different nanostructured grating designs and conclude that gratings with a 500 nm pitch distance have the highest light-trapping efficiency for the selected active layer material (P3HT:PCBM), resulting in an enhancement of about 34% on the solar cell efficiency. The presented method can be applied to a large variety of flexible nanostructured devices in future applications. (paper)

  5. HES6 enhances the motility of alveolar rhabdomyosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wickramasinghe, Caroline M [MRC Cancer Cell Unit, Hutchison-MRC Research centre, Addenbrooke' s Hospital Cambridge, CB2 0XZ (United Kingdom); MRC Laboratory of Molecular Biology, Addenbrooke' s Hospital Cambridge, CB2 0QH (United Kingdom); Domaschenz, Renae [MRC Cancer Cell Unit, Hutchison-MRC Research centre, Addenbrooke' s Hospital Cambridge, CB2 0XZ (United Kingdom); Gene Regulation and Chromatin Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 ONN (United Kingdom); Amagase, Yoko [MRC Cancer Cell Unit, Hutchison-MRC Research centre, Addenbrooke' s Hospital Cambridge, CB2 0XZ (United Kingdom); Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women' s College of Liberal Arts, Kodo, Kyotanabe, Kyoto 610-0395 (Japan); Williamson, Daniel [Molecular Cytogenetics, The Institute of Cancer Research, Sutton SM2 5NG (United Kingdom); Northern Institute for Cancer Research, Paul O' Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH (United Kingdom); Missiaglia, Edoardo; Shipley, Janet [Molecular Cytogenetics, The Institute of Cancer Research, Sutton SM2 5NG (United Kingdom); Murai, Kasumi [MRC Cancer Cell Unit, Hutchison-MRC Research centre, Addenbrooke' s Hospital Cambridge, CB2 0XZ (United Kingdom); Jones, Philip H, E-mail: phj20@cam.ac.uk [MRC Cancer Cell Unit, Hutchison-MRC Research centre, Addenbrooke' s Hospital Cambridge, CB2 0XZ (United Kingdom)

    2013-01-01

    Absract: HES6, a member of the hairy-enhancer-of-split family of transcription factors, plays multiple roles in myogenesis. It is a direct target of the myogenic transcription factor MyoD and has been shown to regulate the formation of the myotome in development, myoblast cell cycle exit and the organization of the actin cytoskeleton during terminal differentiation. Here we investigate the expression and function of HES6 in rhabdomyosarcoma, a soft tissue tumor which expresses myogenic genes but fails to differentiate into muscle. We show that HES6 is expressed at high levels in the subset of alveolar rhabdomyosarcomas expressing PAX/FOXO1 fusion genes (ARMSp). Knockdown of HES6 mRNA in the ARMSp cell line RH30 reduces proliferation and cell motility. This phenotype is rescued by expression of mouse Hes6 which is insensitive to HES6 siRNA. Furthermore, expression microarray analysis indicates that the HES6 knockdown is associated with a decrease in the levels of Transgelin, (TAGLN), a regulator of the actin cytoskeleton. Knockdown of TAGLN decreases cell motility, whilst TAGLN overexpression rescues the motility defect resulting from HES6 knockdown. These findings indicate HES6 contributes to the pathogenesis of ARMSp by enhancing both proliferation and cell motility.

  6. Enzymes and other agents that enhance cell wall extensibility

    Science.gov (United States)

    Cosgrove, D. J.

    1999-01-01

    Polysaccharides and proteins are secreted to the inner surface of the growing cell wall, where they assemble into a network that is mechanically strong, yet remains extensible until the cells cease growth. This review focuses on the agents that directly or indirectly enhance the extensibility properties of growing walls. The properties of expansins, endoglucanases, and xyloglucan transglycosylases are reviewed and their postulated roles in modulating wall extensibility are evaluated. A summary model for wall extension is presented, in which expansin is a primary agent of wall extension, whereas endoglucanases, xyloglucan endotransglycosylase, and other enzymes that alter wall structure act secondarily to modulate expansin action.

  7. Delayed rectifier K channels contribute to contrast adaptation in mammalian retinal ganglion cells

    Science.gov (United States)

    Weick, Michael; Demb, Jonathan B.

    2011-01-01

    SUMMARY Retinal ganglion cells adapt by reducing their sensitivity during periods of high contrast. Contrast adaptation in the firing response depends on both presynaptic and intrinsic mechanisms. Here, we investigated intrinsic mechanisms for contrast adaptation in OFF Alpha ganglion cells in the in vitro guinea pig retina. Using either visual stimulation or current injection, we show that brief depolarization evoked spiking and suppressed firing during subsequent depolarization. The suppression could be explained by Na channel inactivation, as shown in salamander cells. However, brief hyperpolarization in the physiological range (5–10 mV) also suppressed firing during subsequent depolarization. This suppression was sensitive selectively to blockers of delayed-rectifier K channels (KDR). Somatic membrane patches showed TEA-sensitive KDR currents with activation near −25 mV and removal of inactivation at voltages negative to Vrest. Brief periods of hyperpolarization apparently remove KDR inactivation and thereby increase the channel pool available to suppress excitability during subsequent depolarization. PMID:21745646

  8. Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

    DEFF Research Database (Denmark)

    Chen, Li; Hu, Huimin; Qiu, Weimin

    2018-01-01

    Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined...... differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4). In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte...... differentiation depended on the activity of LIM domain kinase 1 (LIMK1) which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating h...

  9. Adaptability and variability of the cell functions to the environmental factors

    Energy Technology Data Exchange (ETDEWEB)

    Kikuchi, Tadatoshi [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.

    1995-02-01

    Adaptive phenomenon of the cells to the environmental factors is one of the most important functions of cells. In the initial research program, yeast, Saccharomyces cerevisiae, as model species of eukaryote was selected to use for the experiments and copper sulfate was adopted as one of the ideal environmental factors, and then adaptation mechanisms of yeast cells in the environment surrounded by copper ions were analyzed metabolically and morphologically. Furthermore, in the relationships between environmental factors and the cells, the researches performed were as follows: (1) Induced mutation in the extranuclear-inheritable system: Mutagenic effect of ethidium bromide on mitochondria and plastids. (2) Induction of gene expression by light exposure in the early development of chloroplast in Chlamydomonas reinhardi. (3) Some features of RNA and protein syntheses in thermophilic alga Cyanidium caldarium. (4) Satellite DNA of Ochromonas danica. (5) Analyses of cell functions using various kinds of radiations. (6) Novel methionine requirement of radiation resistant bacterium, Deinococcus radiodurans. (author).

  10. Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

    Directory of Open Access Journals (Sweden)

    Li Chen

    2018-05-01

    Full Text Available Human stromal stem cells (hMSCs differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs: Cofilin 1 (CFL1 and Destrin (DSTN or treating the cells by Phalloidin reduced adipocyte differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4. In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte differentiation depended on the activity of LIM domain kinase 1 (LIMK1 which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating hMSCs by Cytochalasin D inhibited ERK and Smad2 signaling and this was associated with enhanced adipocyte differentiation. On the other hand, Phalloidin enhanced ERK and Smad2 signaling, but inhibited adipocyte differentiation which was rescued by ERK specific chemical inhibitor U0126. Our data provide a link between restructuring of hMSCs cytoskeleton and hMSCs lineage commitment and differentiation. Keywords: Actin cytoskeleton, Actin depolymerizing factors, Adipocyte differentiation, Human stromal stem cells

  11. Interfacial Layer Engineering for Performance Enhancement in Polymer Solar Cells

    Directory of Open Access Journals (Sweden)

    Hao Zeng

    2015-02-01

    Full Text Available Improving power conversion efficiency and device performance stability is the most critical challenge in polymer solar cells for fulfilling their applications in industry at large scale. Various methodologies have been developed for realizing this goal, among them interfacial layer engineering has shown great success, which can optimize the electrical contacts between active layers and electrodes and lead to enhanced charge transport and collection. Interfacial layers also show profound impacts on light absorption and optical distribution of solar irradiation in the active layer and film morphology of the subsequently deposited active layer due to the accompanied surface energy change. Interfacial layer engineering enables the use of high work function metal electrodes without sacrificing device performance, which in combination with the favored kinetic barriers against water and oxygen penetration leads to polymer solar cells with enhanced performance stability. This review provides an overview of the recent progress of different types of interfacial layer materials, including polymers, small molecules, graphene oxides, fullerene derivatives, and metal oxides. Device performance enhancement of the resulting solar cells will be elucidated and the function and operation mechanism of the interfacial layers will be discussed.

  12. Enhanced cognitive behavioral therapy for eating disorders adapted for a group setting.

    Science.gov (United States)

    Wade, Stephanie; Byrne, Sue; Allen, Karina

    2017-08-01

    This randomized control trial is an evaluation of the effectiveness of enhanced cognitive behavioral treatment (CBT-E) for eating disorders adapted for a group setting. The study aimed to examine the effects of group CBT-E on eating disorder psychopathology and additional maintaining pathology. A transdiagnostic sample of individuals with eating disorders with a BMI ≥ 18 kg/m 2 (N = 40) were randomized to an immediate-start or delayed-start condition so as to compare therapeutic effects of group CBT-E with a waitlist control. Global Eating Disorder Examination Questionnaire (EDE-Q) scores, BMI, and measures of Clinical Perfectionism, Self-Esteem, Interpersonal Difficulties, and Mood Intolerance were measured across the 8-week control period, throughout the group treatment and at 3-months post-treatment. Over 70% of those who entered the trial completed treatment. The first eight weeks of group CBT-E were more effective at reducing Global EDE-Q scores than no treatment (waitlist control). By post-treatment, good outcome (a Global EDE-Q within 1 SD of Australian community norms plus BMI ≥ 18.5) was achieved by 67.9% of treatment completers and 66.7% of the total sample. Symptom abstinence within the previous month was reported by 14.3% of treatment completers and 10.3% of the total sample. Significant reductions in Clinical Perfectionism, Self-Esteem, Interpersonal Difficulties, and Mood Intolerance were also observed. This study demonstrated that a group version of CBT-E can be effective at reducing eating disorder psychopathology in a transdiagnostic sample of individuals with eating disorders. Group CBT-E could provide a means of increasing availability of evidence-based treatment for eating disorders. © 2017 Wiley Periodicals, Inc.

  13. Prostate segmentation by feature enhancement using domain knowledge and adaptive region based operations

    International Nuclear Information System (INIS)

    Nanayakkara, Nuwan D; Samarabandu, Jagath; Fenster, Aaron

    2006-01-01

    Estimation of prostate location and volume is essential in determining a dose plan for ultrasound-guided brachytherapy, a common prostate cancer treatment. However, manual segmentation is difficult, time consuming and prone to variability. In this paper, we present a semi-automatic discrete dynamic contour (DDC) model based image segmentation algorithm, which effectively combines a multi-resolution model refinement procedure together with the domain knowledge of the image class. The segmentation begins on a low-resolution image by defining a closed DDC model by the user. This contour model is then deformed progressively towards higher resolution images. We use a combination of a domain knowledge based fuzzy inference system (FIS) and a set of adaptive region based operators to enhance the edges of interest and to govern the model refinement using a DDC model. The automatic vertex relocation process, embedded into the algorithm, relocates deviated contour points back onto the actual prostate boundary, eliminating the need of user interaction after initialization. The accuracy of the prostate boundary produced by the proposed algorithm was evaluated by comparing it with a manually outlined contour by an expert observer. We used this algorithm to segment the prostate boundary in 114 2D transrectal ultrasound (TRUS) images of six patients scheduled for brachytherapy. The mean distance between the contours produced by the proposed algorithm and the manual outlines was 2.70 ± 0.51 pixels (0.54 ± 0.10 mm). We also showed that the algorithm is insensitive to variations of the initial model and parameter values, thus increasing the accuracy and reproducibility of the resulting boundaries in the presence of noise and artefacts

  14. Host cell reactivation and UV-enhanced reactivation in synchronized mammalian cells

    International Nuclear Information System (INIS)

    Lytle, C.D.; Schmidt, B.J.

    1981-01-01

    Does host cell reactivation (HCR) or UV-enhanced reactivation (UVER) of UV-irradiated Herpes simplex virus (UV-HSV) vary during the host mammalian cell cycle. The answer could be useful for interpreting UVER and or the two-component nature of the UV-HSV survival curve. Procedures were developed for infection of mitotically-synchronized CV-l monkey kidney cells. All virus survival curves determined at different cell cycle stages had two components with similar D 0 's and intercepts of the second components. Thus, no single stage of the host cell cycle was responsible for the second component of the virus survival curve. When the cells were UV-irradiated immediately prior to infection, enhanced survival of UV-HSV occurred for cell irradiation and virus infection initiated during late G 1 early S phase or late S early G 2 phase but not during early G 1 phase. For infection delayed by 24 h after cell irradiation, UVER was found at all investigated times. These results indicate that: (1) HCR is similar at all stages of the host cell cycle: and (2) the ''induction'' of UVER is not as rapid for cell-irradiation in early G 1 phase. This latter observation may be one reason why normal, contact-inhibited cells do not express UVER as rapidly as faster growing, less contact-inhibited cells. (author)

  15. Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells

    International Nuclear Information System (INIS)

    Nakajima, Hideaki; Shibata, Fumi; Fukuchi, Yumi; Goto-Koshino, Yuko; Ito, Miyuki; Urano, Atsushi; Nakahata, Tatsutoshi; Aburatani, Hiroyuki; Kitamura, Toshio

    2006-01-01

    Immune suppressor factor (ISF) is a subunit of the vacuolar ATPase proton pump. We earlier identified a short form of ISF (ShIF) as a stroma-derived factor that supports cytokine-independent growth of mutant Ba/F3 cells. Here, we report that ISF/ShIF supports self-renewal and expansion of primary hematopoietic stem cells (HSCs). Co-culture of murine bone marrow cells with a stromal cell line overexpressing ISF or ShIF (MS10/ISF or MS10/ShIF) not only enhanced their colony-forming activity and the numbers of long-term culture initiating cells, but also maintained the competitive repopulating activity of HSC. This stem cell supporting activity depended on the proton-transfer function of ISF/ShIF. Gene expression analysis of ISF/ShIF-transfected cell lines revealed down-regulation of secreted frizzled-related protein-1 and tissue inhibitor of metalloproteinase-3, and the restoration of their expressions in MS10/ISF cells partially reversed its enhanced LTC-IC supporting activity to a normal level. These results suggest that ISF/ShIF confers stromal cells with enhanced supporting activities for HSCs by modulating Wnt-activity and the extracellular matrix

  16. Persistence and Adaptation in Immunity: T Cells Balance the Extent and Thoroughness of Search.

    Directory of Open Access Journals (Sweden)

    G Matthew Fricke

    2016-03-01

    Full Text Available Effective search strategies have evolved in many biological systems, including the immune system. T cells are key effectors of the immune response, required for clearance of pathogenic infection. T cell activation requires that T cells encounter antigen-bearing dendritic cells within lymph nodes, thus, T cell search patterns within lymph nodes may be a crucial determinant of how quickly a T cell immune response can be initiated. Previous work suggests that T cell motion in the lymph node is similar to a Brownian random walk, however, no detailed analysis has definitively shown whether T cell movement is consistent with Brownian motion. Here, we provide a precise description of T cell motility in lymph nodes and a computational model that demonstrates how motility impacts T cell search efficiency. We find that both Brownian and Lévy walks fail to capture the complexity of T cell motion. Instead, T cell movement is better described as a correlated random walk with a heavy-tailed distribution of step lengths. Using computer simulations, we identify three distinct factors that contribute to increasing T cell search efficiency: 1 a lognormal distribution of step lengths, 2 motion that is directionally persistent over short time scales, and 3 heterogeneity in movement patterns. Furthermore, we show that T cells move differently in specific frequently visited locations that we call "hotspots" within lymph nodes, suggesting that T cells change their movement in response to the lymph node environment. Our results show that like foraging animals, T cells adapt to environmental cues, suggesting that adaption is a fundamental feature of biological search.

  17. Persistence and Adaptation in Immunity: T Cells Balance the Extent and Thoroughness of Search

    Science.gov (United States)

    Fricke, G. Matthew; Letendre, Kenneth A.; Moses, Melanie E.; Cannon, Judy L.

    2016-01-01

    Effective search strategies have evolved in many biological systems, including the immune system. T cells are key effectors of the immune response, required for clearance of pathogenic infection. T cell activation requires that T cells encounter antigen-bearing dendritic cells within lymph nodes, thus, T cell search patterns within lymph nodes may be a crucial determinant of how quickly a T cell immune response can be initiated. Previous work suggests that T cell motion in the lymph node is similar to a Brownian random walk, however, no detailed analysis has definitively shown whether T cell movement is consistent with Brownian motion. Here, we provide a precise description of T cell motility in lymph nodes and a computational model that demonstrates how motility impacts T cell search efficiency. We find that both Brownian and Lévy walks fail to capture the complexity of T cell motion. Instead, T cell movement is better described as a correlated random walk with a heavy-tailed distribution of step lengths. Using computer simulations, we identify three distinct factors that contribute to increasing T cell search efficiency: 1) a lognormal distribution of step lengths, 2) motion that is directionally persistent over short time scales, and 3) heterogeneity in movement patterns. Furthermore, we show that T cells move differently in specific frequently visited locations that we call “hotspots” within lymph nodes, suggesting that T cells change their movement in response to the lymph node environment. Our results show that like foraging animals, T cells adapt to environmental cues, suggesting that adaption is a fundamental feature of biological search. PMID:26990103

  18. Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress.

    Science.gov (United States)

    Glorieux, Christophe; Sandoval, Juan Marcelo; Fattaccioli, Antoine; Dejeans, Nicolas; Garbe, James C; Dieu, Marc; Verrax, Julien; Renard, Patricia; Huang, Peng; Calderon, Pedro Buc

    2016-10-01

    Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in cancer cells, but the molecular mechanism that regulates catalase, a key antioxidant enzyme responsible for conversion of hydrogen peroxide to water and oxygen, remains to be elucidated. Therefore, we investigated the transcriptional regulatory mechanism controlling catalase expression in three human mammary cell lines: the normal mammary epithelial 250MK primary cells, the breast adenocarcinoma MCF-7 cells and an experimental model of MCF-7 cells resistant against oxidative stress resulting from chronic exposure to H 2 O 2 (Resox), in which catalase was overexpressed. Here we identify a novel promoter region responsible for the regulation of catalase expression at -1518/-1226 locus and the key molecules that interact with this promoter and affect catalase transcription. We show that the AP-1 family member JunB and retinoic acid receptor alpha (RARα) mediate catalase transcriptional activation and repression, respectively, by controlling chromatin remodeling through a histone deacetylases-dependent mechanism. This regulatory mechanism plays an important role in redox adaptation to chronic exposure to H 2 O 2 in breast cancer cells. Our study suggests that cancer adaptation to oxidative stress may be regulated by transcriptional factors through chromatin remodeling, and reveals a potential new mechanism to target cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Bee venom enhances the differentiation of human regulatory T cells.

    Science.gov (United States)

    Caramalho, I; Melo, A; Pedro, E; Barbosa, M M P; Victorino, R M M; Pereira Santos, M C; Sousa, A E

    2015-10-01

    Venom-specific immunotherapy (VIT) is well recognized by its efficacy, and compelling evidence implicates regulatory T cells (Tregs) in the underlying tolerogenic mechanisms. Additionally, hymenoptera venom has for a long time been claimed to modulate immunity. Here, we investigated the putative role of bee venom (Bv) in human FOXP3-expressing Treg homeostasis and differentiation, irrespective of the donors' allergic status. We found that Bv significantly enhanced the differentiation of FOXP3-expressing cells both from conventional naïve CD4 T cells and mature CD4 thymocytes, a property that may contribute to the VIT's capacity to expand circulating Tregs in allergic individuals. We expect that our data enlightening the Treg-mediated immunomodulatory properties of Bv regardless of TCR specificity, to have application in other allergies, as well as in other clinical settings, such as autoimmunity and transplantation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

    Science.gov (United States)

    Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

    2016-06-01

    Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

  1. Enhancing adaptive sparse grid approximations and improving refinement strategies using adjoint-based a posteriori error estimates

    Science.gov (United States)

    Jakeman, J. D.; Wildey, T.

    2015-01-01

    In this paper we present an algorithm for adaptive sparse grid approximations of quantities of interest computed from discretized partial differential equations. We use adjoint-based a posteriori error estimates of the physical discretization error and the interpolation error in the sparse grid to enhance the sparse grid approximation and to drive adaptivity of the sparse grid. Utilizing these error estimates provides significantly more accurate functional values for random samples of the sparse grid approximation. We also demonstrate that alternative refinement strategies based upon a posteriori error estimates can lead to further increases in accuracy in the approximation over traditional hierarchical surplus based strategies. Throughout this paper we also provide and test a framework for balancing the physical discretization error with the stochastic interpolation error of the enhanced sparse grid approximation.

  2. Enhancing adaptive sparse grid approximations and improving refinement strategies using adjoint-based a posteriori error estimates

    International Nuclear Information System (INIS)

    Jakeman, J.D.; Wildey, T.

    2015-01-01

    In this paper we present an algorithm for adaptive sparse grid approximations of quantities of interest computed from discretized partial differential equations. We use adjoint-based a posteriori error estimates of the physical discretization error and the interpolation error in the sparse grid to enhance the sparse grid approximation and to drive adaptivity of the sparse grid. Utilizing these error estimates provides significantly more accurate functional values for random samples of the sparse grid approximation. We also demonstrate that alternative refinement strategies based upon a posteriori error estimates can lead to further increases in accuracy in the approximation over traditional hierarchical surplus based strategies. Throughout this paper we also provide and test a framework for balancing the physical discretization error with the stochastic interpolation error of the enhanced sparse grid approximation

  3. Mesenchymal stem cells enhance the metastasis of 3D-cultured hepatocellular carcinoma cells

    International Nuclear Information System (INIS)

    Liu, Chang; Liu, Yang; Xu, Xiao-xi; Guo, Xin; Sun, Guang-wei; Ma, Xiao-jun

    2016-01-01

    Accumulating evidences have demonstrated that mesenchymal stem cells (MSC) could be recruited to the tumor microenvironment. Umbilical cord mesenchymal stem cells (UCMSC) were attractive vehicles for delivering therapeutic agents against cancer. Nevertheless, the safety of UCMSC in the treatment of tumors including hepatocellular carcinoma (HCC) was still undetermined. In this study, an in vitro co-culture system was established to evaluate the effect of UCMSC on the cell growth, cancer stem cell (CSC) characteristics, drug resistance, metastasis of 3D-cultured HCC cells, and the underlying mechanism was also investigated. It was found that after co-cultured with UCMSC, the metastatic ability of 3D-cultured HCC cells was significantly enhanced as indicated by up-regulation of matrix metalloproteinase (MMP), epithelial-mesenchymal transition (EMT)-related genes, and migration ability. However, cell growth, drug resistance and CSC-related gene expression of HCC cells were not affected by UCMSC. Moreover, EMT was reversed, MMP-2 expression was down-regulated, and migration ability of HCC cell was significantly inhibited when TGF-β receptor inhibitor SB431542 was added into the co-culture system. Therefore, these data indicated that UCMSC could significantly enhance the tumor cell metastasis, which was due to the EMT of HCC cells induced by TGF-β. The online version of this article (doi:10.1186/s12885-016-2595-4) contains supplementary material, which is available to authorized users

  4. Adaptation of red cell enzymes and intermediates in metabolic disorders.

    Science.gov (United States)

    Goebel, K M; Goebel, F D; Neitzert, A; Hausmann, L; Schneider, J

    1975-01-01

    The metabolic activity of the red cell glycolytic pathway hexose monophosphate shunt (HMP) with dependent glutathione system was studied in patients with hyperthyroidism (n = 10), hyperlipoproteinemia (n = 16), hypoglycemia (n = 25) and hyperglycemia (n = 23). In uncontrolled diabetics and patients with hyperthyroidism the mean value of glucose phosphate isomerase (GPI), glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GR) was increased, whereas these enzyme activities were reduced in patients with hypoglycemia. Apart from a few values of hexokinase (HK) which were lower than normal the results in hyperlipoproteinemia patients remained essentially unchanged, including the intermediates such as 2,3-diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP) and reduced glutathione (GSH). While increased rates of 2,3-DPG and ATP in hypoglycemia patients were obtained, these substrates were markedly reduced in diabetics.

  5. Adaptive Mutations in Influenza A/California/07/2009 Enhance Polymerase Activity and Infectious Virion Production

    Science.gov (United States)

    Slaine, Patrick D.; MacRae, Cara; Kleer, Mariel; Lamoureux, Emily; McAlpine, Sarah; Warhuus, Michelle; Comeau, André M.; Hatchette, Todd

    2018-01-01

    Mice are not natural hosts for influenza A viruses (IAVs), but they are useful models for studying antiviral immune responses and pathogenesis. Serial passage of IAV in mice invariably causes the emergence of adaptive mutations and increased virulence. Here, we report the adaptation of IAV reference strain A/California/07/2009(H1N1) (also known as CA/07) in outbred Swiss Webster mice. Serial passage led to increased virulence and lung titers, and dissemination of the virus to brains. We adapted a deep-sequencing protocol to identify and enumerate adaptive mutations across all genome segments. Among mutations that emerged during mouse-adaptation, we focused on amino acid substitutions in polymerase subunits: polymerase basic-1 (PB1) T156A and F740L and polymerase acidic (PA) E349G. These mutations were evaluated singly and in combination in minigenome replicon assays, which revealed that PA E349G increased polymerase activity. By selectively engineering three PB1 and PA mutations into the parental CA/07 strain, we demonstrated that these mutations in polymerase subunits decreased the production of defective viral genome segments with internal deletions and dramatically increased the release of infectious virions from mouse cells. Together, these findings increase our understanding of the contribution of polymerase subunits to successful host adaptation. PMID:29783694

  6. Assessing and Exploiting Functional Diversity in Germplasm Pools to Enhance Abiotic Stress Adaptation and Yield in Cereals and Food Legumes

    Science.gov (United States)

    Dwivedi, Sangam L.; Scheben, Armin; Edwards, David; Spillane, Charles; Ortiz, Rodomiro

    2017-01-01

    There is a need to accelerate crop improvement by introducing alleles conferring host plant resistance, abiotic stress adaptation, and high yield potential. Elite cultivars, landraces and wild relatives harbor useful genetic variation that needs to be more easily utilized in plant breeding. We review genome-wide approaches for assessing and identifying alleles associated with desirable agronomic traits in diverse germplasm pools of cereals and legumes. Major quantitative trait loci and single nucleotide polymorphisms (SNPs) associated with desirable agronomic traits have been deployed to enhance crop productivity and resilience. These include alleles associated with variation conferring enhanced photoperiod and flowering traits. Genetic variants in the florigen pathway can provide both environmental flexibility and improved yields. SNPs associated with length of growing season and tolerance to abiotic stresses (precipitation, high temperature) are valuable resources for accelerating breeding for drought-prone environments. Both genomic selection and genome editing can also harness allelic diversity and increase productivity by improving multiple traits, including phenology, plant architecture, yield potential and adaptation to abiotic stresses. Discovering rare alleles and useful haplotypes also provides opportunities to enhance abiotic stress adaptation, while epigenetic variation has potential to enhance abiotic stress adaptation and productivity in crops. By reviewing current knowledge on specific traits and their genetic basis, we highlight recent developments in the understanding of crop functional diversity and identify potential candidate genes for future use. The storage and integration of genetic, genomic and phenotypic information will play an important role in ensuring broad and rapid application of novel genetic discoveries by the plant breeding community. Exploiting alleles for yield-related traits would allow improvement of selection efficiency and

  7. Assessing and Exploiting Functional Diversity in Germplasm Pools to Enhance Abiotic Stress Adaptation and Yield in Cereals and Food Legumes

    Directory of Open Access Journals (Sweden)

    Sangam L. Dwivedi

    2017-08-01

    Full Text Available There is a need to accelerate crop improvement by introducing alleles conferring host plant resistance, abiotic stress adaptation, and high yield potential. Elite cultivars, landraces and wild relatives harbor useful genetic variation that needs to be more easily utilized in plant breeding. We review genome-wide approaches for assessing and identifying alleles associated with desirable agronomic traits in diverse germplasm pools of cereals and legumes. Major quantitative trait loci and single nucleotide polymorphisms (SNPs associated with desirable agronomic traits have been deployed to enhance crop productivity and resilience. These include alleles associated with variation conferring enhanced photoperiod and flowering traits. Genetic variants in the florigen pathway can provide both environmental flexibility and improved yields. SNPs associated with length of growing season and tolerance to abiotic stresses (precipitation, high temperature are valuable resources for accelerating breeding for drought-prone environments. Both genomic selection and genome editing can also harness allelic diversity and increase productivity by improving multiple traits, including phenology, plant architecture, yield potential and adaptation to abiotic stresses. Discovering rare alleles and useful haplotypes also provides opportunities to enhance abiotic stress adaptation, while epigenetic variation has potential to enhance abiotic stress adaptation and productivity in crops. By reviewing current knowledge on specific traits and their genetic basis, we highlight recent developments in the understanding of crop functional diversity and identify potential candidate genes for future use. The storage and integration of genetic, genomic and phenotypic information will play an important role in ensuring broad and rapid application of novel genetic discoveries by the plant breeding community. Exploiting alleles for yield-related traits would allow improvement of selection

  8. Induction of quiescence (G0) in bone marrow stromal stem cells enhances their stem cell characteristics

    DEFF Research Database (Denmark)

    Rumman, Mohammad; Majumder, Abhijit; Harkness, Linda

    2018-01-01

    Several studies have suggested that bone marrow stromal steam cells (BMSC) exist in a quiescent state (G0) within the in vivo niche; however, an explicit analysis of the biology of G0 state-BMSC has not been reported. We hypothesized that induction of G0 in BMSC might enhance their stem cell...... properties. Thus, we induced quiescence in BMSC in vitro by (a) suspension culture in a viscous medium or (b) culture on soft polyacrylamide substrate; and examined their molecular and functional phenotype. Induction of G0 was confirmed by bromo-deoxyuridine (BrdU) labelling and analysis of cell cycle gene...... expression. Upon reactivation and re-entry into cell cycle, G0 state-BMSC exhibited enhanced clonogenic self-renewal, preferential differentiation into osteoblastic rather than adipocytic cells and increased ectopic bone formation when implanted subcutaneously in vivo in immune-deficient mice, compared...

  9. Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells

    International Nuclear Information System (INIS)

    Wörmann, Xenia; Lesch, Markus; Welke, Robert-William; Okonechnikov, Konstantin; Abdurishid, Mirshat; Sieben, Christian; Geissner, Andreas; Brinkmann, Volker; Kastner, Markus; Karner, Andreas; Zhu, Rong; Hinterdorfer, Peter; Anish, Chakkumkal; Seeberger, Peter H.; Herrmann, Andreas

    2016-01-01

    The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA_1 D130E, HA_2 I91L), near the receptor binding site and the stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production. - Highlights: • We observed a spontaneous mutation of a 2009-pandemic H1N1 influenza virus in vitro. • The adaptation led to a 100-fold rise in replication rate in human A549 cells. • Adaptation was caused by two mutations in the HA gene segment. • Adaptation correlates with increased fusion pH and decreased receptor affinity.

  10. Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wörmann, Xenia [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Lesch, Markus [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Steinbeis Innovation gGmbH, Center for Systems Biomedicine, Falkensee (Germany); Welke, Robert-William [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Okonechnikov, Konstantin; Abdurishid, Mirshat [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Sieben, Christian [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Geissner, Andreas [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Brinkmann, Volker [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Kastner, Markus [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Karner, Andreas [Center for Advanced Bioanalysis GmbH (CBL), Linz (Austria); Zhu, Rong; Hinterdorfer, Peter [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Anish, Chakkumkal [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Seeberger, Peter H. [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Herrmann, Andreas [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); and others

    2016-05-15

    The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA{sub 1} D130E, HA{sub 2} I91L), near the receptor binding site and the stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production. - Highlights: • We observed a spontaneous mutation of a 2009-pandemic H1N1 influenza virus in vitro. • The adaptation led to a 100-fold rise in replication rate in human A549 cells. • Adaptation was caused by two mutations in the HA gene segment. • Adaptation correlates with increased fusion pH and decreased receptor affinity.

  11. The effects of country-level population policy for enhancing adaptation to climate change

    Science.gov (United States)

    Gunasekara, N. K.; Kazama, S.; Yamazaki, D.; Oki, T.

    2013-11-01

    -stressed regions is almost 20 times lower than that in the lower latitudes. For countries with high population momentum, the population policy scenario with fertility-reduction assumptions gained a maximum of 6.1 times the water availability in Niger and 5.3 times that in Uganda compared with the no-policy scenario. Most of these countries are in sub-Saharan Africa. These countries represent 24.5% of the global population in the no-policy scenario, and the scenario with fertility-reduction assumptions reduces it to 8.7% by 2100. This scenario is also effective in reducing the area under extreme water stress in these countries. However, the policy scenario with assumptions of population stabilization at the replacement fertility rate increases the water stress in high-latitude countries. Nevertheless, the impact is low due to the high per capita water availability in the region. This research is expected to widen the understanding of the combined impacts of climate change in the future and of the strategies needed to enhance the space for adaptation.

  12. Emerging roles of extracellular vesicles in the adaptive response of tumour cells to microenvironmental stress

    Directory of Open Access Journals (Sweden)

    Paulina Kucharzewska

    2013-03-01

    Full Text Available Cells are constantly subjected to various types of endogenous and exogenous stressful stimuli, which can cause serious and even permanent damage. The ability of a cell to sense and adapt to environmental alterations is thus vital to maintain tissue homeostasis during development and adult life. Here, we review some of the major phenotypic characteristics of the hostile tumour microenvironment and the emerging roles of extracellular vesicles in these events.

  13. Small molecules enhance CRISPR genome editing in pluripotent stem cells.

    Science.gov (United States)

    Yu, Chen; Liu, Yanxia; Ma, Tianhua; Liu, Kai; Xu, Shaohua; Zhang, Yu; Liu, Honglei; La Russa, Marie; Xie, Min; Ding, Sheng; Qi, Lei S

    2015-02-05

    The bacterial CRISPR-Cas9 system has emerged as an effective tool for sequence-specific gene knockout through non-homologous end joining (NHEJ), but it remains inefficient for precise editing of genome sequences. Here we develop a reporter-based screening approach for high-throughput identification of chemical compounds that can modulate precise genome editing through homology-directed repair (HDR). Using our screening method, we have identified small molecules that can enhance CRISPR-mediated HDR efficiency, 3-fold for large fragment insertions and 9-fold for point mutations. Interestingly, we have also observed that a small molecule that inhibits HDR can enhance frame shift insertion and deletion (indel) mutations mediated by NHEJ. The identified small molecules function robustly in diverse cell types with minimal toxicity. The use of small molecules provides a simple and effective strategy to enhance precise genome engineering applications and facilitates the study of DNA repair mechanisms in mammalian cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Expression of the Grb2-related protein of the lymphoid system in B cell subsets enhances B cell antigen receptor signaling through mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Yankee, Thomas M; Solow, Sasha A; Draves, Kevin D; Clark, Edward A

    2003-01-01

    Adapter proteins play a critical role in regulating signals triggered by Ag receptor cross-linking. These small molecules link receptor proximal events with downstream signaling pathways. In this study, we explore the expression and function of the Grb2-related protein of the lymphoid system (GrpL)/Grb2-related adaptor downstream of Shc adapter protein in human B cells. GrpL is expressed in naive B cells and is down-regulated following B cell Ag receptor ligation. By contrast, germinal center and memory B cells express little or no GrpL. Using human B cell lines, we detected constitutive interactions between GrpL and B cell linker protein, Src homology (SH)2 domain-containing leukocyte protein of 76 kDa, hemopoietic progenitor kinase 1, and c-Cbl. The N-terminal SH3 domain of GrpL binds c-Cbl while the C-terminal SH3 domain binds B cell linker protein and SH2 domain-containing leukocyte protein of 76 kDa. Exogenous expression of GrpL in a GrpL-negative B cell line leads to enhanced Ag receptor-induced extracellular signal-related kinase and p38 mitogen-activated protein kinase phosphorylation. Thus, GrpL expression in human B cell subsets appears to regulate Ag receptor-mediated signaling events.

  15. Adaptive remodeling of the biliary tree: the essence of liver progenitor cell expansion.

    Science.gov (United States)

    Kok, Cindy Yuet-Yin; Miyajima, Atsushi; Itoh, Tohru

    2015-07-01

    The liver progenitor cell population has long been thought to exist within the liver. However, there are no standardized criteria for defining the liver progenitor cells, and there has been intense debate about the origin of these cells in the adult liver. The characteristics of such cells vary depending on the disease model used and also on the method of analysis. Visualization of three-dimensional biliary structures has revealed that the emergence of liver progenitor cells essentially reflects the adaptive remodeling of the hepatic biliary network in response to liver injury. We propose that the progenitor cell exists as a subpopulation in the biliary tree and show that the appearance of liver progenitor cells in injured parenchyma is reflective of extensive remodeling of the biliary structure. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  16. Cell elongation is an adaptive response for clearing long chromatid arms from the cleavage plane

    Science.gov (United States)

    Kotadia, Shaila; Montembault, Emilie; Sullivan, William

    2012-01-01

    Chromosome segregation must be coordinated with cell cleavage to ensure correct transmission of the genome to daughter cells. Here we identify a novel mechanism by which Drosophila melanogaster neuronal stem cells coordinate sister chromatid segregation with cleavage furrow ingression. Cells adapted to a dramatic increase in chromatid arm length by transiently elongating during anaphase/telophase. The degree of cell elongation correlated with the length of the trailing chromatid arms and was concomitant with a slight increase in spindle length and an enlargement of the zone of cortical myosin distribution. Rho guanine-nucleotide exchange factor (Pebble)–depleted cells failed to elongate during segregation of long chromatids. As a result, Pebble-depleted adult flies exhibited morphological defects likely caused by cell death during development. These studies reveal a novel pathway linking trailing chromatid arms and cortical myosin that ensures the clearance of chromatids from the cleavage plane at the appropriate time during cytokinesis, thus preserving genome integrity. PMID:23185030

  17. The acquisition of mechano-electrical transducer current adaptation in auditory hair cells requires myosin VI

    NARCIS (Netherlands)

    Marcotti, Walter; Corns, Laura F.; Goodyear, Richard J.; Rzadzinska, Agnieszka K.; Avraham, Karen B.; Steel, Karen P.; Richardson, Guy P.; Kros, Corne J.

    2016-01-01

    The transduction of sound into electrical signals occurs at the hair bundles atop sensory hair cells in the cochlea, by means of mechanosensitive ion channels, the mechano-electrical transducer (MET) channels. The MET currents decline during steady stimuli; this is termed adaptation and ensures they

  18. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

    Science.gov (United States)

    Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

  19. Biomaterials that promote cell-cell interactions enhance the paracrine function of MSCs.

    Science.gov (United States)

    Qazi, Taimoor H; Mooney, David J; Duda, Georg N; Geissler, Sven

    2017-09-01

    Mesenchymal stromal cells (MSCs) secrete paracrine factors that play crucial roles during tissue regeneration. Whether this paracrine function is influenced by the properties of biomaterials in general, and those used for cell delivery in particular, largely remains unexplored. Here, we investigated if three-dimensional culture in distinct microenvironments - nanoporous hydrogels (mean pore size ∼5 nm) and macroporous scaffolds (mean pore size ∼120 μm) - affects the secretion pattern of MSCs, and consequently leads to differential paracrine effects on target progenitor cells such as myoblasts. We report that compared to MSCs encapsulated in hydrogels, scaffold seeded MSCs show an enhanced secretion profile and exert beneficial paracrine effects on various myoblast functions including migration and proliferation. Additionally, we show that the heightened paracrine effects of scaffold seeded cells can in part be attributed to N-cadherin mediated cell-cell interactions during culture. In hydrogels, this physical interaction between cells is prevented by the encapsulating matrix. Functionally blocking N-cadherin negatively affected the secretion profile and paracrine effects of MSCs on myoblasts, with stronger effects observed for scaffold seeded compared to hydrogel encapsulated cells. Together, these findings demonstrate that the therapeutic potency of MSCs can be enhanced by biomaterials that promote cell-cell interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Keto-adaptation enhances exercise performance and body composition responses to training in endurance athletes.

    Science.gov (United States)

    McSwiney, Fionn T; Wardrop, Bruce; Hyde, Parker N; Lafountain, Richard A; Volek, Jeff S; Doyle, Lorna

    2018-04-01

    Low-carbohydrate diets have recently grown in popularity among endurance athletes, yet little is known about the long-term (>4wk) performance implications of consuming a low-carbohydrate high fat ketogenic diet (LCKD) in well-trained athletes. Twenty male endurance-trained athletes (age 33±11y, body mass 80±11kg; BMI 24.7±3.1kg/m 2 ) who habitually consumed a carbohydrate-based diet, self-selected into a high-carbohydrate (HC) group (n=11, %carbohydrate:protein:fat=65:14:20), or a LCKD group (n=9, 6:17:77). Both groups performed the same training intervention (endurance, strength and high intensity interval training (HIIT)). Prior to and following successful completion of 12-weeks of diet and training, participants had their body composition assessed, and completed a 100km time trial (TT), six second (SS) sprint, and a critical power test (CPT). During post-intervention testing the HC group consumed 30-60g/h carbohydrate, whereas the LCKD group consumed water, and electrolytes. The LCKD group experienced a significantly greater decrease in body mass (HC -0.8kg, LCKD -5.9kg; P=0.006, effect size (ES): 0.338) and percentage body fat percentage (HC -0.7%, LCKD -5.2%; P=0.008, ES: 0.346). Fasting serum beta-hydroxybutyrate (βHB) significantly increased from 0.1 at baseline to 0.5mmol/L in the LCKD group (P=0.011, ES: 0.403) in week 12. There was no significant change in performance of the 100km TT between groups (HC -1.13min·s, LCKD -4.07min·s, P=0.057, ES: 0.196). SS sprint peak power increased by 0.8 watts per kilogram bodyweight (w/kg) in the LCKD group, versus a -0.1w/kg reduction in the HC group (P=0.025, ES: 0.263). CPT peak power decreased by -0.7w/kg in the HC group, and increased by 1.4w/kg in the LCKD group (P=0.047, ES: 0.212). Fat oxidation in the LCKD group was significantly greater throughout the 100km TT. Compared to a HC comparison group, a 12-week period of keto-adaptation and exercise training, enhanced body composition, fat oxidation during

  1. T cells enhance gold nanoparticle delivery to tumors in vivo

    Science.gov (United States)

    Kennedy, Laura C.; Bear, Adham S.; Young, Joseph K.; Lewinski, Nastassja A.; Kim, Jean; Foster, Aaron E.; Drezek, Rebekah A.

    2011-12-01

    Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

  2. Dendritic cells modulate burn wound healing by enhancing early proliferation.

    Science.gov (United States)

    Vinish, Monika; Cui, Weihua; Stafford, Eboni; Bae, Leon; Hawkins, Hal; Cox, Robert; Toliver-Kinsky, Tracy

    2016-01-01

    Adequate wound healing is vital for burn patients to reduce the risk of infections and prolonged hospitalization. Dendritic cells (DCs) are antigen presenting cells that release cytokines and are central for the activation of innate and acquired immune responses. Studies have showed their presence in human burn wounds; however, their role in burn wound healing remains to be determined. This study investigated the role of DCs in modulating healing responses within the burn wound. A murine model of full-thickness contact burns was used to study wound healing in the absence of DCs (CD11c promoter-driven diphtheria toxin receptor transgenic mice) and in a DC-rich environment (using fms-like tyrosine kinase-3 ligand, FL- a DC growth factor). Wound closure was significantly delayed in DC-deficient mice and was associated with significant suppression of early cellular proliferation, granulation tissue formation, wound levels of TGFβ1 and formation of CD31+ vessels in healing wounds. In contrast, DC enhancement significantly accelerated early wound closure, associated with increased and accelerated cellular proliferation, granulation tissue formation, and increased TGFβ1 levels and CD31+ vessels in healing wounds. We conclude that DCs play an important role in the acceleration of early wound healing events, likely by secreting factors that trigger the proliferation of cells that mediate wound healing. Therefore, pharmacological enhancement of DCs may provide a therapeutic intervention to facilitate healing of burn wounds. © 2016 by the Wound Healing Society.

  3. Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.

    Directory of Open Access Journals (Sweden)

    Zhen Hua Wu

    Full Text Available The major challenges we are facing in cancer therapy with paclitaxel (PTX are the drug resistance and severe side effects. Massive efforts have been made to overcome these clinical challenges by combining PTX with other drugs. In this study, we reported the first preclinical data that praziquantel (PZQ, an anti-parasite agent, could greatly enhance the anticancer efficacy of PTX in various cancer cell lines, including PTX-resistant cell lines. Based on the combination index value, we demonstrated that PZQ synergistically enhanced PTX-induced cell growth inhibition. The co-treatment of PZQ and PTX also induced significant mitotic arrest and activated the apoptotic cascade. Moreover, PZQ combined with PTX resulted in a more pronounced inhibition of tumor growth compared with either drug alone in a mouse xenograft model. We tried to investigate the possible mechanisms of this synergistic efficacy induced by PZQ and PTX, and we found that the co-treatment of the two drugs could markedly decrease expression of X-linked inhibitor of apoptosis protein (XIAP, an anti-apoptotic protein. Our data further demonstrated that down-regulation of XIAP was required for the synergistic interaction between PZQ and PTX. Together, this study suggested that the combination of PZQ and PTX may represent a novel and effective anticancer strategy for optimizing PTX therapy.

  4. Positively charged residues at the five-fold symmetry axis of cell culture-adapted foot-and-mouth disease virus permit novel receptor interactions.

    Science.gov (United States)

    Berryman, Stephen; Clark, Stuart; Kakker, Naresh K; Silk, Rhiannon; Seago, Julian; Wadsworth, Jemma; Chamberlain, Kyle; Knowles, Nick J; Jackson, Terry

    2013-08-01

    Field isolates of foot-and-mouth disease virus (FMDV) have a restricted cell tropism which is limited by the need for certain RGD-dependent integrin receptors. In contrast, cell culture-adapted viruses use heparan sulfate (HS) or other unidentified molecules as receptors to initiate infection. Here, we report several novel findings resulting from cell culture adaptation of FMDV. In cell culture, a virus with the capsid of the A/Turkey/2/2006 field isolate gained the ability to infect CHO and HS-deficient CHO cells as a result of a single glutamine (Q)-to-lysine (K) substitution at VP1-110 (VP1-(Q)110(K)). Using site-directed mutagenesis, the introduction of lysine at this same site also resulted in an acquired ability to infect CHO cells by type O and Asia-1 FMDV. However, this ability appeared to require a second positively charged residue at VP1-109. CHO cells express two RGD-binding integrins (α5β1 and αvβ5) that, although not used by FMDV, have the potential to be used as receptors; however, viruses with the VP1-(Q)110(K) substitution did not use these integrins. In contrast, the VP1-(Q)110(K) substitution appeared to result in enhanced interactions with αvβ6, which allowed a virus with KGE in place of the normal RGD integrin-binding motif to use αvβ6 as a receptor. Thus, our results confirmed the existence of nonintegrin, non-HS receptors for FMDV on CHO cells and revealed a novel, non-RGD-dependent use of αvβ6 as a receptor. The introduction of lysine at VP1-110 may allow for cell culture adaptation of FMDV by design, which may prove useful for vaccine manufacture when cell culture adaptation proves intractable.

  5. Positively Charged Residues at the Five-Fold Symmetry Axis of Cell Culture-Adapted Foot-and-Mouth Disease Virus Permit Novel Receptor Interactions

    Science.gov (United States)

    Berryman, Stephen; Clark, Stuart; Kakker, Naresh K.; Silk, Rhiannon; Seago, Julian; Wadsworth, Jemma; Chamberlain, Kyle; Knowles, Nick J.

    2013-01-01

    Field isolates of foot-and-mouth disease virus (FMDV) have a restricted cell tropism which is limited by the need for certain RGD-dependent integrin receptors. In contrast, cell culture-adapted viruses use heparan sulfate (HS) or other unidentified molecules as receptors to initiate infection. Here, we report several novel findings resulting from cell culture adaptation of FMDV. In cell culture, a virus with the capsid of the A/Turkey/2/2006 field isolate gained the ability to infect CHO and HS-deficient CHO cells as a result of a single glutamine (Q)-to-lysine (K) substitution at VP1-110 (VP1-Q110K). Using site-directed mutagenesis, the introduction of lysine at this same site also resulted in an acquired ability to infect CHO cells by type O and Asia-1 FMDV. However, this ability appeared to require a second positively charged residue at VP1-109. CHO cells express two RGD-binding integrins (α5β1 and αvβ5) that, although not used by FMDV, have the potential to be used as receptors; however, viruses with the VP1-Q110K substitution did not use these integrins. In contrast, the VP1-Q110K substitution appeared to result in enhanced interactions with αvβ6, which allowed a virus with KGE in place of the normal RGD integrin-binding motif to use αvβ6 as a receptor. Thus, our results confirmed the existence of nonintegrin, non-HS receptors for FMDV on CHO cells and revealed a novel, non-RGD-dependent use of αvβ6 as a receptor. The introduction of lysine at VP1-110 may allow for cell culture adaptation of FMDV by design, which may prove useful for vaccine manufacture when cell culture adaptation proves intractable. PMID:23740982

  6. In vitro effects of piracetam on the radiosensitivity of hypoxic cells (adaptation of MTT assay to hypoxic conditions)

    International Nuclear Information System (INIS)

    Gheuens, E.E.O.; Bruijn, E.A. de; Van der Heyden, S.; Van Oosterom, A.T.; Lagarde, P.; Pooter, C.M.J. de; Chomy, F.

    1995-01-01

    This paper describes the adaptation of the MTT assay to hypoxic conditions in order to test the in vitro effect of piracetam on hypoxic cells and particularly on the radiosensitivity of hypoxic cells since this drug has shown clinical effect on acute and chronic hypoxia. The V79 cell line was selected by reference to preliminary hypoxic experiments using clonogenic assay and euoxic experiments using clonogenic and MTT assays. Cell growth and survival in our hypoxic conditions were assessed using MTT assay with an enclosure and special 48-well plates both made of glass. Growth curves on glass plates after 1-hour exposure to nitrogen versus air were comparable, so there is no bias effect due to gas composition. Survival curves using MTT versus reference clonogenic assay were comparable after radiation exposure in eu- and hypoxic conditions, and confirm the validity of our original technique for creating hypoxia. The Oxygen Enhancement Ratio was of about 3 for 1-hour hypoxic exposure. Piracetam gave no cytotoxic effect up to 10 mM of piracetam. Growth curves after continuous drug exposure and 1-hour euoxic versus hypoxic exposure gave no cytotoxic effect up to 10 mM of piracetam. Survival curves after continuous drug exposure to 10 mM of piracetam gave no significant effect on the radiosensitivity of hypoxic V79 cells using MTT or clonogenic assay. (author). 32 refs., 6 figs

  7. Parameter extraction of different fuel cell models with transferred adaptive differential evolution

    International Nuclear Information System (INIS)

    Gong, Wenyin; Yan, Xuesong; Liu, Xiaobo; Cai, Zhihua

    2015-01-01

    To improve the design and control of FC (fuel cell) models, it is important to extract their unknown parameters. Generally, the parameter extraction problems of FC models can be transformed as nonlinear and multi-variable optimization problems. To extract the parameters of different FC models exactly and fast, in this paper, we propose a transferred adaptive DE (differential evolution) framework, in which the successful parameters of the adaptive DE solving previous problems are properly transferred to solve new optimization problems in the similar problem-domains. Based on this framework, an improved adaptive DE method (TRADE, in short) is presented as an illustration. To verify the performance of our proposal, TRADE is used to extract the unknown parameters of two types of fuel cell models, i.e., PEMFC (proton exchange membrane fuel cell) and SOFC (solid oxide fuel cell). The results of TRADE are also compared with those of other state-of-the-art EAs (evolutionary algorithms). Even though the modification is very simple, the results indicate that TRADE can extract the parameters of both PEMFC and SOFC models exactly and fast. Moreover, the V–I characteristics obtained by TRADE agree well with the simulated and experimental data in all cases for both types of fuel cell models. Also, it improves the performance of the original adaptive DE significantly in terms of both the quality of final solutions and the convergence speed in all cases. Additionally, TRADE is able to provide better results compared with other EAs. - Highlights: • A framework of transferred adaptive differential evolution is proposed. • Based on the framework, an improved differential evolution (TRADE) is presented. • TRADE obtains very promising results to extract the parameters of PEMFC and SOFC models

  8. Hypoxic enhancement of exosome release by breast cancer cells

    International Nuclear Information System (INIS)

    King, Hamish W; Michael, Michael Z; Gleadle, Jonathan M

    2012-01-01

    Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour progression, angiogenesis and metastasis, potentially through exosome-mediated signalling. Breast cancer cell lines were cultured under either moderate (1% O 2 ) or severe (0.1% O 2 ) hypoxia. Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA) and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by real-time reverse transcription polymerase chain reaction and normalised to exogenous and endogenous control genes. Statistical significance was determined using the Student T test with a P value of < 0.05 considered significant. Exposure of three different breast cancer cell lines to moderate (1% O 2 ) and severe (0.1% O 2 ) hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a hypoxia-inducible factor (HIF) hydroxylase inhibitor, resulted in significant increase in exosome release. Transfection of cells with HIF-1α siRNA prior to hypoxic exposure prevented the enhancement of exosome release by hypoxia. The hypoxically regulated miR-210 was identified to be present at elevated levels in hypoxic exosome fractions. These data provide evidence that hypoxia promotes the release of exosomes by breast cancer cells, and that this hypoxic response may be mediated by HIF-1α. Given an emerging role for tumour cell-derived exosomes in tumour progression, this has significant implications for understanding the hypoxic tumour phenotype, whereby hypoxic cancer cells may release

  9. Enhancement tuning and control for high dynamic range images in multi-scale locally adaptive contrast enhancement algorithms

    Science.gov (United States)

    Cvetkovic, Sascha D.; Schirris, Johan; de With, Peter H. N.

    2009-01-01

    For real-time imaging in surveillance applications, visibility of details is of primary importance to ensure customer confidence. If we display High Dynamic-Range (HDR) scenes whose contrast spans four or more orders of magnitude on a conventional monitor without additional processing, results are unacceptable. Compression of the dynamic range is therefore a compulsory part of any high-end video processing chain because standard monitors are inherently Low- Dynamic Range (LDR) devices with maximally two orders of display dynamic range. In real-time camera processing, many complex scenes are improved with local contrast enhancements, bringing details to the best possible visibility. In this paper, we show how a multi-scale high-frequency enhancement scheme, in which gain is a non-linear function of the detail energy, can be used for the dynamic range compression of HDR real-time video camera signals. We also show the connection of our enhancement scheme to the processing way of the Human Visual System (HVS). Our algorithm simultaneously controls perceived sharpness, ringing ("halo") artifacts (contrast) and noise, resulting in a good balance between visibility of details and non-disturbance of artifacts. The overall quality enhancement, suitable for both HDR and LDR scenes, is based on a careful selection of the filter types for the multi-band decomposition and a detailed analysis of the signal per frequency band.

  10. Metabolic Plasticity of Metastatic Breast Cancer Cells: Adaptation to Changes in the Microenvironment

    Directory of Open Access Journals (Sweden)

    Rui V. Simões

    2015-08-01

    Full Text Available Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer cells lines (highly metastatic 4T1; nonmetastatic 67NR to identify differences in their glucose and glutamine metabolism in response to metabolic and environmental stress. Dynamic magnetic resonance spectroscopy of 13C-isotopomers showed that 4T1 cells have higher glycolytic and tricarboxylic acid (TCA cycle flux than 67NR cells and readily switch between glycolysis and oxidative phosphorylation (OXPHOS in response to different extracellular environments. OXPHOS activity increased with metastatic potential in isogenic cell lines derived from the same primary breast cancer: 4T1 > 4T07 and 168FARN (local micrometastasis only > 67NR. We observed a restricted TCA cycle flux at the succinate dehydrogenase step in 67NR cells (but not in 4T1 cells, leading to succinate accumulation and hindering OXPHOS. In the four isogenic cell lines, environmental stresses modulated succinate dehydrogenase subunit A expression according to metastatic potential. Moreover, glucose-derived lactate production was more glutamine dependent in cell lines with higher metastatic potential. These studies show clear differences in TCA cycle metabolism between 4T1 and 67NR breast cancer cells. They indicate that metastases-forming 4T1 cells are more adept at adjusting their metabolism in response to environmental stress than isogenic, nonmetastatic 67NR cells. We suggest that the metabolic plasticity and adaptability are more important to the metastatic breast cancer phenotype than rapid cell proliferation alone, which could 1 provide a new biomarker for early detection of this phenotype, possibly at the time of diagnosis, and 2 lead to new treatment strategies of metastatic breast cancer by targeting mitochondrial metabolism.

  11. Modeling nanostructure-enhanced light trapping in organic solar cells

    DEFF Research Database (Denmark)

    Adam, Jost

    A promising approach for improving the power conversion efficiencies of organic solar cells (OSCs) is by incorporating nanostructures in their thin film architecture to improve the light absorption in the device’s active polymer layers. Here, we present a modelling framework for the prediction...... of optical and plasmonic field enhancement by nanostructures in (or close to) the active layers and electrodes in OSCs. We incorporate finite-difference time-domain (FDTD) calculations alongside semi- analytical approaches, as the rigorous coupled-wave analysis (RCWA) and mode-coupling theory. Our simulation...

  12. The CWI Pathway: Regulation of the Transcriptional Adaptive Response to Cell Wall Stress in Yeast

    Directory of Open Access Journals (Sweden)

    Ana Belén Sanz

    2017-12-01

    Full Text Available Fungi are surrounded by an essential structure, the cell wall, which not only confers cell shape but also protects cells from environmental stress. As a consequence, yeast cells growing under cell wall damage conditions elicit rescue mechanisms to provide maintenance of cellular integrity and fungal survival. Through transcriptional reprogramming, yeast modulate the expression of genes important for cell wall biogenesis and remodeling, metabolism and energy generation, morphogenesis, signal transduction and stress. The yeast cell wall integrity (CWI pathway, which is very well conserved in other fungi, is the key pathway for the regulation of this adaptive response. In this review, we summarize the current knowledge of the yeast transcriptional program elicited to counterbalance cell wall stress situations, the role of the CWI pathway in the regulation of this program and the importance of the transcriptional input received by other pathways. Modulation of this adaptive response through the CWI pathway by positive and negative transcriptional feedbacks is also discussed. Since all these regulatory mechanisms are well conserved in pathogenic fungi, improving our knowledge about them will have an impact in the developing of new antifungal therapies.

  13. Cross case analysis of institutions and adaptive capacity in The Netherlands: Do institutions for spatial planning, water and nature management in The Netherlands enhance the capacity of society to adapt to climate change?

    NARCIS (Netherlands)

    Meijerink, S.; Bergsma, E.; Gupta, J.; Jong, P.; Klostermann, J.E.M.; Termeer, C.J.A.M.

    2010-01-01

    In this working document we aim to answer the following question: Do institutions for spatial planning, water and nature management in the Netherlands enhance the capacity of society to adapt to climate change? To answer this question we have first reviewed the literature on adaptive governance and

  14. Cellular cooperation in lymphocyte activation. III. B-cell helper effect in the enhancement of T-cell response.

    Science.gov (United States)

    Kasahara, T; Kin, K; Itoh, Y; Kawai, T; Kano, Y; Shioiri-Nakano, K

    1979-01-01

    T and B cells were purified from human tonsil and peripheral blood by the removal of phagocytic cells, followed by filtration through a nylon fiber column (NC) and E-rosette formation. Purified T and B cells contained less than 1% of other cell types. The responses of T cells to concanavalin A (Con A) and soluble protein A were greatly enhanced in the presence of autologous B cells. Participation of B cells in T-cell enhancement was confirmed by the following observations: (a) purified B copulation, which was separated further from adherent B cells, retained its enhancing activity. (b) Another adherent cell-free B-cell preparation, which was purified from the NC-passed fraction, and (c) no T lymphoid but some B lymphoid cell lines, elicited strong T-cell enhancement. It was also found that the enhancing capacity of B cells required no metabolic activity, but rather an intact cell form and direct cell-to-cell contact with responding cells. The stimulatory determinants on B cells were resistant to trypsin and neuraminidase treatment. In this paper a hypothesis will be presented that at least two signals are prerequisite for the effective activation of T cells.

  15. BRE enhances in vivo growth of tumor cells

    International Nuclear Information System (INIS)

    Chan, Ben Chung-Lap; Li Qing; Chow, Stephanie Ka-Yee; Ching, Arthur Kar-Keung; Liew, Choong Tsek; Lim, Pak-Leong; Lee, Kenneth Ka-Ho; Chan, John Yeuk-Hon; Chui, Y.-L.

    2005-01-01

    Human BRE, a death receptor-associating intracellular protein, attenuates apoptotic response of human and mouse tumor cell lines to death receptor stimuli in vitro. In this report, we addressed whether the in vitro antiapoptotic effect of BRE could impact on tumor growth in vivo. We have shown that the mouse Lewis lung carcinoma D122 stable transfectants of human BRE expression vector developed into local tumor significantly faster than the stable transfectants of empty vector and parental D122, in both the syngeneic C57BL/6 host and nude mice. In vitro growth of the BRE stable transfectants was, however, not accelerated. No significant difference in metastasis between the transfectants and the parental D122 was detected. Thus, overexpression of BRE promotes local tumor growth but not metastasis. We conclude that the enhanced tumor growth is more likely due to the antiapoptotic activity of BRE than any direct effect of the protein on cell proliferation

  16. Cytogenetic adaptive response of mouse bone marrow cells to low level HTO

    International Nuclear Information System (INIS)

    Chen Deqing; Zhang Zhaoyang; Zhou Xiangyan

    1993-01-01

    Mice were abdominally injected with a adaptive dose of 3.7 x 10 2 -3.7 x 10 5 Bq/gbw HTO, and then exposed to a challenge dose of 1.5 Gy of 6 '0Co γ-rays. In bone marrow cells that received both the adaptive and challenge doses, the chromatid breaks are lower than expected on the basis of additivity of the effects of the individual treatment. The adaptive response induced with 3.7 x 10 3 Bq/gbw HTO is the most remarkable, but at 3.7 x 10 5 Bq/gbw the adaptive response seems to disappear. The adaptive response can be observed by exposing to 1.5 Gy γ-rays from 1 to 5 days after injection of 3.7 x 10 3 Bq/gbw HTO, which is the most obvious one to reduce chromatid breaks to 50% of expected at the 5th day, but at the 7th day to equate to expected. The frequency of chromatid breaks is gradually reduced with time after challenge dose, the maximum index number of adaptive response is 0.50 and appears at 24 hr after challenge dose

  17. Genetic modification of embryonic stem cells with VEGF enhances cell survival and improves cardiac function.

    Science.gov (United States)

    Xie, Xiaoyan; Cao, Feng; Sheikh, Ahmad Y; Li, Zongjin; Connolly, Andrew J; Pei, Xuetao; Li, Ren-Ke; Robbins, Robert C; Wu, Joseph C

    2007-01-01

    Cardiac stem cell therapy remains hampered by acute donor cell death posttransplantation and the lack of reliable methods for tracking cell survival in vivo. We hypothesize that cells transfected with inducible vascular endothelial growth factor 165 (VEGF(165)) can improve their survival as monitored by novel molecular imaging techniques. Mouse embryonic stem (ES) cells were transfected with an inducible, bidirectional tetracycline (Bi-Tet) promoter driving VEGF(165) and renilla luciferase (Rluc). Addition of doxycycline induced Bi-Tet expression of VEGF(165) and Rluc significantly compared to baseline (p<0.05). Expression of VEGF(165) enhanced ES cell proliferation and inhibited apoptosis as determined by Annexin-V staining. For noninvasive imaging, ES cells were transduced with a double fusion (DF) reporter gene consisting of firefly luciferase and enhanced green fluorescence protein (Fluc-eGFP). There was a robust correlation between cell number and Fluc activity (R(2)=0.99). Analysis by immunostaining, histology, and RT-PCR confirmed that expression of Bi-Tet and DF systems did not affect ES cell self-renewal or pluripotency. ES cells were differentiated into beating embryoid bodies expressing cardiac markers such as troponin, Nkx2.5, and beta-MHC. Afterward, 5 x 10(5) cells obtained from these beating embryoid bodies or saline were injected into the myocardium of SV129 mice (n=36) following ligation of the left anterior descending (LAD) artery. Bioluminescence imaging (BLI) and echocardiography showed that VEGF(165) induction led to significant improvements in both transplanted cell survival and cardiac function (p<0.05). This is the first study to demonstrate imaging of embryonic stem cell-mediated gene therapy targeting cardiovascular disease. With further validation, this platform may have broad applications for current basic research and further clinical studies.

  18. Surface-Enhanced Raman Scattering Nanoparticles as Optical Labels for Imaging Cell Surface Proteins

    Science.gov (United States)

    MacLaughlin, Christina M.

    Assaying the expression of cell surface proteins has widespread application for characterizing cell type, developmental stage, and monitoring disease transformation. Immunophenotyping is conducted by treating cells with labelled targeting moieties that have high affinity for relevant surface protein(s). The sensitivity and specificity of immunophenotyping is defined by the choice of contrast agent and therefore, the number of resolvable signals that can be used to simultaneously label cells. Narrow band width surface-enhanced Raman scattering (SERS) nanoparticles are proposed as optical labels for multiplexed immunophenotying. Two types of surface coatings were investigated to passivate the gold nanoparticles, incorporate SERS functionality, and to facilitate attachment of targeting antibodies. Thiolated poly(ethylene glycol) forms dative bonds with the gold surface and is compatible with multiple physisorbed Raman-active reporter molecules. Ternary lipid bilayers are used to encapsulate the gold nanoparticles particles, and incorporate three different classes of Raman reporters. TEM, UV-Visible absorbance spectroscopy, DLS, and electrophoretic light scattering were used characterize the particle coating. Colourimetric protein assay, and secondary antibody labelling were used to quantify the antibody conjugation. Three different in vitromodels were used to investigate the binding efficacy and specificity of SERS labels for their biomarker targets. Primary human CLL cells, LY10 B lymphoma, and A549 adenocarcinoma lines were targeted. Dark field imaging was used to visualize the colocalization of SERS labels with cells, and evidence of receptor clustering was obtained based on colour shifts of the particles' Rayleigh scattering. Widefield, and spatially-resolved Raman spectra were used to detect labels singly, and in combination from labelled cells. Fluorescence flow cytometry was used to test the particles' binding specificity, and SERS from labelled cells was also

  19. Modeling of a HTPEM fuel cell using Adaptive Neuro-Fuzzy Inference Systems

    DEFF Research Database (Denmark)

    Justesen, Kristian Kjær; Andreasen, Søren Juhl; Sahlin, Simon Lennart

    2015-01-01

    In this work an Adaptive Neuro-Fuzzy Inference System (ANFIS) model of the voltage of a fuel cell is developed. The inputs of this model are the fuel cell temperature, current density and the carbon monoxide concentration of the anode supply gas. First an identification experiment which spans...... the expected operating range of the fuel cell is performed in a test station. The data from this experiment is then used to train ANFIS models with 2, 3, 4 and 5 membership functions. The performance of these models is then compared and it is found that using 3 membership functions provides the best compromise...

  20. Mechanical Adaptability of the MMP-Responsive Film Improves the Functionality of Endothelial Cell Monolayer.

    Science.gov (United States)

    Hu, Mi; Chang, Hao; Zhang, He; Wang, Jing; Lei, Wen-Xi; Li, Bo-Chao; Ren, Ke-Feng; Ji, Jian

    2017-07-01

    Extracellular matrix and cells are inherent in coordinating and adapting to each other during all physiological and pathological processes. Synthetic materials, however, show rarely reciprocal and spatiotemporal responses to cells, and lacking self-adapting properties as well. Here, a mechanical adaptability based on the matrix metalloproteinase (MMPs) sensitive polyelectrolyte film is reported. Poly-lysine (PLL) and methacrylated hyaluronic acid (HA-MA) nanolayers are employed to build the thin film through the layer-by-layer assembly, and it is further crosslinked using MMP sensitive peptides, which endows the films with changeable mechanical properties in response to MMPs. It is demonstrated that stiffness of the (PLL/HA-MA) films increases with the crosslinking, and then decreases in response to a treatment of enzyme. Consequently, the crosslinked (PLL/HA-MA) films reveal effective growth of endothelial cells (ECs), leading to fast formation of EC monolayer. Importantly, significantly improved endothelial function of the EC monolayer, which is characterized by integrity, biomolecules release, expression of function related gene, and antithrombotic properties, is achieved along with the decrosslinking of the film because of EC-secreted MMPs. These results suggest that mechanical adaptability of substrate in Young's modulus plays a significant role in endothelial progression, which shows great application potential in tissue engineering, regenerative medicine, and organ-on-a-chip. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Exogenous pyruvate facilitates cancer cell adaptation to hypoxia by serving as an oxygen surrogate.

    Science.gov (United States)

    Yin, Chengqian; He, Dan; Chen, Shuyang; Tan, Xiaoling; Sang, Nianli

    2016-07-26

    Molecular oxygen is the final electron acceptor in cellular metabolism but cancer cells often become adaptive to hypoxia, which promotes resistance to chemotherapy and radiation. The reduction of endogenous glycolytic pyruvate to lactate is known as an adaptive strategy for hypoxic cells. Whether exogenous pyruvate is required for hypoxic cell proliferation by either serving as an electron acceptor or a biosynthetic substrate remains unclear. By using both hypoxic and ρ0 cells defective in electron transfer chain, we show that exogenous pyruvate is required to sustain proliferation of both cancer and non-cancer cells that cannot utilize oxygen. Particularly, we show that absence of pyruvate led to glycolysis inhibition and AMPK activation along with decreased NAD+ levels in ρ0 cells; and exogenous pyruvate increases lactate yield, elevates NAD+/NADH ratio and suppresses AMPK activation. Knockdown of lactate dehydrogenase significantly inhibits the rescuing effects of exogenous pyruvate. In contrast, none of pyruvate-derived metabolites tested (including acetyl-CoA, α-ketoglutarate, succinate and alanine) can replace pyruvate in supporting ρ0 cell proliferation. Knockdown of pyruvate carboxylase, pyruvate dehydrogenase and citrate synthase do not impair exogenous pyruvate to rescue ρ0 cells. Importantly, we show that exogenous pyruvate relieves ATP insufficiency and mTOR inhibition and promotes proliferation of hypoxic cells, and that well-oxygenated cells release pyruvate, providing a potential in vivo source of pyruvate. Taken together, our data support a novel pyruvate cycle model in which oxygenated cells release pyruvate for hypoxic cells as an oxygen surrogate. The pyruvate cycle may be targeted as a new therapy of hypoxic cancers.

  2. A novel three-dimensional cell culture method enhances antiviral drug screening in primary human cells.

    Science.gov (United States)

    Koban, Robert; Neumann, Markus; Daugs, Aila; Bloch, Oliver; Nitsche, Andreas; Langhammer, Stefan; Ellerbrok, Heinz

    2018-02-01

    Gefitinib is a specific inhibitor of the epidermal growth factor receptor (EGFR) and FDA approved for treatment of non-small cell lung cancer. In a previous study we could show the in vitro efficacy of gefitinib for treatment of poxvirus infections in monolayer (2D) cultivated cell lines. Permanent cell lines and 2D cultures, however, are known to be rather unphysiological; therefore it is difficult to predict whether determined effective concentrations or the drug efficacy per se are transferable to the in vivo situation. 3D cell cultures, which meanwhile are widely distributed across all fields of research, are a promising tool for more predictive in vitro investigations of antiviral compounds. In this study the spreading of cowpox virus and the antiviral efficacy of gefitinib were analyzed in primary human keratinocytes (NHEK) grown in a novel 3D extracellular matrix-based cell culture model and compared to the respective monolayer culture. 3D-cultivated NHEK grew in a polarized and thus a more physiological manner with altered morphology and close cell-cell contact. Infected cultures showed a strongly elevated sensitivity towards gefitinib. EGFR phosphorylation, cell proliferation, and virus replication were significantly reduced in 3D cultures at gefitinib concentrations which were at least 100-fold lower than those in monolayer cultures and well below the level of cytotoxicity. Our newly established 3D cell culture model with primary human cells is an easy-to-handle alternative to conventional monolayer cell cultures and previously described more complex 3D cell culture systems. It can easily be adapted to other cell types and a broad spectrum of viruses for antiviral drug screening and many other aspects of virus research under more in vivo-like conditions. In consequence, it may contribute to a more targeted realization of necessary in vivo experiments. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Enhanced regeneration of degraded polymer solar cells by thermal annealing

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Pankaj, E-mail: pankaj@mail.nplindia.ernet.in [CSIR-National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi 110012 (India); Centre for Organic Electronics, Physics, University of Newcastle, Callaghan NSW-2308 (Australia); Bilen, Chhinder; Zhou, Xiaojing; Belcher, Warwick J.; Dastoor, Paul C., E-mail: Paul.Dastoor@newcastle.edu.au [Centre for Organic Electronics, Physics, University of Newcastle, Callaghan NSW-2308 (Australia); Feron, Krishna [Centre for Organic Electronics, Physics, University of Newcastle, Callaghan NSW-2308 (Australia); CSIRO Energy Technology, P. O. Box 330, Newcastle NSW 2300 (Australia)

    2014-05-12

    The degradation and thermal regeneration of poly(3-hexylethiophene) (P3HT):[6,6]-phenyl-C{sub 61}-butyric acid methyl ester (PCBM) and P3HT:indene-C{sub 60} bisadduct (ICBA) polymer solar cells, with Ca/Al and Ca/Ag cathodes and indium tin oxide/poly(ethylene-dioxythiophene):polystyrene sulfonate anode have been investigated. Degradation occurs via a combination of three primary pathways: (1) cathodic oxidation, (2) active layer phase segregation, and (3) anodic diffusion. Fully degraded devices were subjected to thermal annealing under inert atmosphere. Degraded solar cells possessing Ca/Ag electrodes were observed to regenerate their performance, whereas solar cells having Ca/Al electrodes exhibited no significant regeneration of device characteristics after thermal annealing. Moreover, the solar cells with a P3HT:ICBA active layer exhibited enhanced regeneration compared to P3HT:PCBM active layer devices as a result of reduced changes to the active layer morphology. Devices combining a Ca/Ag cathode and P3HT:ICBA active layer demonstrated ∼50% performance restoration over several degradation/regeneration cycles.

  4. Enhanced regeneration of degraded polymer solar cells by thermal annealing

    International Nuclear Information System (INIS)

    Kumar, Pankaj; Bilen, Chhinder; Zhou, Xiaojing; Belcher, Warwick J.; Dastoor, Paul C.; Feron, Krishna

    2014-01-01

    The degradation and thermal regeneration of poly(3-hexylethiophene) (P3HT):[6,6]-phenyl-C 61 -butyric acid methyl ester (PCBM) and P3HT:indene-C 60 bisadduct (ICBA) polymer solar cells, with Ca/Al and Ca/Ag cathodes and indium tin oxide/poly(ethylene-dioxythiophene):polystyrene sulfonate anode have been investigated. Degradation occurs via a combination of three primary pathways: (1) cathodic oxidation, (2) active layer phase segregation, and (3) anodic diffusion. Fully degraded devices were subjected to thermal annealing under inert atmosphere. Degraded solar cells possessing Ca/Ag electrodes were observed to regenerate their performance, whereas solar cells having Ca/Al electrodes exhibited no significant regeneration of device characteristics after thermal annealing. Moreover, the solar cells with a P3HT:ICBA active layer exhibited enhanced regeneration compared to P3HT:PCBM active layer devices as a result of reduced changes to the active layer morphology. Devices combining a Ca/Ag cathode and P3HT:ICBA active layer demonstrated ∼50% performance restoration over several degradation/regeneration cycles

  5. A small-molecule/cytokine combination enhances hematopoietic stem cell proliferation via inhibition of cell differentiation.

    Science.gov (United States)

    Wang, Lan; Guan, Xin; Wang, Huihui; Shen, Bin; Zhang, Yu; Ren, Zhihua; Ma, Yupo; Ding, Xinxin; Jiang, Yongping

    2017-07-18

    Accumulated evidence supports the potent stimulating effects of multiple small molecules on the expansion of hematopoietic stem cells (HSCs) which are important for the therapy of various hematological disorders. Here, we report a novel, optimized formula, named the SC cocktail, which contains a combination of three such small molecules and four cytokines. Small-molecule candidates were individually screened and then combined at their optimal concentration with the presence of cytokines to achieve maximum capacity for stimulating the human CD34 + cell expansion ex vivo. The extent of cell expansion and the immunophenotype of expanded cells were assessed through flow cytometry. The functional preservation of HSC stemness was confirmed by additional cell and molecular assays in vitro. Subsequently, the expanded cells were transplanted into sublethally irradiated NOD/SCID mice for the assessment of human cell viability and engraftment potential in vivo. Furthermore, the expression of several genes in the cell proliferation and differentiation pathways was analyzed through quantitative polymerase chain reaction (qPCR) during the process of CD34 + cell expansion. The SC cocktail supported the retention of the immunophenotype of hematopoietic stem/progenitor cells remarkably well, by yielding purities of 86.6 ± 11.2% for CD34 + cells and 76.2 ± 10.5% for CD34 + CD38 - cells, respectively, for a 7-day culture. On day 7, the enhancement of expansion of CD34 + cells and CD34 + CD38 - cells reached a maxima of 28.0 ± 5.5-fold and 27.9 ± 4.3-fold, respectively. The SC cocktail-expanded CD34 + cells preserved the characteristics of HSCs by effectively inhibiting their differentiation in vitro and retained the multilineage differentiation potential in primary and secondary in vivo murine xenotransplantation trials. Further gene expression analysis suggested that the small-molecule combination strengthened the ability of the cytokines to enhance the Notch

  6. Application of adaptive digital signal processing to speech enhancement for the hearing impaired.

    Science.gov (United States)

    Chabries, D M; Christiansen, R W; Brey, R H; Robinette, M S; Harris, R W

    1987-01-01

    A major complaint of individuals with normal hearing and hearing impairments is a reduced ability to understand speech in a noisy environment. This paper describes the concept of adaptive noise cancelling for removing noise from corrupted speech signals. Application of adaptive digital signal processing has long been known and is described from a historical as well as technical perspective. The Widrow-Hoff LMS (least mean square) algorithm developed in 1959 forms the introduction to modern adaptive signal processing. This method uses a "primary" input which consists of the desired speech signal corrupted with noise and a second "reference" signal which is used to estimate the primary noise signal. By subtracting the adaptively filtered estimate of the noise, the desired speech signal is obtained. Recent developments in the field as they relate to noise cancellation are described. These developments include more computationally efficient algorithms as well as algorithms that exhibit improved learning performance. A second method for removing noise from speech, for use when no independent reference for the noise exists, is referred to as single channel noise suppression. Both adaptive and spectral subtraction techniques have been applied to this problem--often with the result of decreased speech intelligibility. Current techniques applied to this problem are described, including signal processing techniques that offer promise in the noise suppression application.

  7. Titanium phosphate glass microcarriers induce enhanced osteogenic cell proliferation and human mesenchymal stem cell protein expression

    Directory of Open Access Journals (Sweden)

    Nilay J Lakhkar

    2015-11-01

    Full Text Available In this study, we have developed 50- to 100-µm-sized titanium phosphate glass microcarriers (denoted as Ti5 that show enhanced proliferation of human mesenchymal stem cells and MG63 osteosarcoma cells, as well as enhanced human mesenchymal stem cell expression of bone differentiation markers, in comparison with commercially available glass microspheres at all time points. We also demonstrate that these microcarriers provide superior human mesenchymal stem cell proliferation with conventional Dulbecco’s Modified Eagle medium than with a specially developed commercial stem cell medium. The microcarrier proliferative capacity is revealed by a 24-fold increase in MG63 cell numbers in spinner flask bioreactor studies performed over a 7-day period, versus only a 6-fold increase in control microspheres under the same conditions; the corresponding values of Ti5 and control microspheres under static culture are 8-fold and 7-fold, respectively. The capability of guided osteogenic differentiation is confirmed by ELISAs for bone morphogenetic protein-2 and osteopontin, which reveal significantly greater expression of these markers, especially osteopontin, by human mesenchymal stem cells on the Ti5 microspheres than on the control. Scanning electron microscopy and confocal laser scanning microscopy images reveal favorable MG63 and human mesenchymal stem cell adhesion on the Ti5 microsphere surfaces. Thus, the results demonstrate the suitability of the developed microspheres for use as microcarriers in bone tissue engineering applications.

  8. Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness

    International Nuclear Information System (INIS)

    Xue, Jianguo; Zhu, Yuan; Sun, Zixuan; Ji, Runbi; Zhang, Xu; Xu, Wenrong; Yuan, Xiao; Zhang, Bin; Yan, Yongmin; Yin, Lei; Xu, Huijuan; Zhang, Leilei; Zhu, Wei; Qian, Hui

    2015-01-01

    Emerging evidence indicates that inappropriate cell-cell fusion might contribute to cancer progression. Similarly, mesenchymal stem cells (MSCs) can also fuse with other cells spontaneously and capable of adopting the phenotype of other cells. The aim of our study was to investigate the role of MSCs participated cell fusion in the tumorigenesis of gastric cancer. We fused human umbilical cord mesenchymal stem cells (hucMSCs) with gastric cancer cells in vitro by polyethylene glycol (PEG), the hybrid cells were sorted by flow cytometer. The growth and migration of hybrids were assessed by cell counting, cell colony formation and transwell assays. The proteins and genes related to epithelial-mesenchymal transition and stemness were tested by western blot, immunocytochemistry and real-time RT-PCR. The expression of CD44 and CD133 was examined by immunocytochemistry and flow cytometry. The xenograft assay was used to evaluation the tumorigenesis of the hybrids. The obtained hybrids exhibited epithelial- mesenchymal transition (EMT) change with down-regulation of E-cadherin and up-regulation of Vimentin, N-cadherin, α-smooth muscle actin (α-SMA), and fibroblast activation protein (FAP). The hybrids also increased expression of stemness factors Oct4, Nanog, Sox2 and Lin28. The expression of CD44 and CD133 on hybrid cells was stronger than parental gastric cancer cells. Moreover, the migration and proliferation of heterotypic hybrids were enhanced. In addition, the heterotypic hybrids promoted the growth abilities of gastric xenograft tumor in vivo. Taken together, our results suggest that cell fusion between hucMSCs and gastric cancer cells could contribute to tumorigenic hybrids with EMT and stem cell-like properties, which may provide a flexible tool for investigating the roles of MSCs in gastric cancer. The online version of this article (doi:10.1186/s12885-015-1780-1) contains supplementary material, which is available to authorized users

  9. Administration of a dipeptidyl peptidase IV inhibitor enhances the intestinal adaptation in a mouse model of short bowel syndrome

    DEFF Research Database (Denmark)

    Okawada, Manabu; Holst, Jens Juul; Teitelbaum, Daniel H

    2011-01-01

    Glucagon-like peptide-2 induces small intestine mucosal epithelial cell proliferation and may have benefit for patients who suffer from short bowel syndrome. However, glucagon-like peptide-2 is inactivated rapidly in vivo by dipeptidyl peptidase IV. Therefore, we hypothesized that selectively inh...... inhibiting dipeptidyl peptidase IV would prolong the circulating life of glucagon-like peptide-2 and lead to increased intestinal adaptation after development of short bowel syndrome....

  10. Gemcitabine enhances cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling.

    Science.gov (United States)

    Xu, Bao-Qing; Fu, Zhi-Guang; Meng, Yao; Wu, Xiao-Qing; Wu, Bo; Xu, Liang; Jiang, Jian-Li; Li, Ling; Chen, Zhi-Nan

    2016-09-20

    Pancreatic cancer, one of the most lethal cancers, has very poor 5-year survival partly due to gemcitabine resistance. Recently, it was reported that chemotherapeutic agents may act as stressors to induce adaptive responses and to promote chemoresistance in cancer cells. During long-term drug treatment, the minority of cancer cells survive and acquire an epithelial-mesenchymal transition phenotype with increased chemo-resistance and metastasis. However, the short-term response of most cancer cells remains unclear. This study aimed to investigate the short-term response of pancreatic cancer cells to gemcitabine stress and to explore the corresponding mechanism. Our results showed that gemcitabine treatment for 24 hours enhanced pancreatic cancer cell invasion. In gemcitabine-treated cells, HAb18G/CD147 was up-regulated; and HAb18G/CD147 down-regulation or inhibition attenuated gemcitabine-enhanced invasion. Mechanistically, HAb18G/CD147 promoted gemcitabine-enhanced invasion by activating the EGFR (epidermal growth factor receptor)-STAT3 (signal transducer and activator of transcription 3) signaling pathway. Inhibition of EGFR-STAT3 signaling counteracted gemcitabine-enhanced invasion, and which relied on HAb18G/CD147 levels. In pancreatic cancer tissues, EGFR was highly expressed and positively correlated with HAb18G/CD147. These data indicate that pancreatic cancer cells enhance cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling. Our findings suggest that inhibiting HAb18G/CD147 is a potential strategy for overcoming drug stress-associated resistance in pancreatic cancer.

  11. Electrical coupling between A17 cells enhances reciprocal inhibitory feedback to rod bipolar cells.

    Science.gov (United States)

    Elgueta, Claudio; Leroy, Felix; Vielma, Alex H; Schmachtenberg, Oliver; Palacios, Adrian G

    2018-02-15

    A17 amacrine cells are an important part of the scotopic pathway. Their synaptic varicosities receive glutamatergic inputs from rod bipolar cells (RBC) and release GABA onto the same RBC terminal, forming a reciprocal feedback that shapes RBC depolarization. Here, using patch-clamp recordings, we characterized electrical coupling between A17 cells of the rat retina and report the presence of strongly interconnected and non-coupled A17 cells. In coupled A17 cells, evoked currents preferentially flow out of the cell through GJs and cross-synchronization of presynaptic signals in a pair of A17 cells is correlated to their coupling degree. Moreover, we demonstrate that stimulation of one A17 cell can induce electrical and calcium transients in neighboring A17 cells, thus confirming a functional flow of information through electrical synapses in the A17 coupled network. Finally, blocking GJs caused a strong decrease in the amplitude of the inhibitory feedback onto RBCs. We therefore propose that electrical coupling between A17 cells enhances feedback onto RBCs by synchronizing and facilitating GABA release from inhibitory varicosities surrounding each RBC axon terminal. GJs between A17 cells are therefore critical in shaping the visual flow through the scotopic pathway.

  12. Enhancing and expanding intersectional research for climate change adaptation in agrarian settings.

    Science.gov (United States)

    Thompson-Hall, Mary; Carr, Edward R; Pascual, Unai

    2016-12-01

    Most current approaches focused on vulnerability, resilience, and adaptation to climate change frame gender and its influence in a manner out-of-step with contemporary academic and international development research. The tendency to rely on analyses of the sex-disaggregated gender categories of 'men' and 'women' as sole or principal divisions explaining the abilities of different people within a group to adapt to climate change, illustrates this problem. This framing of gender persists in spite of established bodies of knowledge that show how roles and responsibilities that influence a person´s ability to deal with climate-induced and other stressors emerge at the intersection of diverse identity categories, including but not limited to gender, age, seniority, ethnicity, marital status, and livelihoods. Here, we provide a review of relevant literature on this topic and argue that approaching vulnerability to climate change through intersectional understandings of identity can help improve adaptation programming, project design, implementation, and outcomes.

  13. Flexible Microgrid Power Quality Enhancement Using Adaptive Hybrid Voltage and Current Controller

    DEFF Research Database (Denmark)

    He, Jinwei; Li, Yun Wei; Blaabjerg, Frede

    2014-01-01

    -pass/bandpass filters in the DG unit digital controller. Moreover, phase-locked loops are not necessary as the microgrid frequency deviation can be automatically identified by the power control loop. Consequently, the proposed control method provides opportunities to reduce DG control complexity, without affecting......To accomplish superior harmonic compensation performance using distributed generation (DG) unit power electronics interfaces, an adaptive hybrid voltage and current controlled method (HCM) is proposed in this paper. It shows that the proposed adaptive HCM can reduce the numbers of low...... the harmonic compensation performance. Comprehensive simulated and experimental results from a single-phase microgrid are provided to verify the feasibility of the proposed adaptive HCM approach....

  14. TCSC Nonlinear Adaptive Damping Controller Design Based on RBF Neural Network to Enhance Power System Stability

    DEFF Research Database (Denmark)

    Yao, Wei; Fang, Jiakun; Zhao, Ping

    2013-01-01

    the characteristics of the conventional PID, but adjust the parameters of PID controller online using identified Jacobian information from RBFNN. Hence, it has strong adaptability to the variation of the system operating condition. The effectiveness of the proposed controller is tested on a two-machine five-bus power...... system and a four-machine two-area power system under different operating conditions in comparison with the lead-lag damping controller tuned by evolutionary algorithm (EA). Simulation results show that the proposed damping controller achieves good robust performance for damping the low frequency......In this paper, a nonlinear adaptive damping controller based on radial basis function neural network (RBFNN), which can infinitely approximate to nonlinear system, is proposed for thyristor controlled series capacitor (TCSC). The proposed TCSC adaptive damping controller can not only have...

  15. The 3 major types of innate and adaptive cell-mediated effector immunity.

    Science.gov (United States)

    Annunziato, Francesco; Romagnani, Chiara; Romagnani, Sergio

    2015-03-01

    The immune system has tailored its effector functions to optimally respond to distinct species of microbes. Based on emerging knowledge on the different effector T-cell and innate lymphoid cell (ILC) lineages, it is clear that the innate and adaptive immune systems converge into 3 major kinds of cell-mediated effector immunity, which we propose to categorize as type 1, type 2, and type 3. Type 1 immunity consists of T-bet(+) IFN-γ-producing group 1 ILCs (ILC1 and natural killer cells), CD8(+) cytotoxic T cells (TC1), and CD4(+) TH1 cells, which protect against intracellular microbes through activation of mononuclear phagocytes. Type 2 immunity consists of GATA-3(+) ILC2s, TC2 cells, and TH2 cells producing IL-4, IL-5, and IL-13, which induce mast cell, basophil, and eosinophil activation, as well as IgE antibody production, thus protecting against helminthes and venoms. Type 3 immunity is mediated by retinoic acid-related orphan receptor γt(+) ILC3s, TC17 cells, and TH17 cells producing IL-17, IL-22, or both, which activate mononuclear phagocytes but also recruit neutrophils and induce epithelial antimicrobial responses, thus protecting against extracellular bacteria and fungi. On the other hand, type 1 and 3 immunity mediate autoimmune diseases, whereas type 2 responses can cause allergic diseases. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Vorinostat enhances the cisplatin-mediated anticancer effects in small cell lung cancer cells.

    Science.gov (United States)

    Pan, Chun-Hao; Chang, Ying-Fang; Lee, Ming-Shuo; Wen, B-Chen; Ko, Jen-Chung; Liang, Sheng-Kai; Liang, Mei-Chih

    2016-11-07

    Vorinostat, a histone deacetylase (HDAC) inhibitor, is a promising agent for cancer therapy. Combining vorinostat with cisplatin may relax the chromatin structure and facilitate the accessibility of cisplatin, thus enhancing its cytotoxicity. Studies have not yet investigated the effects of the combination of vorinostat and cisplatin on small cell lung cancer (SCLC). We first assessed the efficacy of vorinostat with etoposide/cisplatin (EP; triple combination) and then investigated the effects of cotreatment with vorinostat and cisplatin on H209 and H146 SCLC cell lines. The anticancer effects of various combinations were determined in terms of cell viability, apoptosis, cell cycle distribution, and vorinostat-regulated proteins. We also evaluated the efficacy of vorinostat/cisplatin combination in H209 xenograft nude mice. Our data revealed that the triple combination engendered a significant reduction of cell viability and high apoptotic cell death. In addition, vorinostat combined with cisplatin enhanced cell growth inhibition, induced apoptosis, and promoted cell cycle arrest. We observed that the acetylation levels of histone H3 and α-tubulin were higher in combination treatments than in vorinostat treatment alone. Moreover, vorinostat reduced the expression of thymidylate synthase (TS), and TS remained inhibited after cotreament with cisplatin. Furthermore, an in vivo study revealed that the combination of vorinostat and cisplatin significantly inhibited tumor growth in xenograft nude mice (tumor growth inhibition T/C% = 20.5 %). Combined treatments with vorinostat promote the cytotoxicity of cisplatin and induce the expression of vorinostat-regulated acetyl proteins, eventually enhancing antitumor effects in SCLC cell lines. Triple combinations with a low dosage of cisplatin demonstrate similar therapeutic effects. Such triple combinations, if applied clinically, may reduce the undesired adverse effects of cisplatin. The effects of the combination of

  17. Role and contribution of pulmonary CD103+ dendritic cells in the adaptive immune response to Mycobacterium tuberculosis.

    Science.gov (United States)

    Koh, Vanessa Hui Qi; Ng, See Liang; Ang, Michelle Lay Teng; Lin, Wenwei; Ruedl, Christiane; Alonso, Sylvie

    2017-01-01

    Despite international control programmes, the global burden of tuberculosis remains enormous. Efforts to discover novel drugs have largely focused on targeting the bacterium directly. Alternatively, manipulating the host immune response may represent a valuable approach to enhance immunological clearance of the bacilli, but necessitates a deeper understanding of the immune mechanisms associated with protection against Mycobacterium tuberculosis infection. Here, we examined the various dendritic cells (DC) subsets present in the lung and draining lymph nodes (LN) from mice intra-tracheally infected with M. tuberculosis. We showed that although limited in number, pulmonary CD103 + DCs appeared to be involved in the initial transport of mycobacteria to the draining mediastinal LN and subsequent activation of T cells. Using CLEC9A-DTR transgenic mice enabling the inducible depletion of CD103 + DCs, we established that this DC subset contributes to the control of mycobacterial burden and plays a role in the early activation of T cells, in particular CD8 + T cells. Our findings thus support a previously unidentified role for pulmonary CD103 + DCs in the rapid mobilization of mycobacteria from the lungs to the draining LN soon after exposure to M. tuberculosis, which is a critical step for the development of the host adaptive immune response. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation

    Directory of Open Access Journals (Sweden)

    Nicholas Jones

    2017-11-01

    Full Text Available Linking immunometabolic adaptation to T-cell function provides insight for the development of new therapeutic approaches in multiple disease settings. T-cell activation and downstream effector functions of CD4+ and CD8+ T-cells are controlled by the strength of interaction between the T-cell receptor (TCR and peptides presented by human leukocyte antigens (pHLA. The role of TCR–pHLA interactions in modulating T-cell metabolism is unknown. Here, for the first time, we explore the relative contributions of the main metabolic pathways to functional responses in human CD4+ and CD8+ T-cells. Increased expression of hexokinase II accompanied by higher basal glycolysis is demonstrated in CD4+ T-cells; cytokine production in CD8+ T-cells is more reliant on oxidative phosphorylation. Using antigen-specific CD4+ and CD8+ T-cell clones and altered peptide ligands, we demonstrate that binding affinity tunes the underlying metabolic shift. Overall, this study provides important new insight into how metabolic pathways are controlled during antigen-specific activation of human T-cells.

  19. Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis

    DEFF Research Database (Denmark)

    Lauenborg, Britt; Kopp, Katharina; Krejsgaard, Thorbjørn

    2010-01-01

    is associated with serine/threonine kinases and phosphatases and modulates the extracellular signal-regulated kinase pathway suggesting a role in the regulation of cellular growth. Here we provide evidence of a constitutive expression of PDCD10 in malignant T cells and cell lines from peripheral blood......, whereas an activator of Jak3 and NF-¿B, interleukin-2 (IL-2), enhances PDCD10 expression. Functional data show that PDCD10 depletion by small interfering RNA induces apoptosis and decreases proliferation of the sensitive cells. To our knowledge, these data provide the first functional link between PDCD10...

  20. Content-adaptive Image Enhancement, Based on Sky and Grass Segmentation

    NARCIS (Netherlands)

    Zafarifar, B.; With, de P.H.N.

    2009-01-01

    Current TV image enhancement functions employ globally controlled settings. A more flexible system can be achieved if the global control is extended to incorporate semantic-level image content information. In this paper, we present a system that extends existing TV image enhancement functions with

  1. Enhanced SCAP glycosylation by inflammation induces macrophage foam cell formation.

    Directory of Open Access Journals (Sweden)

    Chao Zhou

    Full Text Available Inflammatory stress promotes foam cell formation by disrupting LDL receptor feedback regulation in macrophages. Sterol Regulatory Element Binding Proteins (SREBPs Cleavage-Activating Protein (SCAP glycosylation plays crucial roles in regulating LDL receptor and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR feedback regulation. The present study was to investigate if inflammatory stress disrupts LDL receptor and HMGCoAR feedback regulation by affecting SCAP glycosylation in THP-1 macrophages. Intracellular cholesterol content was assessed by Oil Red O staining and quantitative assay. The expression of molecules controlling cholesterol homeostasis was examined using real-time quantitative RT-PCR and Western blotting. The translocation of SCAP from the endoplasmic reticulum (ER to the Golgi was detected by confocal microscopy. We demonstrated that exposure to inflammatory cytokines increased lipid accumulation in THP-1 macrophages, accompanying with an increased SCAP expression even in the presence of a high concentration of LDL. These inflammatory cytokines also prolonged the half-life of SCAP by enhancing glycosylation of SCAP due to the elevated expression of the Golgi mannosidase II. This may enhance translocation and recycling of SCAP between the ER and the Golgi, escorting more SREBP2 from the ER to the Golgi for activation by proteolytic cleavages as evidenced by an increased N-terminal of SREBP2 (active form. As a consequence, the LDL receptor and HMGCoAR expression were up-regulated. Interestingly, these effects could be blocked by inhibitors of Golgi mannosidases. Our results indicated that inflammation increased native LDL uptake and endogenous cholesterol de novo synthesis, thereby causing foam cell formation via increasing transcription and protein glycosylation of SCAP in macrophages. These data imply that inhibitors of Golgi processing enzymes might have a potential vascular-protective role in prevention of atherosclerotic foam

  2. Mesenchymal Stem Cells Enhance Allogeneic Islet Engraftment in Nonhuman Primates

    Science.gov (United States)

    Berman, Dora M.; Willman, Melissa A.; Han, Dongmei; Kleiner, Gary; Kenyon, Norman M.; Cabrera, Over; Karl, Julie A.; Wiseman, Roger W.; O'Connor, David H.; Bartholomew, Amelia M.; Kenyon, Norma S.

    2010-01-01

    OBJECTIVE To test the graft-promoting effects of mesenchymal stem cells (MSCs) in a cynomolgus monkey model of islet/bone marrow transplantation. RESEARCH DESIGN AND METHODS Cynomolgus MSCs were obtained from iliac crest aspirate and characterized through passage 11 for phenotype, gene expression, differentiation potential, and karyotype. Allogeneic donor MSCs were cotransplanted intraportally with islets on postoperative day (POD) 0 and intravenously with donor marrow on PODs 5 and 11. Recipients were followed for stabilization of blood glucose levels, reduction of exogenous insulin requirement (EIR), C-peptide levels, changes in peripheral blood T regulatory cells, and chimerism. Destabilization of glycemia and increases in EIR were used as signs of rejection; additional intravenous MSCs were administered to test the effect on reversal of rejection. RESULTS MSC phenotype and a normal karyotype were observed through passage 11. IL-6, IL-10, vascular endothelial growth factor, TGF-β, hepatocyte growth factor, and galectin-1 gene expression levels varied among donors. MSC treatment significantly enhanced islet engraftment and function at 1 month posttransplant (n = 8), as compared with animals that received islets without MSCs (n = 3). Additional infusions of donor or third-party MSCs resulted in reversal of rejection episodes and prolongation of islet function in two animals. Stable islet allograft function was associated with increased numbers of regulatory T-cells in peripheral blood. CONCLUSIONS MSCs may provide an important approach for enhancement of islet engraftment, thereby decreasing the numbers of islets needed to achieve insulin independence. Furthermore, MSCs may serve as a new, safe, and effective antirejection therapy. PMID:20622174

  3. Osteopontin-enhanced hepatic metastasis of colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Jianjin Huang

    Full Text Available Liver metastasis is a major cause of mortality from colorectal cancer (CRC. However, mechanisms underlying this process are largely unknown. Osteopontin (OPN is a secreted phosphorylated glycoprotein that is involved in tumor migration and metastasis. The role of OPN in cancer is currently unclear. In this study, OPN mRNA was examined in tissues from CRC, adjacent normal mucosa, and liver metastatic lesions using quantitative real-time PCR analysis. The protein expression of OPN and its receptors (integrin αv and CD44 v6 was detected by using an immunohistochemical (IHC method. The role of OPN in liver metastasis was studied in established colon cancer Colo-205 and SW-480 cell lines transfected with sense- or antisense-OPN eukaryotic expression plasmids by flow cytometry and cell adhesion assay. Fluorescence redistribution after photobleaching (FRAP was used to study gap functional intercellular communication (GJIC among OPN-transfected cells. It was found that OPN was highly expressed in metastatic hepatic lesions from CRC compared to primary CRC tissue and adjacent normal mucosa. The expression of OPN mRNA in tumor tissues was significantly related with the CRC stages. OPN expression was also detected in normal hepatocytes surrounding CRC metastatic lesions. Two known receptors of OPN, integrin αv and CD44v6 proteins, were strongly expressed in hepatocytes from normal liver. CRC cells with forced OPN expression exhibited increased heterotypic adhesion with endothelial cells and weakened intercellular communication. OPN plays a significant role in CRC metastasis to liver through interaction with its receptors in hepatocytes, decreased homotypic adhesion, and enhanced heterotypic adhesion.

  4. Adaptive Multiscale Noise Control Enhanced Stochastic Resonance Method Based on Modified EEMD with Its Application in Bearing Fault Diagnosis

    Directory of Open Access Journals (Sweden)

    Jimeng Li

    2016-01-01

    Full Text Available The structure of mechanical equipment becomes increasingly complex, and tough environments under which it works often make bearings and gears subject to failure. However, effective extraction of useful feature information submerged in strong noise that is indicative of structural defects has remained a major challenge. Therefore, an adaptive multiscale noise control enhanced stochastic resonance (SR method based on modified ensemble empirical mode decomposition (EEMD for mechanical fault diagnosis is proposed in the paper. According to the oscillation characteristics of signal itself, the algorithm of modified EEMD can adaptively decompose the fault signals into different scales and it reduces the decomposition levels to improve calculation efficiency of the proposed method. Through filter processing with the constructed filters, the orthogonality of adjacent intrinsic mode functions (IMFs can be improved, which is conducive to enhancing the extraction of weak features from strong noise. The constructed signal obtained by using IMFs is inputted into the SR system, and the noise control parameter of different scales is optimized and selected with the help of the genetic algorithm, thus achieving the enhancement extraction of weak features. Finally, simulation experiments and engineering application of bearing fault diagnosis demonstrate the effectiveness and feasibility of the proposed method.

  5. Spatio-Temporal Super-Resolution Reconstruction of Remote-Sensing Images Based on Adaptive Multi-Scale Detail Enhancement.

    Science.gov (United States)

    Zhu, Hong; Tang, Xinming; Xie, Junfeng; Song, Weidong; Mo, Fan; Gao, Xiaoming

    2018-02-07

    There are many problems in existing reconstruction-based super-resolution algorithms, such as the lack of texture-feature representation and of high-frequency details. Multi-scale detail enhancement can produce more texture information and high-frequency information. Therefore, super-resolution reconstruction of remote-sensing images based on adaptive multi-scale detail enhancement (AMDE-SR) is proposed in this paper. First, the information entropy of each remote-sensing image is calculated, and the image with the maximum entropy value is regarded as the reference image. Subsequently, spatio-temporal remote-sensing images are processed using phase normalization, which is to reduce the time phase difference of image data and enhance the complementarity of information. The multi-scale image information is then decomposed using the L ₀ gradient minimization model, and the non-redundant information is processed by difference calculation and expanding non-redundant layers and the redundant layer by the iterative back-projection (IBP) technique. The different-scale non-redundant information is adaptive-weighted and fused using cross-entropy. Finally, a nonlinear texture-detail-enhancement function is built to improve the scope of small details, and the peak signal-to-noise ratio (PSNR) is used as an iterative constraint. Ultimately, high-resolution remote-sensing images with abundant texture information are obtained by iterative optimization. Real results show an average gain in entropy of up to 0.42 dB for an up-scaling of 2 and a significant promotion gain in enhancement measure evaluation for an up-scaling of 2. The experimental results show that the performance of the AMED-SR method is better than existing super-resolution reconstruction methods in terms of visual and accuracy improvements.

  6. Spatio-Temporal Super-Resolution Reconstruction of Remote-Sensing Images Based on Adaptive Multi-Scale Detail Enhancement

    Science.gov (United States)

    Zhu, Hong; Tang, Xinming; Xie, Junfeng; Song, Weidong; Mo, Fan; Gao, Xiaoming

    2018-01-01

    There are many problems in existing reconstruction-based super-resolution algorithms, such as the lack of texture-feature representation and of high-frequency details. Multi-scale detail enhancement can produce more texture information and high-frequency information. Therefore, super-resolution reconstruction of remote-sensing images based on adaptive multi-scale detail enhancement (AMDE-SR) is proposed in this paper. First, the information entropy of each remote-sensing image is calculated, and the image with the maximum entropy value is regarded as the reference image. Subsequently, spatio-temporal remote-sensing images are processed using phase normalization, which is to reduce the time phase difference of image data and enhance the complementarity of information. The multi-scale image information is then decomposed using the L0 gradient minimization model, and the non-redundant information is processed by difference calculation and expanding non-redundant layers and the redundant layer by the iterative back-projection (IBP) technique. The different-scale non-redundant information is adaptive-weighted and fused using cross-entropy. Finally, a nonlinear texture-detail-enhancement function is built to improve the scope of small details, and the peak signal-to-noise ratio (PSNR) is used as an iterative constraint. Ultimately, high-resolution remote-sensing images with abundant texture information are obtained by iterative optimization. Real results show an average gain in entropy of up to 0.42 dB for an up-scaling of 2 and a significant promotion gain in enhancement measure evaluation for an up-scaling of 2. The experimental results show that the performance of the AMED-SR method is better than existing super-resolution reconstruction methods in terms of visual and accuracy improvements. PMID:29414893

  7. Evidence that pulsed electric field treatment enhances the cell wall porosity of yeast cells.

    Science.gov (United States)

    Ganeva, Valentina; Galutzov, Bojidar; Teissie, Justin

    2014-02-01

    The application of rectangular electric pulses, with 0.1-2 ms duration and field intensity of 2.5-4.5 kV/cm, to yeast suspension mediates liberation of cytoplasmic proteins without cell lysis. The aim of this study was to evaluate the effect of pulsed electric field with similar parameters on cell wall porosity of different yeast species. We found that electrically treated cells become more susceptible to lyticase digestion. In dependence on the strain and the electrical conditions, cell lysis was obtained at 2-8 times lower enzyme concentration in comparison with control untreated cells. The increase of the maximal lysis rate was between two and nine times. Furthermore, when applied at low concentration (1 U/ml), the lyticase enhanced the rate of protein liberation from electropermeabilized cells without provoking cell lysis. Significant differences in the cell surface of control and electrically treated cells were revealed by scanning electron microscopy. Data presented in this study allow us to conclude that electric field pulses provoke not only plasma membrane permeabilization, but also changes in the cell wall structure, leading to increased wall porosity.

  8. Enhancing Students' Confidence in Employability Skills through the Practice of "Recall, Adapt and Apply"

    Science.gov (United States)

    Sinclair, Alison J.

    2017-01-01

    The ability to apply prior knowledge to new challenges is a skill that is highly valued by employers, but the confidence to achieve this does not come naturally to all students. An essential step to becoming an independent researcher requires a transition between simply following a fail-safe set of instructions to being able to adapt a known…

  9. Enhancing Perception with Tactile Object Recognition in Adaptive Grippers for Human–Robot Interaction

    Directory of Open Access Journals (Sweden)

    Juan M. Gandarias

    2018-02-01

    Full Text Available The use of tactile perception can help first response robotic teams in disaster scenarios, where visibility conditions are often reduced due to the presence of dust, mud, or smoke, distinguishing human limbs from other objects with similar shapes. Here, the integration of the tactile sensor in adaptive grippers is evaluated, measuring the performance of an object recognition task based on deep convolutional neural networks (DCNNs using a flexible sensor mounted in adaptive grippers. A total of 15 classes with 50 tactile images each were trained, including human body parts and common environment objects, in semi-rigid and flexible adaptive grippers based on the fin ray effect. The classifier was compared against the rigid configuration and a support vector machine classifier (SVM. Finally, a two-level output network has been proposed to provide both object-type recognition and human/non-human classification. Sensors in adaptive grippers have a higher number of non-null tactels (up to 37% more, with a lower mean of pressure values (up to 72% less than when using a rigid sensor, with a softer grip, which is needed in physical human–robot interaction (pHRI. A semi-rigid implementation with 95.13% object recognition rate was chosen, even though the human/non-human classification had better results (98.78% with a rigid sensor.

  10. A Feedback Control Strategy for Enhancing Item Selection Efficiency in Computerized Adaptive Testing

    Science.gov (United States)

    Weissman, Alexander

    2006-01-01

    A computerized adaptive test (CAT) may be modeled as a closed-loop system, where item selection is influenced by trait level ([theta]) estimation and vice versa. When discrepancies exist between an examinee's estimated and true [theta] levels, nonoptimal item selection is a likely result. Nevertheless, examinee response behavior consistent with…

  11. ERP Human Enhancement Progress Report : Use case and computational model for adaptive maritime automation

    NARCIS (Netherlands)

    Kleij, R. van der; Broek, J. van den; Brake, G.M. te; Rypkema, J.A.; Schilder, C.M.C.

    2015-01-01

    Automation is often applied in order to increase the cost-effectiveness, reliability and safety of maritime ship and offshore operations. Automation of operator tasks, has not, however, eliminated human error so much as created opportunities for new kinds of error. The ambition of the Adaptive

  12. Enhancing Perception with Tactile Object Recognition in Adaptive Grippers for Human-Robot Interaction.

    Science.gov (United States)

    Gandarias, Juan M; Gómez-de-Gabriel, Jesús M; García-Cerezo, Alfonso J

    2018-02-26

    The use of tactile perception can help first response robotic teams in disaster scenarios, where visibility conditions are often reduced due to the presence of dust, mud, or smoke, distinguishing human limbs from other objects with similar shapes. Here, the integration of the tactile sensor in adaptive grippers is evaluated, measuring the performance of an object recognition task based on deep convolutional neural networks (DCNNs) using a flexible sensor mounted in adaptive grippers. A total of 15 classes with 50 tactile images each were trained, including human body parts and common environment objects, in semi-rigid and flexible adaptive grippers based on the fin ray effect. The classifier was compared against the rigid configuration and a support vector machine classifier (SVM). Finally, a two-level output network has been proposed to provide both object-type recognition and human/non-human classification. Sensors in adaptive grippers have a higher number of non-null tactels (up to 37% more), with a lower mean of pressure values (up to 72% less) than when using a rigid sensor, with a softer grip, which is needed in physical human-robot interaction (pHRI). A semi-rigid implementation with 95.13% object recognition rate was chosen, even though the human/non-human classification had better results (98.78%) with a rigid sensor.

  13. Low-power, enhanced-gain adaptive-biasing-based Operational Transconductance Amplifiers

    DEFF Research Database (Denmark)

    Moradi, Farshad

    A symmetrical PMOS OTA (Operational Transconductance Amplifier) is used to build an advanced rail-to-rail amplifier with improved DC-gain and reduced power consumption. By using the adaptive biasing circuit for two differential inputs, a low stand-by current can be achieved, reducing power...

  14. Mitochondrial Respiration in Insulin-Producing β-Cells: General Characteristics and Adaptive Effects of Hypoxia.

    Science.gov (United States)

    Hals, Ingrid K; Bruerberg, Simon Gustafson; Ma, Zuheng; Scholz, Hanne; Björklund, Anneli; Grill, Valdemar

    2015-01-01

    To provide novel insights on mitochondrial respiration in β-cells and the adaptive effects of hypoxia. Insulin-producing INS-1 832/13 cells were exposed to 18 hours of hypoxia followed by 20-22 hours re-oxygenation. Mitochondrial respiration was measured by high-resolution respirometry in both intact and permeabilized cells, in the latter after establishing three functional substrate-uncoupler-inhibitor titration (SUIT) protocols. Concomitant measurements included proteins of mitochondrial complexes (Western blotting), ATP and insulin secretion. Intact cells exhibited a high degree of intrinsic uncoupling, comprising about 50% of oxygen consumption in the basal respiratory state. Hypoxia followed by re-oxygenation increased maximal overall respiration. Exploratory experiments in peremabilized cells could not show induction of respiration by malate or pyruvate as reducing substrates, thus glutamate and succinate were used as mitochondrial substrates in SUIT protocols. Permeabilized cells displayed a high capacity for oxidative phosphorylation for both complex I- and II-linked substrates in relation to maximum capacity of electron transfer. Previous hypoxia decreased phosphorylation control of complex I-linked respiration, but not in complex II-linked respiration. Coupling control ratios showed increased coupling efficiency for both complex I- and II-linked substrates in hypoxia-exposed cells. Respiratory rates overall were increased. Also previous hypoxia increased proteins of mitochondrial complexes I and II (Western blotting) in INS-1 cells as well as in rat and human islets. Mitochondrial effects were accompanied by unchanged levels of ATP, increased basal and preserved glucose-induced insulin secretion. Exposure of INS-1 832/13 cells to hypoxia, followed by a re-oxygenation period increases substrate-stimulated respiratory capacity and coupling efficiency. Such effects are accompanied by up-regulation of mitochondrial complexes also in pancreatic islets

  15. Cell penetrating peptide-modified poly(lactic-co-glycolic acid) nanoparticles with enhanced cell internalization.

    Science.gov (United States)

    Steinbach, Jill M; Seo, Young-Eun; Saltzman, W Mark

    2016-01-01

    The surface modification of nanoparticles (NPs) can enhance the intracellular delivery of drugs, proteins, and genetic agents. Here we studied the effect of different surface ligands, including cell penetrating peptides (CPPs), on the cell binding and internalization of poly(lactic-co-glycolic) (PLGA) NPs. Relative to unmodified NPs, we observed that surface-modified NPs greatly enhanced cell internalization. Using one CPP, MPG (unabbreviated notation), that achieved the highest degree of internalization at both low and high surface modification densities, we evaluated the effect of two different NP surface chemistries on cell internalization. After 2h, avidin-MPG NPs enhanced cellular internalization by 5 to 26-fold relative to DSPE-MPG NP formulations. Yet, despite a 5-fold increase in MPG density on DSPE compared to Avidin NPs, both formulations resulted in similar internalization levels (48 and 64-fold, respectively) after 24h. Regardless of surface modification, all NPs were internalized through an energy-dependent, clathrin-mediated process, and became dispersed throughout the cell. Overall both Avidin- and DSPE-CPP modified NPs significantly increased internalization and offer promising delivery options for applications in which internalization presents challenges to efficacious delivery. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. Adaptive changes in NAD+ metabolism in ultraviolet light-irradiated murine lymphoma cells

    International Nuclear Information System (INIS)

    Kleczkowska, H.E.; Szumiel, I.; Althaus, F.R.

    1990-01-01

    We have determined the ability of UV254nm-irradiated murine lymphoma cells to adapt their NAD+ metabolism to the increased NAD+ consumption for the poly ADP-ribosylation of chromatin proteins. Two murine lymphoma sublines with differential UV-sensitivity and poly(ADP-ribose) turnover were used as a model system. The first subline, designated LY-R is UV254nm-sensitive and tumorigenic in DBA/2 mice. The second subline, LY-S is UV254nm-resistant and nontumorigenic. Following treatment of these cells with 2 mM benzamide, an inhibitor of the NAD(+)-utilizing enzyme poly(ADP-ribose) polymerase, NAD+ levels slowly increased up to about 160% of control levels after 3 hours. When benzamide was added to these cultures 20 min after UV254nm irradiation, a dramatic transient increase of NAD+ levels was observed within 4 min in LY-R cells and more moderately in LY-S cells. At later times after UV254nm irradiation, the NAD+ levels increased in both sublines reaching up to 200% of the concentrations prior to benzamide treatment. These results demonstrate an adaptative response of NAD+ metabolism to UV254nm irradiation. In parallel, we observed a differential repartitioning of ADP-ribosyl residues between the NAD+ and poly(ADP-ribose) pools of LY-R and LY-S cells that correlates with the differential UV sensitivity of these cells

  17. Adaptive response to ionizing radiation in normal human skin fibroblasts. Enhancement of DNA repair rate and modulation of gene expression

    International Nuclear Information System (INIS)

    Toledo, S.M. de; Mitchel, R.E.J.; Azzam, E.; Ottawa Univ., ON; Raaphorst, G.P.

    1994-01-01

    Low doses and dose rates of ionizing radiation enhance the rate of DNA repair in human fibroblasts and protect the cells against radiation-induced micronucleus formation. Chronic exposures reduce the mRNA levels of the genes topoisomerase II and FACC-1 (Fanconi's anemia, group C). (authors). 11 refs., 1 tab., 2 figs

  18. Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia.

    Science.gov (United States)

    Reeves, Daniel B; Peterson, Christopher W; Kiem, Hans-Peter; Schiffer, Joshua T

    2017-07-01

    Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the "Berlin patient" remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact

  19. Delayed-rectifier K channels contribute to contrast adaptation in mammalian retinal ganglion cells.

    Science.gov (United States)

    Weick, Michael; Demb, Jonathan B

    2011-07-14

    Retinal ganglion cells adapt by reducing their sensitivity during periods of high contrast. Contrast adaptation in the firing response depends on both presynaptic and intrinsic mechanisms. Here, we investigated intrinsic mechanisms for contrast adaptation in OFF Alpha ganglion cells in the in vitro guinea pig retina. Using either visual stimulation or current injection, we show that brief depolarization evoked spiking and suppressed firing during subsequent depolarization. The suppression could be explained by Na channel inactivation, as shown in salamander cells. However, brief hyperpolarization in the physiological range (5-10 mV) also suppressed firing during subsequent depolarization. This suppression was selectively sensitive to blockers of delayed-rectifier K channels (K(DR)). In somatic membrane patches, we observed tetraethylammonium-sensitive K(DR) currents that activated near -25 mV. Recovery from inactivation occurred at potentials hyperpolarized to V(rest). Brief periods of hyperpolarization apparently remove K(DR) inactivation and thereby increase the channel pool available to suppress excitability during subsequent depolarization. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Sliding mode disturbance observer-enhanced adaptive control for the air-breathing hypersonic flight vehicle

    Science.gov (United States)

    An, Hao; Wang, Changhong; Fidan, Baris

    2017-10-01

    This paper presents a backstepping procedure to design an adaptive controller for the air-breathing hypersonic flight vehicle (AHFV) subject to external disturbances and actuator saturations. In each step, a sliding mode exact disturbance observer (SMEDO) is exploited to exactly estimate the lumped disturbance in finite time. Specific dynamics are introduced to handle the possible actuator saturations. Based on SMEDO and introduced dynamics, an adaptive control law is designed, along with the consideration on ;explosion of complexity; in backstepping design. The developed controller is equipped with fast disturbance rejection and great capability to accommodate the saturated actuators, which also lead to a wider application scope. A simulation study is provided to show the effectiveness and superiority of the proposed controller.

  1. Optical enhancement effects of plasmonic nanostructures on organic photovoltaic cells

    KAUST Repository

    Park, Hui Joon

    2015-04-01

    © 2015 Hui Joon Park and L. Jay Guo. Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. All rights reserved. In this article, the optical enhancement effects of plasmonic nanostructures on OPV cells were reviewed as an effective way to resolve the mismatch problems between the short exciton diffusion length in organic semiconductors (around 10 nm) and the large thickness required to fully absorb sunlight (e.g. hundreds of nanometers). Especially, the performances of OPVs with plasmonic nanoparticles in photoactive and buffer layers and with periodic nanostructures were investigated. Furthermore, nanoimprint lithography-based nanofabrication processes that can easily control the dimension and uniformity of structures for large-area and uniform plasmonic nanostructures were demonstrated.

  2. Experimental Evaluation of Interference Suppression Receivers and Rank Adaptation in 5G Small Cells

    DEFF Research Database (Denmark)

    Assefa, Dereje; Berardinelli, Gilberto; Catania, Davide

    2015-01-01

    Advanced receivers are a key component of the 5th Generation (5G) ultra-dense small cells concept given their capability of efficiently dealing with the ever-increasing problem of inter-cell interference. In this paper, we evaluate the potential of interference suppression receivers in real network...... the Interference Rejection Combining (IRC) and Successive Interference Cancellation (SIC) receivers and different rank adaptation approaches. Each node in our software defined radio (SDR) testbed features a 22 MIMO transceiver built with the USRP N200 hardware by Ettus Research. Our experimental results confirm...

  3. Acacetin enhances the therapeutic efficacy of doxorubicin in non-small-cell lung carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Reenu Punia

    doxorubicin influx and efflux was mediated through downregulation of MDR1 treansporter in NSCLC cells.These findings suggested that acacetin augments the cytotoxicity of doxorubicin at lower concentrations in lung cancer cells. Their combination leads to more retention of doxorubicin in the cells by modulating drug trasporter and thus enhances its therapeutic potential.

  4. Muscle adaptations and performance enhancements of soccer training for untrained men

    DEFF Research Database (Denmark)

    Krustrup, Peter; Christensen, Jesper F.; Randers, Morten Bredsgaard

    2010-01-01

    We examined the physical demands of small-sided soccer games in untrained middle-age males and muscle adaptations and performance effects over 12 weeks of recreational soccer training in comparison with continuous running. Thirty-eight healthy subjects (20-43 years) were randomized into a soccer....... Blood lactate during running at 11 km/h was lowered (p soccer organized as small-sided games stimulates both aerobic and anaerobic...

  5. Coupling internal cerebellar models enhances online adaptation and supports offline consolidation in sensorimotor tasks

    OpenAIRE

    Passot , Jean-Baptiste; Luque , Niceto R.; Arleo , Angelo

    2013-01-01

    International audience; The cerebellum is thought to mediate sensorimotor adaptation through the acquisition of internal models of the body-environment interaction. These representations can be of two types, identified as forward and inverse models. The first predicts the sensory consequences of actions, while the second provides the correct commands to achieve desired state transitions. In this paper, we propose a composite architecture consisting of multiple cerebellar internal models to ac...

  6. Enhancing HumanAgent Teaming with Individualized, Adaptive Technologies: A Discussion of Critical Scientific Questions

    Science.gov (United States)

    2018-05-04

    reliability of information available is often unknown. What mechanisms must be in place to account for and adapt to the fluid nature of information ...reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching...existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection information . Send comments regarding

  7. Adaptive SLICE method: an enhanced method to determine nonlinear dynamic respiratory system mechanics

    International Nuclear Information System (INIS)

    Zhao, Zhanqi; Möller, Knut; Guttmann, Josef

    2012-01-01

    The objective of this paper is to introduce and evaluate the adaptive SLICE method (ASM) for continuous determination of intratidal nonlinear dynamic compliance and resistance. The tidal volume is subdivided into a series of volume intervals called slices. For each slice, one compliance and one resistance are calculated by applying a least-squares-fit method. The volume window (width) covered by each slice is determined based on the confidence interval of the parameter estimation. The method was compared to the original SLICE method and evaluated using simulation and animal data. The ASM was also challenged with separate analysis of dynamic compliance during inspiration. If the signal-to-noise ratio (SNR) in the respiratory data decreased from +∞ to 10 dB, the relative errors of compliance increased from 0.1% to 22% for the ASM and from 0.2% to 227% for the SLICE method. Fewer differences were found in resistance. When the SNR was larger than 40 dB, the ASM delivered over 40 parameter estimates (42.2 ± 1.3). When analyzing the compliance during inspiration separately, the estimates calculated with the ASM were more stable. The adaptive determination of slice bounds results in consistent and reliable parameter values. Online analysis of nonlinear respiratory mechanics will profit from such an adaptive selection of interval size. (paper)

  8. Microfluidic Adaptation of Density-Gradient Centrifugation for Isolation of Particles and Cells

    Directory of Open Access Journals (Sweden)

    Yuxi Sun

    2017-08-01

    Full Text Available Density-gradient centrifugation is a label-free approach that has been extensively used for cell separations. Though elegant, this process is time-consuming (>30 min, subjects cells to high levels of stress (>350 g and relies on user skill to enable fractionation of cells that layer as a narrow band between the density-gradient medium and platelet-rich plasma. We hypothesized that microfluidic adaptation of this technique could transform this process into a rapid fractionation approach where samples are separated in a continuous fashion while being exposed to lower levels of stress (<100 g for shorter durations of time (<3 min. To demonstrate proof-of-concept, we designed a microfluidic density-gradient centrifugation device and constructed a setup to introduce samples and medium like Ficoll in a continuous, pump-less fashion where cells and particles can be exposed to centrifugal force and separated via different outlets. Proof-of-concept studies using binary mixtures of low-density polystyrene beads (1.02 g/cm3 and high-density silicon dioxide beads (2.2 g/cm3 with Ficoll–Paque (1.06 g/cm3 show that separation is indeed feasible with >99% separation efficiency suggesting that this approach can be further adapted for separation of cells.

  9. Reversible adaptive plasticity: A mechanism for neuroblastoma cell heterogeneity and chemo-resistance

    Directory of Open Access Journals (Sweden)

    Lina eChakrabarti

    2012-08-01

    Full Text Available We describe a novel form of tumor cell plasticity characterized by reversible adaptive plasticity in murine and human neuroblastoma. Two cellular phenotypes were defined by their ability to exhibit adhered, anchorage dependent (AD or sphere forming, anchorage independent (AI growth. The tumor cells could transition back and forth between the two phenotypes and the transition was dependent on the culture conditions. Both cell phenotypes exhibited stem-like features such as expression of nestin, self-renewal capacity and mesenchymal differentiation potential. The AI tumorspheres were found to be more resistant to chemotherapy and proliferated slower in vitro compared to the AD cells. Identification of specific molecular markers like MAP2, β-catenin and PDGFRβ enabled us to characterize and observe both phenotypes in established mouse tumors. Irrespective of the phenotype originally implanted in mice, tumors grown in vivo show phenotypic heterogeneity in molecular marker signatures and are indistinguishable in growth or histologic appearance. Similar molecular marker heterogeneity was demonstrated in primary human tumor specimens. Chemotherapy or growth factor receptor inhibition slowed tumor growth in mice and promoted initial loss of AD or AI heterogeneity, respectively. Simultaneous targeting of both phenotypes led to further tumor growth delay with emergence of new unique phenotypes. Our results demonstrate that neuroblastoma cells are plastic, dynamic and may optimize their ability to survive by changing their phenotype. Phenotypic switching appears to be an adaptive mechanism to unfavorable selection pressure and could explain the phenotypic and functional heterogeneity of neuroblastoma.

  10. Reversible Adaptive Plasticity: A Mechanism for Neuroblastoma Cell Heterogeneity and Chemo-Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Chakrabarti, Lina; Abou-Antoun, Thamara; Vukmanovic, Stanislav; Sandler, Anthony D., E-mail: asandler@childrensnational.org [The Joseph E. Robert Center for Surgical Care, Children’s National Medical Center, Washington, DC (United States); The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Medical Center, Washington, DC (United States)

    2012-08-02

    We describe a novel form of tumor cell plasticity characterized by reversible adaptive plasticity in murine and human neuroblastoma. Two cellular phenotypes were defined by their ability to exhibit adhered, anchorage dependent (AD) or sphere forming, anchorage independent (AI) growth. The tumor cells could transition back and forth between the two phenotypes and the transition was dependent on the culture conditions. Both cell phenotypes exhibited stem-like features such as expression of nestin, self-renewal capacity, and mesenchymal differentiation potential. The AI tumorspheres were found to be more resistant to chemotherapy and proliferated slower in vitro compared to the AD cells. Identification of specific molecular markers like MAP2, β-catenin, and PDGFRβ enabled us to characterize and observe both phenotypes in established mouse tumors. Irrespective of the phenotype originally implanted in mice, tumors grown in vivo show phenotypic heterogeneity in molecular marker signatures and are indistinguishable in growth or histologic appearance. Similar molecular marker heterogeneity was demonstrated in primary human tumor specimens. Chemotherapy or growth factor receptor inhibition slowed tumor growth in mice and promoted initial loss of AD or AI heterogeneity, respectively. Simultaneous targeting of both phenotypes led to further tumor growth delay with emergence of new unique phenotypes. Our results demonstrate that neuroblastoma cells are plastic, dynamic, and may optimize their ability to survive by changing their phenotype. Phenotypic switching appears to be an adaptive mechanism to unfavorable selection pressure and could explain the phenotypic and functional heterogeneity of neuroblastoma.

  11. An engineered approach to stem cell culture: automating the decision process for real-time adaptive subculture of stem cells.

    Directory of Open Access Journals (Sweden)

    Dai Fei Elmer Ker

    Full Text Available Current cell culture practices are dependent upon human operators and remain laborious and highly subjective, resulting in large variations and inconsistent outcomes, especially when using visual assessments of cell confluency to determine the appropriate time to subculture cells. Although efforts to automate cell culture with robotic systems are underway, the majority of such systems still require human intervention to determine when to subculture. Thus, it is necessary to accurately and objectively determine the appropriate time for cell passaging. Optimal stem cell culturing that maintains cell pluripotency while maximizing cell yields will be especially important for efficient, cost-effective stem cell-based therapies. Toward this goal we developed a real-time computer vision-based system that monitors the degree of cell confluency with a precision of 0.791±0.031 and recall of 0.559±0.043. The system consists of an automated phase-contrast time-lapse microscope and a server. Multiple dishes are sequentially imaged and the data is uploaded to the server that performs computer vision processing, predicts when cells will exceed a pre-defined threshold for optimal cell confluency, and provides a Web-based interface for remote cell culture monitoring. Human operators are also notified via text messaging and e-mail 4 hours prior to reaching this threshold and immediately upon reaching this threshold. This system was successfully used to direct the expansion of a paradigm stem cell population, C2C12 cells. Computer-directed and human-directed control subcultures required 3 serial cultures to achieve the theoretical target cell yield of 50 million C2C12 cells and showed no difference for myogenic and osteogenic differentiation. This automated vision-based system has potential as a tool toward adaptive real-time control of subculturing, cell culture optimization and quality assurance/quality control, and it could be integrated with current and

  12. Biomechanical signals guiding stem cell cartilage engineering: from molecular adaption to tissue functionality

    Directory of Open Access Journals (Sweden)

    Y Zhang

    2016-01-01

    Full Text Available In vivo cartilage is in a state of constant mechanical stimulation. It is therefore reasonable to deduce that mechanical forces play an important role in cartilage formation. Mechanical forces, such as compression, tension, and shear force, have been widely applied for cartilage engineering; however, relatively few review papers have summarized the influence of biomechanical signals on stem cell-based neo-cartilage formation and cartilage engineering in both molecular adaption and tissue functionality. In this review, we will discuss recent progress related to the influences of substrate elasticity on stem cell chondrogenic differentiation and elucidate the potential underlying mechanisms. Aside from active sensing and responding to the extracellular environment, stem cells also could respond to various external mechanical forces, which also influence their chondrogenic capacity; this topic will be updated along with associated signaling pathways. We expect that these different regimens of biomechanical signals can be utilized to boost stem cell-based cartilage engineering and regeneration.

  13. Use of the photovoltaic cells as fission fragment sensors and study of a preamplifier adapted to the cells

    International Nuclear Information System (INIS)

    Jin Yimeng.

    1989-04-01

    In the detection of heavy ions and fission fragments, the photovoltaic cells can take the place of traditional silicon surface barrier detectors, if we need a great number of detectors as in the case of 4π multidetector, and do not expect excellent energy and time resolutions at the same time. Made for the purpose of converting the solar energy to the electrical energy, the photovoltaic cells have the similar structure as silicon surface barrier detectors, except for their much thinner pn junctions and, as a result much larger junction capacities, which is a major disadvantage for photovoltaic cells as fission fragment detectors. In order to get an acceptable energy resolution and a time resolution as good as possible, it is necessary to design a preamplifier specially adapted to cells, which plays a very important role in the utilization of photovoltaic cells as detectors. In the present work we analyze the electrical signal from a cell when hit by a fission fragment, and propose a new type cell oriented preamplifier of voltage, with which we can use a cell up to 10 cm 2 , and obtain a time resolution better than 16 ns [fr

  14. Sex enhances adaptation by unlinking beneficial from detrimental mutations in experimental yeast populations

    Directory of Open Access Journals (Sweden)

    Gray Jeremy C

    2012-03-01

    Full Text Available Abstract Background The maintenance of sexuality is a classic problem in evolutionary biology because it is a less efficient mode of reproduction compared with asexuality; however, many organisms are sexual. Theoretical work suggests sex facilitates natural selection, and experimental data support this. However, there are fewer experimental studies that have attempted to determine the mechanisms underlying the advantage of sex. Two main classes of hypotheses have been proposed to explain its advantage: detrimental mutation clearance and beneficial mutation accumulation. Here we attempt to experimentally differentiate between these two classes by evolving Saccharomyces cerevisiae populations that differ only in their ability to undergo sex, and also manipulate mutation rate. We cannot manipulate the types of mutation that occur, but instead propagate populations in both stressful and permissive environments and assume that the extent of detrimental mutation clearance and beneficial mutation incorporation differs between them. Results After 300 mitotic generations interspersed with 11 rounds of sex we found there was no change or difference in fitness between sexuals and asexuals propagated in the permissive environment, regardless of mutation rate. Sex conferred a greater extent of adaptation in the stressful environment, and wild-type and elevated mutation rate sexual populations adapted equivalently. However, the asexual populations with an elevated mutation rate appeared more retarded in their extent of adaptation compared to asexual wild-type populations. Conclusions Sex provided no advantage in the permissive environment where beneficial mutations were rare. We could not evaluate if sex functioned to clear detrimental mutations more effectively or not here as no additional fitness load was observed in the mutator populations. However, in the stressful environment, where detrimental mutations were likely of more consequence, and where

  15. Single-cell analyses identify bioengineered niches for enhanced maintenance of hematopoietic stem cells.

    Science.gov (United States)

    Roch, Aline; Giger, Sonja; Girotra, Mukul; Campos, Vasco; Vannini, Nicola; Naveiras, Olaia; Gobaa, Samy; Lutolf, Matthias P

    2017-08-09

    The in vitro expansion of long-term hematopoietic stem cells (HSCs) remains a substantial challenge, largely because of our limited understanding of the mechanisms that control HSC fate choices. Using single-cell multigene expression analysis and time-lapse microscopy, here we define gene expression signatures and cell cycle hallmarks of murine HSCs and the earliest multipotent progenitors (MPPs), and analyze systematically single HSC fate choices in culture. Our analysis revealed twelve differentially expressed genes marking the quiescent HSC state, including four genes encoding cell-cell interaction signals in the niche. Under basal culture conditions, most HSCs rapidly commit to become early MPPs. In contrast, when we present ligands of the identified niche components such as JamC or Esam within artificial niches, HSC cycling is reduced and long-term multipotency in vivo is maintained. Our approach to bioengineer artificial niches should be useful in other stem cell systems.Haematopoietic stem cell (HSC) self-renewal is not sufficiently understood to recapitulate in vitro. Here, the authors generate gene signature and cell cycle hallmarks of single murine HSCs, and use identified endothelial receptors Esam and JamC as substrates to enhance HSC growth in engineered niches.

  16. Late Development of FcεRγneg Adaptive Natural Killer Cells Upon Human Cytomegalovirus Reactivation in Umbilical Cord Blood Transplantation Recipients

    Directory of Open Access Journals (Sweden)

    Letizia Muccio

    2018-05-01

    Full Text Available In human natural killer (NK cells, human cytomegalovirus (HCMV has been shown to be a driving force capable of inducing the expansion of a highly differentiated NKG2C+CD57+ subset, persisting over time in both HCMV+ healthy subjects and umbilical cord blood transplantation (UCBT recipients experiencing HCMV viral reactivation. In HCMV+ healthy subjects, such expanded NK-cells are characterized by epigenetic modifications that modulate their phenotypic and functional characteristics. In particular, an enhanced ADCC activity is detectable in NK cells lacking the signaling protein FcεRγ. Timing and mechanisms involved in the acquisition of HCMV-induced, adaptive-like features by NK cells are currently unknown. In this study, we investigated the de novo acquisition of several adaptive features in NK cells developing after UCBT by monitoring NK-cell differentiation for at least 2 years after transplant. In UCBT recipients experiencing HCMV reactivation, a rapid phenotypic reconfiguration occurred resulting in the expected expansion of CD56dim NKG2C+CD57+ NK cells. However, while certain HCMV-driven adaptive hallmarks, including high KIR, LILRB1, CD2 and low/negative NKG2A, Siglec-7, and CD161 expression, were acquired early after UCBT (namely by month 6, downregulation of the signaling protein FcεRγ was detected at a later time interval (i.e., by month 12. This feature characterized only a minor fraction of the HCMV-imprinted NKG2C+CD57+ CD56dim NK cell subset, while it was detectable in higher proportions of CD57+ NK cells lacking NKG2C. Interestingly, in patients developing a hyporesponsive CD56−CD16bright NK-cell subset, FcεRγ downregulation occurred in these cells earlier than in CD56dim NK cells. Our data suggest that the acquisition of a fully “adaptive” profile requires signals that may lack in UCBT recipients and/or longer time is needed to obtain a stable epigenetic reprogramming. On the other hand, we found that both HCMV

  17. Metabolic adaptations of Azospirillum brasilense to oxygen stress by cell-to-cell clumping and flocculation.

    Science.gov (United States)

    Bible, Amber N; Khalsa-Moyers, Gurusahai K; Mukherjee, Tanmoy; Green, Calvin S; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B; Alexandre, Gladys

    2015-12-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilic A. brasilense cells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Pre-adaptation to noisy Galvanic vestibular stimulation is associated with enhanced sensorimotor performance in novel vestibular environments

    Directory of Open Access Journals (Sweden)

    Steven T Moore

    2015-06-01

    Full Text Available Performance on a visuomotor task in the presence of novel vestibular stimulation was assessed in nine healthy subjects. Four subjects had previously been adapted to 120 minutes exposure to noisy Galvanic vestibular stimulation (GVS over 12 weekly sessions of 10 minutes; the remaining five subjects had never experienced GVS. Subjects were seated in a flight simulator and asked to null the roll motion of a visual bar presented on a screen using a joystick. Both the visual bar and the simulator cabin were moving in roll with a pseudorandom (sum of sines waveform that were uncorrelated. The cross correlation coefficient, which ranges from 1 (identical waveforms to 0 (unrelated waveforms, was calculated for the ideal (perfect nulling of bar motion and actual joystick input waveform for each subject. The cross correlation coefficient for the GVS-adapted group (0.90 [SD 0.04] was significantly higher (t[8]=3.162; p=0.013 than the control group (0.82 [SD 0.04], suggesting that prior adaptation to GVS was associated with an enhanced ability to perform the visuomotor task in the presence of novel vestibular noise.

  19. Unequal Protection of Video Streaming through Adaptive Modulation with a Trizone Buffer over Bluetooth Enhanced Data Rate

    Directory of Open Access Journals (Sweden)

    Razavi Rouzbeh

    2008-01-01

    Full Text Available Abstract Bluetooth enhanced data rate wireless channel can support higher-quality video streams compared to previous versions of Bluetooth. Packet loss when transmitting compressed data has an effect on the delivered video quality that endures over multiple frames. To reduce the impact of radio frequency noise and interference, this paper proposes adaptive modulation based on content type at the video frame level and content importance at the macroblock level. Because the bit rate of protected data is reduced, the paper proposes buffer management to reduce the risk of buffer overflow. A trizone buffer is introduced, with a varying unequal protection policy in each zone. Application of this policy together with adaptive modulation results in up to 4 dB improvement in objective video quality compared to fixed rate scheme for an additive white Gaussian noise channel and around 10 dB for a Gilbert-Elliott channel. The paper also reports a consistent improvement in video quality over a scheme that adapts to channel conditions by varying the data rate without accounting for the video frame packet type or buffer congestion.

  20. Unequal Protection of Video Streaming through Adaptive Modulation with a Trizone Buffer over Bluetooth Enhanced Data Rate

    Directory of Open Access Journals (Sweden)

    Rouzbeh Razavi

    2007-12-01

    Full Text Available Bluetooth enhanced data rate wireless channel can support higher-quality video streams compared to previous versions of Bluetooth. Packet loss when transmitting compressed data has an effect on the delivered video quality that endures over multiple frames. To reduce the impact of radio frequency noise and interference, this paper proposes adaptive modulation based on content type at the video frame level and content importance at the macroblock level. Because the bit rate of protected data is reduced, the paper proposes buffer management to reduce the risk of buffer overflow. A trizone buffer is introduced, with a varying unequal protection policy in each zone. Application of this policy together with adaptive modulation results in up to 4 dB improvement in objective video quality compared to fixed rate scheme for an additive white Gaussian noise channel and around 10 dB for a Gilbert-Elliott channel. The paper also reports a consistent improvement in video quality over a scheme that adapts to channel conditions by varying the data rate without accounting for the video frame packet type or buffer congestion.

  1. Adaptive and Pathogenic Responses to Stress by Stem Cells during Development.

    Science.gov (United States)

    Mansouri, Ladan; Xie, Yufen; Rappolee, Daniel A

    2012-12-10

    Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induced differentiation which generates minimal necessary function by producing more differentiated product/cell. This compensatory differentiation is accompanied by a second strategy to insure organismal survival as multipotent and pluripotent stem cells differentiate into the lineages in their repertoire. During stressed differentiation, the first lineage in the repertoire is increased and later lineages are suppressed, thus prioritized differentiation occurs. Compensatory and prioritized differentiation is regulated by at least two types of stress enzymes. AMP-activated protein kinase (AMPK) which mediates loss of nuclear potency factors and stress-activated protein kinase (SAPK) that does not. SAPK mediates an increase in the first essential lineage and decreases in later lineages in placental stem cells. The clinical significance of compensatory and prioritized differentiation is that stem cell pools are depleted and imbalanced differentiation leads to gestational diseases and long term postnatal pathologies.

  2. Adaptive and Pathogenic Responses to Stress by Stem Cells during Development

    Directory of Open Access Journals (Sweden)

    Daniel A. Rappolee

    2012-12-01

    Full Text Available Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induced differentiation which generates minimal necessary function by producing more differentiated product/cell. This compensatory differentiation is accompanied by a second strategy to insure organismal survival as multipotent and pluripotent stem cells differentiate into the lineages in their repertoire. During stressed differentiation, the first lineage in the repertoire is increased and later lineages are suppressed, thus prioritized differentiation occurs. Compensatory and prioritized differentiation is regulated by at least two types of stress enzymes. AMP-activated protein kinase (AMPK which mediates loss of nuclear potency factors and stress-activated protein kinase (SAPK that does not. SAPK mediates an increase in the first essential lineage and decreases in later lineages in placental stem cells. The clinical significance of compensatory and prioritized differentiation is that stem cell pools are depleted and imbalanced differentiation leads to gestational diseases and long term postnatal pathologies.

  3. Taurine Biosynthesis in a Fish Liver Cell Line (ZFL) Adapted to a Serum-Free Medium.

    Science.gov (United States)

    Liu, Chieh-Lun; Watson, Aaron M; Place, Allen R; Jagus, Rosemary

    2017-05-25

    Although taurine has been shown to play multiple important physiological roles in teleosts, little is known about the molecular mechanisms underlying dietary requirements. Cell lines can provide useful tools for deciphering biosynthetic pathways and their regulation. However, culture media and sera contain variable taurine levels. To provide a useful cell line for the investigation of taurine homeostasis, an adult zebrafish liver cell line (ZFL) has been adapted to a taurine-free medium by gradual accommodation to a commercially available synthetic medium, UltraMEM™-ITES. Here we show that ZFL cells are able to synthesize taurine and be maintained in medium without taurine. This has allowed for the investigation of the effects of taurine supplementation on cell growth, cellular amino acid pools, as well as the expression of the taurine biosynthetic pathway and taurine transporter genes in a defined fish cell type. After taurine supplementation, cellular taurine levels increase but hypotaurine levels stay constant, suggesting little suppression of taurine biosynthesis. Cellular methionine levels do not change after taurine addition, consistent with maintenance of taurine biosynthesis. The addition of taurine to cells grown in taurine-free medium has little effect on transcript levels of the biosynthetic pathway genes for cysteine dioxygenase (CDO), cysteine sulfinate decarboxylase (CSAD), or cysteamine dioxygenase (ADO). In contrast, supplementation with taurine causes a 30% reduction in transcript levels of the taurine transporter, TauT. This experimental approach can be tailored for the development of cell lines from aquaculture species for the elucidation of their taurine biosynthetic capacity.

  4. Flexible adaptation of male germ cells from female iPSCs of endangered Tokudaia osimensis.

    Science.gov (United States)

    Honda, Arata; Choijookhuu, Narantsog; Izu, Haruna; Kawano, Yoshihiro; Inokuchi, Mizuho; Honsho, Kimiko; Lee, Ah-Reum; Nabekura, Hiroki; Ohta, Hiroshi; Tsukiyama, Tomoyuki; Ohinata, Yasuhide; Kuroiwa, Asato; Hishikawa, Yoshitaka; Saitou, Mitinori; Jogahara, Takamichi; Koshimoto, Chihiro

    2017-05-01

    In mammals, the Y chromosome strictly influences the maintenance of male germ cells. Almost all mammalian species require genetic contributors to generate testes. An endangered species, Tokudaia osimensis , has a unique sex chromosome composition XO/XO, and genetic differences between males and females have not been confirmed. Although a distinctive sex-determining mechanism may exist in T. osimensis , it has been difficult to examine thoroughly in this rare animal species. To elucidate the discriminative sex-determining mechanism in T. osimensis and to find a strategy to prevent its possible extinction, we have established induced pluripotent stem cells (iPSCs) and derived interspecific chimeras using mice as the hosts and recipients. Generated iPSCs are considered to be in the so-called "true naïve" state, and T. osimensis iPSCs may contribute as interspecific chimeras to several different tissues and cells in live animals. Surprisingly, female T. osimensis iPSCs not only contributed to the female germ line in the interspecific mouse ovary but also differentiated into spermatocytes and spermatids that survived in the adult interspecific mouse testes. Thus, T. osimensis cells have high sexual plasticity through which female somatic cells can be converted to male germline cells. These findings suggest flexibility in T. osimensis cells, which can adapt their germ cell sex to the gonadal niche. The probable reduction of the extinction risk of an endangered species through the use of iPSCs is indicated by this study.

  5. Arabinogalactan Proteins Are Involved in Salt-Adaptation and Vesicle Trafficking in Tobacco by-2 Cell Cultures.

    Science.gov (United States)

    Olmos, Enrique; García De La Garma, Jesús; Gomez-Jimenez, Maria C; Fernandez-Garcia, Nieves

    2017-01-01

    Arabinogalactan proteins (AGPs) are a highly diverse family of glycoproteins that are commonly found in most plant species. However, little is known about the physiological and molecular mechanisms of their function. AGPs are involved in different biological processes such as cell differentiation, cell expansion, tissue development and somatic embryogenesis. AGPs are also involved in abiotic stress response such as salinity modulating cell wall expansion. In this study, we describe how salt-adaptation in tobacco BY-2 cell cultures induces important changes in arabinogalactan proteins distribution and contents. Using the immuno-dot blot technique with different anti-AGP antibodies (JIM13, JIM15, and others), we observed that AGPs were highly accumulated in the culture medium of salt-adapted tobacco cells, probably due to the action of phospholipases. We located these AGP epitopes using immunogold labeling in the cytoplasm associated to the endoplasmic reticulum, the golgi apparatus, and vesicles, plasma membrane and tonoplast. Our results show that salt-adaptation induced a significant reduction of the cytoplasm, plasma membrane and tonoplast content of these epitopes. Yariv reagent was added to the control and salt-adapted tobacco cell cultures, leading to cell death induction in control cells but not in salt-adapted cells. Ultrastructural and immunogold labeling revealed that cell death induced by Yariv reagent in control cells was due to the interaction of Yariv reagent with the AGPs linked to the plasma membranes. Finally, we propose a new function of AGPs as a possible sodium carrier through the mechanism of vesicle trafficking from the apoplast to the vacuoles in salt-adapted tobacco BY-2 cells. This mechanism may contribute to sodium homeostasis during salt-adaptation to high saline concentrations.

  6. Campylobacter jejuni type VI secretion system: roles in adaptation to deoxycholic acid, host cell adherence, invasion, and in vivo colonization.

    Science.gov (United States)

    Lertpiriyapong, Kvin; Gamazon, Eric R; Feng, Yan; Park, Danny S; Pang, Jassia; Botka, Georgina; Graffam, Michelle E; Ge, Zhongming; Fox, James G

    2012-01-01

    The recently identified type VI secretion system (T6SS) of proteobacteria has been shown to promote pathogenicity, competitive advantage over competing microorganisms, and adaptation to environmental perturbation. By detailed phenotypic characterization of loss-of-function mutants, in silico, in vitro and in vivo analyses, we provide evidence that the enteric pathogen, Campylobacter jejuni, possesses a functional T6SS and that the secretion system exerts pleiotropic effects on two crucial processes--survival in a bile salt, deoxycholic acid (DCA), and host cell adherence and invasion. The expression of T6SS during initial exposure to the upper range of physiological levels of DCA (0.075%-0.2%) was detrimental to C. jejuni proliferation, whereas down-regulation or inactivation of T6SS enabled C. jejuni to resist this effect. The C. jejuni multidrug efflux transporter gene, cmeA, was significantly up-regulated during the initial exposure to DCA in the wild type C. jejuni relative to the T6SS-deficient strains, suggesting that inhibition of proliferation is the consequence of T6SS-mediated DCA influx. A sequential modulation of the efflux transporter activity and the T6SS represents, in part, an adaptive mechanism for C. jejuni to overcome this inhibitory effect, thereby ensuring its survival. C. jejuni T6SS plays important roles in host cell adhesion and invasion as T6SS inactivation resulted in a reduction of adherence to and invasion of in vitro cell lines, while over-expression of a hemolysin co-regulated protein, which encodes a secreted T6SS component, greatly enhanced these processes. When inoculated into B6.129P2-IL-10(tm1Cgn) mice, the T6SS-deficient C. jejuni strains did not effectively establish persistent colonization, indicating that T6SS contributes to colonization in vivo. Taken together, our data demonstrate the importance of bacterial T6SS in host cell adhesion, invasion, colonization and, for the first time to our knowledge, adaptation to DCA

  7. Campylobacter jejuni type VI secretion system: roles in adaptation to deoxycholic acid, host cell adherence, invasion, and in vivo colonization.

    Directory of Open Access Journals (Sweden)

    Kvin Lertpiriyapong

    Full Text Available The recently identified type VI secretion system (T6SS of proteobacteria has been shown to promote pathogenicity, competitive advantage over competing microorganisms, and adaptation to environmental perturbation. By detailed phenotypic characterization of loss-of-function mutants, in silico, in vitro and in vivo analyses, we provide evidence that the enteric pathogen, Campylobacter jejuni, possesses a functional T6SS and that the secretion system exerts pleiotropic effects on two crucial processes--survival in a bile salt, deoxycholic acid (DCA, and host cell adherence and invasion. The expression of T6SS during initial exposure to the upper range of physiological levels of DCA (0.075%-0.2% was detrimental to C. jejuni proliferation, whereas down-regulation or inactivation of T6SS enabled C. jejuni to resist this effect. The C. jejuni multidrug efflux transporter gene, cmeA, was significantly up-regulated during the initial exposure to DCA in the wild type C. jejuni relative to the T6SS-deficient strains, suggesting that inhibition of proliferation is the consequence of T6SS-mediated DCA influx. A sequential modulation of the efflux transporter activity and the T6SS represents, in part, an adaptive mechanism for C. jejuni to overcome this inhibitory effect, thereby ensuring its survival. C. jejuni T6SS plays important roles in host cell adhesion and invasion as T6SS inactivation resulted in a reduction of adherence to and invasion of in vitro cell lines, while over-expression of a hemolysin co-regulated protein, which encodes a secreted T6SS component, greatly enhanced these processes. When inoculated into B6.129P2-IL-10(tm1Cgn mice, the T6SS-deficient C. jejuni strains did not effectively establish persistent colonization, indicating that T6SS contributes to colonization in vivo. Taken together, our data demonstrate the importance of bacterial T6SS in host cell adhesion, invasion, colonization and, for the first time to our knowledge

  8. Effects of the differentiating agents sodium butyrate and N-methylformamide on the oxygen enhancement ratio of human colon tumor cells

    International Nuclear Information System (INIS)

    Hallows, K.R.; Bliven, S.F.; Leith, J.T.

    1988-01-01

    We have previously shown that chronic adaptation of human tumor cells to the differentiation-inducing agents N-methylformamide (NMF) and sodium butyrate (NAB) increases the sensitivity of oxic cells to graded single doses of X rays. These studies were carried out to define the sensitivity of hypoxic cells after adaptation. Clone A colon tumor cells were grown for three passages in medium containing 170 mM NMF or 2 mM NAB and irradiated in suspension culture, after gassing with either oxygen (60 min) or ultrapure nitrogen (90 min), and complete survival curves were generated. Using the linear-quadratic equation to describe the data, it was found that NMF and NAB produced increased X-ray killing of hypoxic cells. At the 10% level of survival, the dose-modifying factors were about 1.20 and 1.25 for NMF- and NAB-adapted hypoxic cells, respectively, as compared to hypoxic control cells. However, since both oxic and hypoxic cells exhibited increased sensitivity after NMF and NAB adaptation, there was no major change in the oxygen enhancement ratio

  9. Endogenous adaptation to low oxygen modulates T-cell regulatory pathways in EAE.

    Science.gov (United States)

    Esen, Nilufer; Katyshev, Vladimir; Serkin, Zakhar; Katysheva, Svetlana; Dore-Duffy, Paula

    2016-01-19

    In the brain, chronic inflammatory activity may lead to compromised delivery of oxygen and glucose suggesting that therapeutic approaches aimed at restoring metabolic balance may be useful. In vivo exposure to chronic mild normobaric hypoxia (10 % oxygen) leads to a number of endogenous adaptations that includes vascular remodeling (angioplasticity). Angioplasticity promotes tissue survival. We have previously shown that induction of adaptive angioplasticity modulates the disease pattern in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). In the present study, we define mechanisms by which adaptation to low oxygen functionally ameliorates the signs and symptoms of EAE and for the first time show that tissue hypoxia may fundamentally alter neurodegenerative disease. C57BL/6 mice were immunized with MOG, and some of them were kept in the hypoxia chambers (day 0) and exposed to 10 % oxygen for 3 weeks, while the others were kept at normoxic environment. Sham-immunized controls were included in both hypoxic and normoxic groups. Animals were sacrificed at pre-clinical and peak disease periods for tissue collection and analysis. Exposure to mild hypoxia decreased histological evidence of inflammation. Decreased numbers of cluster of differentiation (CD)4+ T cells were found in the hypoxic spinal cords associated with a delayed Th17-specific cytokine response. Hypoxia-induced changes did not alter the sensitization of peripheral T cells to the MOG peptide. Exposure to mild hypoxia induced significant increases in anti-inflammatory IL-10 levels and an increase in the number of spinal cord CD25+FoxP3+ T-regulatory cells. Acclimatization to mild hypoxia incites a number of endogenous adaptations that induces an anti-inflammatory milieu. Further understanding of these mechanisms system may pinpoint possible new therapeutic targets to treat neurodegenerative disease.

  10. Role of CD5-negative CD8 T Cells in Adaptation to Antigenic ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of 3-oxotirucalla-7, 24-dien-21-oic acid on CD8+ T cell recovery in human immunodeficiency ..... enhances the probability of immune system recovery. ... PE: Fine tuning of TCR signaling by CD5. J Immunol.

  11. Spaceflight enhances cell aggregation and random budding in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Aurélie Crabbé

    Full Text Available This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans-induced genes involved in cell aggregation (similar to flocculation, which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p. infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the

  12. Lovastatin enhances in vitro radiation-induced apoptosis of rat B-cell lymphoma cells

    International Nuclear Information System (INIS)

    Rozados, V.R.; Hinrichsen, L.I.; Scharovsky, O.G.; Rosario Univ., Rosario; McDonnel, J.

    2005-01-01

    Our previous demonstration of an antimetastatic effect of lovastatin, both in rat sarcoma and lymphoma tumor-models, as well as the fact that lovastatin and radiation are able to stop the cell cycle in different phases, suggested the feasibility of a combined treatment. We studied the effect of the in vitro combined treatment of a B-cell rat lymphoma (L-TACB) with lovastatin and irradiation. The results herein obtained provide new information about the role of statins as radiosensitizers. The antitumor effect of the combined treatment was higher than that elicited by either treatment alone. This effect could be a consequence, at least in part, of an enhanced apoptosis

  13. The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction

    Directory of Open Access Journals (Sweden)

    Giulia Cheloni

    2017-01-01

    Full Text Available Previous studies based on low oxygen concentrations in the incubation atmosphere revealed that metabolic factors govern the maintenance of normal hematopoietic or leukemic stem cells (HSC and LSC. The physiological oxygen concentration in tissues ranges between 0.1 and 5.0%. Stem cell niches (SCN are placed in tissue areas at the lower end of this range (“hypoxic” SCN, to which stem cells are metabolically adapted and where they are selectively hosted. The data reported here indicated that driver oncogenic proteins of several leukemias are suppressed following cell incubation at oxygen concentration compatible with SCN physiology. This suppression is likely to represent a key positive regulator of LSC survival and maintenance (self-renewal within the SCN. On the other hand, LSC committed to differentiation, unable to stand suppression because of addiction to oncogenic signalling, would be unfit to home in SCN. The loss of oncogene addiction in SCN-adapted LSC has a consequence of crucial practical relevance: the refractoriness to inhibitors of the biological activity of oncogenic protein due to the lack of their molecular target. Thus, LSC hosted in SCN are suited to sustain the long-term maintenance of therapy-resistant minimal residual disease.

  14. Robust adaptive control for a hybrid solid oxide fuel cell system

    Science.gov (United States)

    Snyder, Steven

    2011-12-01

    Solid oxide fuel cells (SOFCs) are electrochemical energy conversion devices. They offer a number of advantages beyond those of most other fuel cells due to their high operating temperature (800-1000°C), such as internal reforming, heat as a byproduct, and faster reaction kinetics without precious metal catalysts. Mitigating fuel starvation and improving load-following capabilities of SOFC systems are conflicting control objectives. However, this can be resolved by the hybridization of the system with an energy storage device, such as an ultra-capacitor. In this thesis, a steady-state property of the SOFC is combined with an input-shaping method in order to address the issue of fuel starvation. Simultaneously, an overall adaptive system control strategy is employed to manage the energy sharing between the elements as well as to maintain the state-of-charge of the energy storage device. The adaptive control method is robust to errors in the fuel cell's fuel supply system and guarantees that the fuel cell current and ultra-capacitor state-of-charge approach their target values and remain uniformly, ultimately bounded about these target values. Parameter saturation is employed to guarantee boundedness of the parameters. The controller is validated through hardware-in-the-loop experiments as well as computer simulations.

  15. Enhancing adaptive capacity for restoring fire-dependent ecosystems: the Fire Learning Network's Prescribed Fire Training Exchanges

    Directory of Open Access Journals (Sweden)

    Andrew G. Spencer

    2015-09-01

    Full Text Available Prescribed fire is a critical tool for promoting restoration and increasing resilience in fire-adapted ecosystems, but there are barriers to its use, including a shortage of personnel with adequate ecological knowledge and operational expertise to implement prescribed fire across multijurisdictional landscapes. In the United States, recognized needs for both professional development and increased use of fire are not being met, often because of institutional limitations. The Fire Learning Network has been characterized as a multiscalar, collaborative network that works to enhance the adaptive capacity of fire management institutions, and this network developed the Prescribed Fire Training Exchanges (TREXs to address persistent challenges in increasing the capacity for prescribed fire implementation. Our research was designed to investigate where fire professionals face professional barriers, how the TREX addresses these, and in what ways the TREX may be contributing to the adaptive capacity of fire management institutions. We evaluated the training model using surveys, interviews, focus groups, and participant observation. We found that, although the training events cannot overcome all institutional barriers, they incorporate the key components of professional development in fire; foster collaboration, learning, and network building; and provide flexible opportunities with an emphasis on local context to train a variety of professionals with disparate needs. The strategy also offers an avenue for overcoming barriers faced by contingent and nonfederal fire professionals in attaining training and operational experience, thereby increasing the variety of actors and resources involved in fire management. Although it is an incremental step, the TREX is contributing to the adaptive capacity of institutions in social-ecological systems in which fire is a critical ecological process.

  16. Signs of impaired immunoregulation and enhanced effector T-cell responses in the primary antiphospholipid syndrome.

    Science.gov (United States)

    Jakiela, B; Iwaniec, T; Plutecka, H; Celinska-Lowenhoff, M; Dziedzina, S; Musial, J

    2016-04-01

    We investigated whether primary antiphospholipid syndrome (PAPS) is characterized by a deficiency in immunoregulatory pathways, a phenomenon recently implicated in the pathogenesis of autoimmune diseases. Serum levels of immunoregulatory (e.g., IL-10 and TGF-β1) and proinflammatory (e.g., IL-17A) cytokines were measured in PAPS, systemic lupus erythematosus (SLE) with secondary APS (SAPS), or without APS, and in healthy controls (n = 40 in each group). In a subgroup of PAPS patients we also compared phenotype and function (flow cytometry) of regulatory T-cells (Treg) and cytokine production by effector T-cells. Our major finding was decreased levels of TGF-β1 in PAPS and SAPS as compared to SLE without APS and controls. TGF-β1 was the lowest in PAPS patients showing high levels of aPL IgG with significant negative correlation with the titer. SLE patients were characterized by lower serum levels of IL-2 and increased IL-17A, as compared to the other groups. The numbers of circulating Treg cells and their phenotype (e.g., FoxP3 isoforms) were not disturbed in PAPS. However, surface expression of latency associated peptide (binds TGF-β) in activated FoxP3 + cells and in vitro production of TGF-β1 were decreased in PAPS patients with high titers of aPL IgG. Moreover, frequencies of cytokine producing effector T-helper cells (including Th17) were significantly elevated in this group. PAPS patients with high titers of aPL IgG antibodies were characterized by decreased systemic levels of TGF-β1 and its impaired production in vitro, suggesting impaired immunoregulation and enhanced adaptive autoimmune responses leading to the production of aPL antibodies. © The Author(s) 2015.

  17. Enhancement of combined heat and power economic dispatch using self adaptive real-coded genetic algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Subbaraj, P. [Kalasalingam University, Srivilliputhur, Tamilnadu 626 190 (India); Rengaraj, R. [Electrical and Electronics Engineering, S.S.N. College of Engineering, Old Mahabalipuram Road, Thirupporur (T.K), Kalavakkam, Kancheepuram (Dist.) 603 110, Tamilnadu (India); Salivahanan, S. [S.S.N. College of Engineering, Old Mahabalipuram Road, Thirupporur (T.K), Kalavakkam, Kancheepuram (Dist.) 603 110, Tamilnadu (India)

    2009-06-15

    In this paper, a self adaptive real-coded genetic algorithm (SARGA) is implemented to solve the combined heat and power economic dispatch (CHPED) problem. The self adaptation is achieved by means of tournament selection along with simulated binary crossover (SBX). The selection process has a powerful exploration capability by creating tournaments between two solutions. The better solution is chosen and placed in the mating pool leading to better convergence and reduced computational burden. The SARGA integrates penalty parameterless constraint handling strategy and simultaneously handles equality and inequality constraints. The population diversity is introduced by making use of distribution index in SBX operator to create a better offspring. This leads to a high diversity in population which can increase the probability towards the global optimum and prevent premature convergence. The SARGA is applied to solve CHPED problem with bounded feasible operating region which has large number of local minima. The numerical results demonstrate that the proposed method can find a solution towards the global optimum and compares favourably with other recent methods in terms of solution quality, handling constraints and computation time. (author)

  18. SIRT1 Gain of Function Does Not Mimic or Enhance the Adaptations to Intermittent Fasting

    Directory of Open Access Journals (Sweden)

    Marie Boutant

    2016-03-01

    Full Text Available Caloric restriction (CR has been shown to prevent the onset of insulin resistance and to delay age-related physiological decline in mammalian organisms. SIRT1, a NAD+-dependent deacetylase enzyme, has been suggested to mediate the adaptive responses to CR, leading to the speculation that SIRT1 activation could be therapeutically used as a CR-mimetic strategy. Here, we used a mouse model of moderate SIRT1 overexpression to test whether SIRT1 gain of function could mimic or boost the metabolic benefits induced by every-other-day feeding (EODF. Our results indicate that SIRT1 transgenesis does not affect the ability of EODF to decrease adiposity and improve insulin sensitivity. Transcriptomic analyses revealed that SIRT1 transgenesis and EODF promote very distinct adaptations in individual tissues, some of which can be even be metabolically opposite, as in brown adipose tissue. Therefore, whereas SIRT1 overexpression and CR both improve glucose metabolism and insulin sensitivity, the etiologies of these benefits are largely different.

  19. SIRT1 Gain of Function Does Not Mimic or Enhance the Adaptations to Intermittent Fasting.

    Science.gov (United States)

    Boutant, Marie; Kulkarni, Sameer S; Joffraud, Magali; Raymond, Frédéric; Métairon, Sylviane; Descombes, Patrick; Cantó, Carles

    2016-03-08

    Caloric restriction (CR) has been shown to prevent the onset of insulin resistance and to delay age-related physiological decline in mammalian organisms. SIRT1, a NAD(+)-dependent deacetylase enzyme, has been suggested to mediate the adaptive responses to CR, leading to the speculation that SIRT1 activation could be therapeutically used as a CR-mimetic strategy. Here, we used a mouse model of moderate SIRT1 overexpression to test whether SIRT1 gain of function could mimic or boost the metabolic benefits induced by every-other-day feeding (EODF). Our results indicate that SIRT1 transgenesis does not affect the ability of EODF to decrease adiposity and improve insulin sensitivity. Transcriptomic analyses revealed that SIRT1 transgenesis and EODF promote very distinct adaptations in individual tissues, some of which can be even be metabolically opposite, as in brown adipose tissue. Therefore, whereas SIRT1 overexpression and CR both improve glucose metabolism and insulin sensitivity, the etiologies of these benefits are largely different. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Performance enhancement for a GPS vector-tracking loop utilizing an adaptive iterated extended Kalman filter.

    Science.gov (United States)

    Chen, Xiyuan; Wang, Xiying; Xu, Yuan

    2014-12-09

    This paper deals with the problem of state estimation for the vector-tracking loop of a software-defined Global Positioning System (GPS) receiver. For a nonlinear system that has the model error and white Gaussian noise, a noise statistics estimator is used to estimate the model error, and based on this, a modified iterated extended Kalman filter (IEKF) named adaptive iterated Kalman filter (AIEKF) is proposed. A vector-tracking GPS receiver utilizing AIEKF is implemented to evaluate the performance of the proposed method. Through road tests, it is shown that the proposed method has an obvious accuracy advantage over the IEKF and Adaptive Extended Kalman filter (AEKF) in position determination. The results show that the proposed method is effective to reduce the root-mean-square error (RMSE) of position (including longitude, latitude and altitude). Comparing with EKF, the position RMSE values of AIEKF are reduced by about 45.1%, 40.9% and 54.6% in the east, north and up directions, respectively. Comparing with IEKF, the position RMSE values of AIEKF are reduced by about 25.7%, 19.3% and 35.7% in the east, north and up directions, respectively. Compared with AEKF, the position RMSE values of AIEKF are reduced by about 21.6%, 15.5% and 30.7% in the east, north and up directions, respectively.

  1. Adaptive regulation of taurine and beta-alanine uptake in a human kidney cell line from the proximal tubule

    DEFF Research Database (Denmark)

    Jessen, H; Jacobsen, Christian

    1997-01-01

    1. The underlying mechanisms involved in the adaptive regulation of beta-amino acid uptake in the human proximal tubule were examined by use of an immortalized human embryonic kidney epithelial cell line (IHKE). 2. The results indicated that the adaptive response to maintain whole-body taurine...

  2. Natural history of β-cell adaptation and failure in type 2 diabetes

    Science.gov (United States)

    Alejandro, Emilyn U.; Gregg, Brigid; Blandino-Rosano, Manuel; Cras-Méneur, Corentin; Bernal-Mizrachi, Ernesto

    2014-01-01

    Type 2 diabetes mellitus (T2D) is a complex disease characterized by β-cell failure in the setting of insulin resistance. The current evidence suggests that genetic predisposition, and environmental factors can impair the capacity of the β-cells to respond to insulin resistance and ultimately lead to their failure. However, genetic studies have demonstrated that known variants account for less than 10% of the overall estimated T2D risk, suggesting that additional unidentified factors contribute to susceptibility of this disease. In this review, we will discuss the different stages that contribute to the development of β-cell failure in T2D. We divide the natural history of this process in three major stages: susceptibility, β-cell adaptation and β-cell failure and provide an overview of the molecular mechanisms involved. Further research into mechanisms will reveal key modulators of β-cell failure and thus identify possible novel therapeutic targets and potential interventions to protect against β-cell failure. PMID:25542976

  3. Microenvironmental cues enhance mesenchymal stem cell-mediated immunomodulation and regulatory T-cell expansion.

    Science.gov (United States)

    Kadle, Rohini L; Abdou, Salma A; Villarreal-Ponce, Alvaro P; Soares, Marc A; Sultan, Darren L; David, Joshua A; Massie, Jonathan; Rifkin, William J; Rabbani, Piul; Ceradini, Daniel J

    2018-01-01

    Mesenchymal stem cells (MSCs) are known to both have powerful immunosuppressive properties and promote allograft tolerance. Determining the environmental oxygen tension and inflammatory conditions under which MSCs are optimally primed for this immunosuppressive function is essential to their utilization in promoting graft tolerance. Of particular interest is the mechanisms governing the interaction between MSCs and regulatory T cells (Tregs), which is relatively unknown. We performed our experiments utilizing rat bone marrow derived MSCs. We observed that priming MSCs in hypoxia promotes maintenance of stem-like characteristics, with greater expression of typical MSC cell-surface markers, increased proliferation, and maintenance of differentiation potential. Addition of autologous MSCs to CD4+/allogeneic endothelial cell (EC) co-culture increases regulatory T cell (Treg) proliferation, which is further enhanced when MSCs are primed in hypoxia. Furthermore, MSC-mediated Treg expansion does not require direct cell-cell contact. The expression of indolamine 2,3-dioxygenase, a mediator of MSC immunomodulation, increases when MSCs are primed in hypoxia, and inhibition of IDO significantly decreases the expansion of Tregs. Priming with inflammatory cytokines IFNγ and TNFα increases also expression of markers associated with MSC immunomodulatory function, but decreases MSC proliferation. The expression of IDO also increases when MSCs are primed with inflammatory cytokines. However, there is no increase in Treg expansion when MSCs are primed with IFNγ, suggesting an alternate mechanism for inflammatory-stimulated MSC immunomodulation. Overall, these results suggest that MSCs primed in hypoxia or inflammatory conditions are optimally primed for immunosuppressive function. These results provide a clearer picture of how to enhance MSC immunomodulation for clinical use.

  4. Stem cell factor enhances the survival of murine intestinal stem cells after photon irradiation

    International Nuclear Information System (INIS)

    Leigh, B.R.; Khan, W.; Hancock, S.L.

    1995-01-01

    Recombinant rat stem cell factor (SCF) has been shown to decrease lethality in mice exposed to total-body irradiation (TBI) in the lower range of lethality through radioprotection of hematopoietic stem cells and acceleration of bone marrow repopulation. This study evaluates the effect of SCF on the survival of the intestinal mucosal stem cell after TBI. This non-hematopoietic cell is clinically relevant. Gastrointestinal toxicity is common during and after abdominal and pelvic radiation therapy and limits the radiation dose in these regions. As observed with bone marrow, the administration of SCF to mice prior to TBI enhanced the survival of mouse duodenal crypt stem cells. The maximum enhancement of survival was seen when 100 μ/kg of SCF was given intraperitoneally 8 h before irradiation. This regimen increased the survival of duodenal crypt stem cells after 12.0 Gy TBI from 22.5 ± 0.7 per duodenal cross section for controls to 30.0 ± 1.7 after treatment with SCF (P=0.03). The TBI dose producing 50% mortality of 6 days (LD 50/6 ) was increased from 14.9 Gy for control mice to 19.0 Gy for mice treated with SCF (dose modification factor = 1.28). These findings demonstrate that SCF (dose modification factor = 1.28). These findings demonstrate that SCF has radioprotective effects on a non-hematopoietic stem cell population and suggest that SCF may be of clinical value in preventing radiation injury to the intestine. 29 refs., 4 figs

  5. A Simplified Method to Measure Choroidal Thickness Using Adaptive Compensation in Enhanced Depth Imaging Optical Coherence Tomography

    Science.gov (United States)

    Gupta, Preeti; Sidhartha, Elizabeth; Girard, Michael J. A.; Mari, Jean Martial; Wong, Tien-Yin; Cheng, Ching-Yu

    2014-01-01

    Purpose To evaluate a simplified method to measure choroidal thickness (CT) using commercially available enhanced depth imaging (EDI) spectral domain optical coherence tomography (SD-OCT). Methods We measured CT in 31 subjects without ocular diseases using Spectralis EDI SD-OCT. The choroid-scleral interface of the acquired images was first enhanced using a post-processing compensation algorithm. The enhanced images were then analysed using Photoshop. Two graders independently graded the images to assess inter-grader reliability. One grader re-graded the images after 2 weeks to determine intra-grader reliability. Statistical analysis was performed using intra-class correlation coefficient (ICC) and Bland-Altman plot analyses. Results Using adaptive compensation both the intra-grader reliability (ICC: 0.95 to 0.97) and inter-grader reliability (ICC: 0.93 to 0.97) were perfect for all five locations of CT. However, with the conventional technique of manual CT measurements using built-in callipers provided with the Heidelberg explorer software, the intra- (ICC: 0.87 to 0.94) and inter-grader reliability (ICC: 0.90 to 0.93) for all the measured locations is lower. Using adaptive compensation, the mean differences (95% limits of agreement) for intra- and inter-grader sub-foveal CT measurements were −1.3 (−3.33 to 30.8) µm and −1.2 (−36.6 to 34.2) µm, respectively. Conclusions The measurement of CT obtained from EDI SD-OCT using our simplified method was highly reliable and efficient. Our method is an easy and practical approach to improve the quality of choroidal images and the precision of CT measurement. PMID:24797674

  6. A simplified method to measure choroidal thickness using adaptive compensation in enhanced depth imaging optical coherence tomography.

    Directory of Open Access Journals (Sweden)

    Preeti Gupta

    Full Text Available PURPOSE: To evaluate a simplified method to measure choroidal thickness (CT using commercially available enhanced depth imaging (EDI spectral domain optical coherence tomography (SD-OCT. METHODS: We measured CT in 31 subjects without ocular diseases using Spectralis EDI SD-OCT. The choroid-scleral interface of the acquired images was first enhanced using a post-processing compensation algorithm. The enhanced images were then analysed using Photoshop. Two graders independently graded the images to assess inter-grader reliability. One grader re-graded the images after 2 weeks to determine intra-grader reliability. Statistical analysis was performed using intra-class correlation coefficient (ICC and Bland-Altman plot analyses. RESULTS: Using adaptive compensation both the intra-grader reliability (ICC: 0.95 to 0.97 and inter-grader reliability (ICC: 0.93 to 0.97 were perfect for all five locations of CT. However, with the conventional technique of manual CT measurements using built-in callipers provided with the Heidelberg explorer software, the intra- (ICC: 0.87 to 0.94 and inter-grader reliability (ICC: 0.90 to 0.93 for all the measured locations is lower. Using adaptive compensation, the mean differences (95% limits of agreement for intra- and inter-grader sub-foveal CT measurements were -1.3 (-3.33 to 30.8 µm and -1.2 (-36.6 to 34.2 µm, respectively. CONCLUSIONS: The measurement of CT obtained from EDI SD-OCT using our simplified method was highly reliable and efficient. Our method is an easy and practical approach to improve the quality of choroidal images and the precision of CT measurement.

  7. Assessment of fusion facility dose rate map using mesh adaptivity enhancements of hybrid Monte Carlo/deterministic techniques

    International Nuclear Information System (INIS)

    Ibrahim, Ahmad M.; Wilson, Paul P.; Sawan, Mohamed E.; Mosher, Scott W.; Peplow, Douglas E.; Grove, Robert E.

    2014-01-01

    Highlights: •Calculate the prompt dose rate everywhere throughout the entire fusion energy facility. •Utilize FW-CADIS to accurately perform difficult neutronics calculations for fusion energy systems. •Develop three mesh adaptivity algorithms to enhance FW-CADIS efficiency in fusion-neutronics calculations. -- Abstract: Three mesh adaptivity algorithms were developed to facilitate and expedite the use of the CADIS and FW-CADIS hybrid Monte Carlo/deterministic techniques in accurate full-scale neutronics simulations of fusion energy systems with immense sizes and complicated geometries. First, a macromaterial approach enhances the fidelity of the deterministic models without changing the mesh. Second, a deterministic mesh refinement algorithm generates meshes that capture as much geometric detail as possible without exceeding a specified maximum number of mesh elements. Finally, a weight window coarsening algorithm decouples the weight window mesh and energy bins from the mesh and energy group structure of the deterministic calculations in order to remove the memory constraint of the weight window map from the deterministic mesh resolution. The three algorithms were used to enhance an FW-CADIS calculation of the prompt dose rate throughout the ITER experimental facility and resulted in a 23.3% increase in the number of mesh tally elements in which the dose rates were calculated in a 10-day Monte Carlo calculation. Additionally, because of the significant increase in the efficiency of FW-CADIS simulations, the three algorithms enabled this difficult calculation to be accurately solved on a regular computer cluster, eliminating the need for a world-class super computer

  8. Adaptive cellular structures and devices with internal features for enhanced structural performance

    Science.gov (United States)

    Pontecorvo, Michael Eugene

    This dissertation aims to develop a family of cellular and repeatable devices that exhibit a variety of force-displacement behaviors. It is envisioned that these cellular structures might be used either as stand-alone elements, or combined and repeated to create multiple types of structures (i.e. buildings, ship hulls, vehicle subfloors, etc.) with the ability to passively or actively perform multiple functions (harmonic energy dissipation, impact mitigation, modulus change) over a range of loading types, amplitudes, and frequencies. To accomplish this goal, this work combines repeatable structural frameworks, such as that provided by a hexagonal cellular structure, with internal structural elements such as springs, viscous dampers, buckling plates, bi-stable von Mises trusses (VMTs), and pneumatic artificial muscles (PAMs). The repeatable framework serves to position damping and load carrying elements throughout the structure, and the configuration of the internal elements allow each cell to be tuned to exhibit a desired force-displacement response. Therefore, gradient structures or structures with variable load paths can be created for an optimal global response to a range of loads. This dissertation focuses on the development of cellular structures for three functions: combined load-carrying capability with harmonic energy dissipation, impact mitigation, and cell modulus variation. One or more conceptual designs are presented for devices that can perform each of these functions, and both experimental measurements and simulations are used to gain a fundamental understanding of each device. Chapter 2 begins with a presentation of a VMT model that is the basis for many of the elements. The equations of motion for the VMT are derived and the static and dynamic behavior of the VMT are discussed in detail. Next, two metrics for the energy dissipation of the VMT - hysteresis loop area and loss factor - are presented. The responses of the VMT to harmonic displacement

  9. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.

    Science.gov (United States)

    Flavahan, William A; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E; Weil, Robert J; Nakano, Ichiro; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Li, Meizhang; Lathia, Justin D; Rich, Jeremy N; Hjelmeland, Anita B

    2013-10-01

    Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

  10. Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses.

    Science.gov (United States)

    Mahanty, Siddhartha; Hutchinson, Karen; Agarwal, Sudhanshu; McRae, Michael; Rollin, Pierre E; Pulendran, Bali

    2003-03-15

    Acute infection of humans with Ebola and Lassa viruses, two principal etiologic agents of hemorrhagic fevers, often results in a paradoxical pattern of immune responses: early infection, characterized by an outpouring of inflammatory mediators such as TNF-alpha, IL-1 beta, and IL-6, vs late stage infections, which are associated with poor immune responses. The mechanisms underlying these diverse outcomes are poorly understood. In particular, the role played by cells of the innate immune system, such as dendritic cells (DC), is not known. In this study, we show that Ebola and Lassa viruses infect human monocyte-derived DC and impair their function. Monocyte-derived DC exposed to either virus fail to secrete proinflammatory cytokines, do not up-regulate costimulatory molecules, and are poor stimulators of T cells. These data represent the first evidence for a mechanism by which Ebola and Lassa viruses target DC to impair adaptive immunity.

  11. Super-resolution pupil filtering for visual performance enhancement using adaptive optics

    Science.gov (United States)

    Zhao, Lina; Dai, Yun; Zhao, Junlei; Zhou, Xiaojun

    2018-05-01

    Ocular aberration correction can significantly improve visual function of the human eye. However, even under ideal aberration correction conditions, pupil diffraction restricts the resolution of retinal images. Pupil filtering is a simple super-resolution (SR) method that can overcome this diffraction barrier. In this study, a 145-element piezoelectric deformable mirror was used as a pupil phase filter because of its programmability and high fitting accuracy. Continuous phase-only filters were designed based on Zernike polynomial series and fitted through closed-loop adaptive optics. SR results were validated using double-pass point spread function images. Contrast sensitivity was further assessed to verify the SR effect on visual function. An F-test was conducted for nested models to statistically compare different CSFs. These results indicated CSFs for the proposed SR filter were significantly higher than the diffraction correction (p vision optical correction of the human eye.

  12. Enhancing the Frequency Adaptability of Periodic Current Controllers for Grid-Connected Power Converters

    DEFF Research Database (Denmark)

    Yang, Yongheng; Zhou, Keliang; Blaabjerg, Frede

    2015-01-01

    It is mandatory for grid-connected power converters to synchronize the feed-in currents with the grid. Moreover, the power converters should produce feed-in currents with low total harmonic distortions according to the demands, by employing advanced current controllers, e.g., Proportional Resonant...... deviations. Experiments on a single-phase grid-connected inverter system are presented, which have verified the proposals and also the effectiveness of the frequency adaptive current controllers....... (PR) and Repetitive Controllers (RC). The synchronization is actually to detect the instantaneous grid information (e.g., frequency and phase of the grid voltage) for the current control, which is commonly performed by a Phase-Locked-Loop (PLL) system. As a consequence, harmonics and deviations...

  13. Crew resource management training adapted to nuclear power plant operators for enhancing safety attitude

    International Nuclear Information System (INIS)

    Ishibashi, Akira; Kitamura, Masaharu; Takahashi, Makoto

    2015-01-01

    A conventional training program for nuclear power plant operators mainly focuses on the improvement of knowledge and skills of individual operators. Although it has certainly contributed to safety operation of nuclear power plants, some recent incidents have indicated the necessity of an additional training program aiming at the improvement of team performance. In the aviation domain, crew resource management (CRM) training has demonstrated the effectiveness in resolving team management issues of flight crews, aircraft maintenance crews, and so on. In the present research, we attempt to introduce the CRM concept into operator training in nuclear power plant for the training of conceptual skill (that is, non-technical skill). In this paper an adapted CRM training for nuclear power plant operators is proposed. The proposed training method has been practically utilized in the training course of the managers of nuclear power plants. (author)

  14. An enhanced block matching algorithm for fast elastic registration in adaptive radiotherapy

    International Nuclear Information System (INIS)

    Malsch, U; Thieke, C; Huber, P E; Bendl, R

    2006-01-01

    Image registration has many medical applications in diagnosis, therapy planning and therapy. Especially for time-adaptive radiotherapy, an efficient and accurate elastic registration of images acquired for treatment planning, and at the time of the actual treatment, is highly desirable. Therefore, we developed a fully automatic and fast block matching algorithm which identifies a set of anatomical landmarks in a 3D CT dataset and relocates them in another CT dataset by maximization of local correlation coefficients in the frequency domain. To transform the complete dataset, a smooth interpolation between the landmarks is calculated by modified thin-plate splines with local impact. The concept of the algorithm allows separate processing of image discontinuities like temporally changing air cavities in the intestinal track or rectum. The result is a fully transformed 3D planning dataset (planning CT as well as delineations of tumour and organs at risk) to a verification CT, allowing evaluation and, if necessary, changes of the treatment plan based on the current patient anatomy without time-consuming manual re-contouring. Typically the total calculation time is less than 5 min, which allows the use of the registration tool between acquiring the verification images and delivering the dose fraction for online corrections. We present verifications of the algorithm for five different patient datasets with different tumour locations (prostate, paraspinal and head-and-neck) by comparing the results with manually selected landmarks, visual assessment and consistency testing. It turns out that the mean error of the registration is better than the voxel resolution (2 x 2 x 3 mm 3 ). In conclusion, we present an algorithm for fully automatic elastic image registration that is precise and fast enough for online corrections in an adaptive fractionated radiation treatment course

  15. Multimodal adaptive optics for depth-enhanced high-resolution ophthalmic imaging

    Science.gov (United States)

    Hammer, Daniel X.; Mujat, Mircea; Iftimia, Nicusor V.; Lue, Niyom; Ferguson, R. Daniel

    2010-02-01

    We developed a multimodal adaptive optics (AO) retinal imager for diagnosis of retinal diseases, including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinitis pigmentosa (RP). The development represents the first ever high performance AO system constructed that combines AO-corrected scanning laser ophthalmoscopy (SLO) and swept source Fourier domain optical coherence tomography (SSOCT) imaging modes in a single compact clinical prototype platform. The SSOCT channel operates at a wavelength of 1 μm for increased penetration and visualization of the choriocapillaris and choroid, sites of major disease activity for DR and wet AMD. The system is designed to operate on a broad clinical population with a dual deformable mirror (DM) configuration that allows simultaneous low- and high-order aberration correction. The system also includes a wide field line scanning ophthalmoscope (LSO) for initial screening, target identification, and global orientation; an integrated retinal tracker (RT) to stabilize the SLO, OCT, and LSO imaging fields in the presence of rotational eye motion; and a high-resolution LCD-based fixation target for presentation to the subject of stimuli and other visual cues. The system was tested in a limited number of human subjects without retinal disease for performance optimization and validation. The system was able to resolve and quantify cone photoreceptors across the macula to within ~0.5 deg (~100-150 μm) of the fovea, image and delineate ten retinal layers, and penetrate to resolve targets deep into the choroid. In addition to instrument hardware development, analysis algorithms were developed for efficient information extraction from clinical imaging sessions, with functionality including automated image registration, photoreceptor counting, strip and montage stitching, and segmentation. The system provides clinicians and researchers with high-resolution, high performance adaptive optics imaging to help

  16. The role of the adaptive immune system in burn-induced heterotopic ossification and mesenchymal cell osteogenic differentiation.

    Science.gov (United States)

    Ranganathan, Kavitha; Agarwal, Shailesh; Cholok, David; Loder, Shawn; Li, Jonathan; Sung Hsieh, Hsiao Hsin; Wang, Stewart C; Buchman, Steven R; Levi, Benjamin

    2016-11-01

    Heterotopic ossification (HO) is the pathologic process of extraskeletal bone formation. Although the exact etiology remains unknown, inflammation appears to catalyze disease progression. The goal of this study is to determine the impact of the adaptive immune system on HO. HO was induced in 8-wk-old control C57BL/6 and immunocompromised Rag1tm1Mom (Rag1 KO) male mice deficient in B- and T-lymphocytes via combined Achilles tenotomy and burn injury. Microcomputed tomography quantified the extent of HO formation at the tenotomy site. Adipose-derived mesenchymal stem cells were harvested to evaluate osteogenic differentiation potential. Areas of developing HO demonstrated substantial enrichment of CD45 + leukocytes at 3 wk after injury. HO from Rag1 KO mice was substantially less mature with foci of cartilage and disorganized trabecular bone present 12 wk after injury. Rag1 KO mice formed 60% less bone compared to immunocompetent controls (4.67 ± 1.5 mm versus 7.76 ± 0.65 mm; P = 0.001). Tartrate-resistant acid phosphatase staining and immunofluorescent analysis of osteoprotegerin and nuclear factor kappa-light-chain-enhancer of activated B cells demonstrated no appreciable difference in osteoclast number or activation. Alizarin red staining in vitro demonstrated a significant decrease in osteogenic potential in immunocompromised mice compared to controls (29.1 ± 0.54 mm versus 12.1 ± 0.14 mm; P role for the adaptive immune system in the development of HO. In the absence of mature B- and T-lymphocytes, HO growth and development are attenuated. Furthermore, we demonstrate that mesenchymal populations from B- and T-cell deficient mice are inherently less osteogenic. This study identifies a potential therapeutic role for modulation of the adaptive immune system in the treatment of HO. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair.

    Science.gov (United States)

    Shafiq, Muhammad; Jung, Youngmee; Kim, Soo Hyun

    2016-06-01

    Stem cells are a promising solution for the treatment of a variety of diseases. However, the limited survival and engraftment of transplanted cells due to a hostile ischemic environment is a bottleneck for effective utilization and commercialization. Within this environment, the majority of transplanted cells undergo apoptosis prior to participating in lineage differentiation and cellular integration. Therefore, in order to maximize the clinical utility of stem/progenitor cells, strategies must be employed to increase their adhesion, retention, and engraftment in vivo. Here, we reviewed key strategies that are being adopted to enhance the survival, retention, and engraftment of transplanted stem cells through the manipulation of both the stem cells and the surrounding environment. We describe how preconditioning of cells or cell manipulations strategies can enhance stem cell survival and engraftment after transplantation. We also discuss how biomaterials can enhance the function of stem cells for effective tissue regeneration. Biomaterials can incorporate or mimic extracellular function (ECM) function and enhance survival or differentiation of transplanted cells in vivo. Biomaterials can also promote angiogenesis, enhance engraftment and differentiation, and accelerate electromechanical integration of transplanted stem cells. Insight gained from this review may direct the development of future investigations and clinical trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Solid-State NMR on bacterial cells: selective cell wall signal enhancement and resolution improvement using dynamic nuclear polarization

    International Nuclear Information System (INIS)

    Takahashi, Hiroki; Bardet, Michel; De Paepe, Gael; Hediger, Sabine; Ayala, Isabel; Simorre, Jean-Pierre

    2013-01-01

    Dynamic nuclear polarization (DNP) enhanced solid-state nuclear magnetic resonance (NMR) has recently emerged as a powerful technique for the study of material surfaces. In this study, we demonstrate its potential to investigate cell surface in intact cells. Using Bacillus subtilis bacterial cells as an example, it is shown that the polarizing agent 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL) has a strong binding affinity to cell wall polymers (peptidoglycan). This particular interaction is thoroughly investigated with a systematic study on extracted cell wall materials, disrupted cells, and entire cells, which proved that TOTAPOL is mainly accumulating in the cell wall. This property is used on one hand to selectively enhance or suppress cell wall signals by controlling radical concentrations and on the other hand to improve spectral resolution by means of a difference spectrum. Comparing DNP-enhanced and conventional solid-state NMR, an absolute sensitivity ratio of 24 was obtained on the entire cell sample. This important increase in sensitivity together with the possibility of enhancing specifically cell wall signals and improving resolution really opens new avenues for the use of DNP-enhanced solid-state NMR as an on-cell investigation tool. (authors)

  19. Solid-state NMR on bacterial cells: selective cell wall signal enhancement and resolution improvement using dynamic nuclear polarization.

    Science.gov (United States)

    Takahashi, Hiroki; Ayala, Isabel; Bardet, Michel; De Paëpe, Gaël; Simorre, Jean-Pierre; Hediger, Sabine

    2013-04-03

    Dynamic nuclear polarization (DNP) enhanced solid-state nuclear magnetic resonance (NMR) has recently emerged as a powerful technique for the study of material surfaces. In this study, we demonstrate its potential to investigate cell surface in intact cells. Using Bacillus subtilis bacterial cells as an example, it is shown that the polarizing agent 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL) has a strong binding affinity to cell wall polymers (peptidoglycan). This particular interaction is thoroughly investigated with a systematic study on extracted cell wall materials, disrupted cells, and entire cells, which proved that TOTAPOL is mainly accumulating in the cell wall. This property is used on one hand to selectively enhance or suppress cell wall signals by controlling radical concentrations and on the other hand to improve spectral resolution by means of a difference spectrum. Comparing DNP-enhanced and conventional solid-state NMR, an absolute sensitivity ratio of 24 was obtained on the entire cell sample. This important increase in sensitivity together with the possibility of enhancing specifically cell wall signals and improving resolution really opens new avenues for the use of DNP-enhanced solid-state NMR as an on-cell investigation tool.

  20. Active screen plasma nitriding enhances cell attachment to polymer surfaces

    International Nuclear Information System (INIS)

    Kaklamani, Georgia; Bowen, James; Mehrban, Nazia; Dong, Hanshan; Grover, Liam M.; Stamboulis, Artemis

    2013-01-01

    Active screen plasma nitriding (ASPN) is a well-established technique used for the surface modification of materials, the result of which is often a product with enhanced functional performance. Here we report the modification of the chemical and mechanical properties of ultra-high molecular weight poly(ethylene) (UHMWPE) using 80:20 (v/v) N 2 /H 2 ASPN, followed by growth of 3T3 fibroblasts on the treated and untreated polymer surfaces. ASPN-treated UHMWPE showed extensive fibroblast attachment within 3 h of seeding, whereas fibroblasts did not successfully attach to untreated UHMWPE. Fibroblast-coated surfaces were maintained for up to 28 days, monitoring their metabolic activity and morphology throughout. The chemical properties of the ASPN-treated UHMWPE surface were studied using X-ray photoelectron spectroscopy, revealing the presence of C-N, C=N, and C≡N chemical bonds. The elastic modulus, surface topography, and adhesion properties of the ASPN-treated UHMWPE surface were studied over 28 days during sample storage under ambient conditions and during immersion in two commonly used cell culture media.

  1. Enhancement of Adaptive Cluster Hierarchical Routing Protocol using Distance and Energy for Wireless Sensor Networks

    International Nuclear Information System (INIS)

    Nawar, N.M.; Soliman, S.E.; Kelash, H.M.; Ayad, N.M.

    2014-01-01

    The application of wireless networking is widely used in nuclear applications. This includes reactor control and fire dedication system. This paper is devoted to the application of this concept in the intrusion system of the Radioisotope Production Facility (RPF) of the Egyptian Atomic Energy Authority. This includes the tracking, monitoring and control components of this system. The design and implementation of wireless sensor networks has become a hot area of research due to the extensive use of sensor networks to enable applications that connect the physical world to the virtual world [1-2]. The original LEACH is named a communication protocol (clustering-based); the extended LEACH’s stochastic cluster head selection algorithm by a deterministic component. Depending on the network configuration an increase of network lifetime can be accomplished [3]. The proposed routing mechanisms after enhancement divide the nodes into clusters. A cluster head performs its task which is considerably more energy-intensive than the rest of the nodes inside sensor network. So, nodes rotate tasks at different rounds between a cluster head and other sensors throughout the lifetime of the network to balance the energy dissipation [4-5].The performance improvement when using routing protocol after enhancement of the algorithm which takes into consideration the distance and the remaining energy for choosing the cluster head by obtains from the advertise message. Network Simulator (Ns2 simulator) is used to prove that LEACH after enhancement performs better than the original LEACH protocol in terms of Average Energy, Network Life Time, Delay, Throughput and Overhead.

  2. Connectivity-Enhanced Route Selection and Adaptive Control for the Chevrolet Volt: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Gonder, J.; Wood, E.; Rajagopalan, S.

    2014-09-01

    The National Renewable Energy Laboratory and General Motors evaluated connectivity-enabled efficiency enhancements for the Chevrolet Volt. A high-level model was developed to predict vehicle fuel and electricity consumption based on driving characteristics and vehicle state inputs. These techniques were leveraged to optimize energy efficiency via green routing and intelligent control mode scheduling, which were evaluated using prospective driving routes between tens of thousands of real-world origin/destination pairs. The overall energy savings potential of green routing and intelligent mode scheduling was estimated at 5% and 3% respectively. These represent substantial opportunities considering that they only require software adjustments to implement.

  3. Adaptive Response to ionizing Radiation Induced by Low Doses of Gamma Rays in Human Lymphoblastoid Cell Lines

    International Nuclear Information System (INIS)

    Seong, Jin Sil; Suh, Chang Ok; Kim, Gwi Eon

    1994-01-01

    When cells are exposed to low doses of a mutagenic or clastogenic agents, they often become less sensitive to the effects of a higher does administered subsequently. Such adaptive responses were first described in Escherichia coli and mammalian cells to low doses of an alkylating agent. Since most of the studies have been carried out with human lymphocytes, it is urgently necessary to study this effect in different cellular systems. Its relation with inherent cellular radiosensitivity and underlying mechanism also remain to be answered. In this study, adaptive response by 1 cGy of gamma rays was investigated in three human lymphoblastoid cell lines which were derived from ataxia telangiectasia homozygote, ataxia telangiectasia heterozygote, and normal individual. Experiments were carried out by delivering 1 cGy followed by 50 cGy of gamma radiation and chromatid breaks were scored as an endpoint. The results indicate that prior exposure to 1 cGy of gamma rays reduces the number of chromatid breaks induced by subsequent higher does (50 cGy). The expression of this adaptive response was similar among three cell lines despite of their different radiosensitivity. When 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, was added after 50 cGy, adaptive responses were abolished in all the tested cell lines. Therefore it is suggested that the adaptive response can be observed in human lymphoblastoid cell lines. Which was first documented through this study. The expression of adaptive response was similar among the cell lines regardless of their radiosensitivity. The elimination of the adaptive response by 3-aminobenzamide is consistent with the proposal that this adaptive response is the result of the induction of a certain chromosomal repair mechanism

  4. Plasmon enhanced power conversion efficiency in inverted bulk heterojunction organic solar cell

    Science.gov (United States)

    Mohan, Minu; Ramkumar, S.; Namboothiry, Manoj A. G.

    2017-08-01

    P3HT:PCBM is one of the most studied polymer-fullerene system. However the reported power conversion efficiency (PCE) values falls within the range of 4% to 5%. The thin film architecture in OPVs exhibits low PCE compared to inorganic photovoltaic cells. This is mainly due to the low exciton diffusion length that limits the active layer thickness which in turn reduces the absorption of incident light. Several strategies are adapted in order to increase the absorption in the active layer without increasing the film thickness. Inclusion of metal nanoparticles into the polymer layer of bulk heterojunction (BHJ) solar cells is one of the promising methods. Incorporation of metal nanostructures increases the absorption of organic materials due to the high electromagnetic field strength in the vicinity of the excited surface plasmons. In this work, we used 60 nm Au plasmonic structures to improve the efficiency of organic solar cell. The prepared metal nano structures were characterized through scanning electron microscopy (SEM), and UV-Visible spectroscopy techniques. These prepared metallic nanoparticles can be incorporated either into the electron transport layer (ETL) or into the active P3HT:PC71BM layer. The effect of incorporation of plasmonic gold (Au) nanoparticle in the inverted bulk heterojunction organic photovoltaic cells (OPVs) of P3HT:PC71BM fabricated in ambient air condition is in progress. Initial studies shows an 8.5% enhancement in the PCE with the incorporation of Au nanoparticles under AM1.5G light of intensity 1 Sun.

  5. Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility

    Science.gov (United States)

    Seumois, Grégory; Chavez, Lukas; Gerasimova, Anna; Lienhard, Matthias; Omran, Nada; Kalinke, Lukas; Vedanayagam, Maria; Ganesan, Asha Purnima V; Chawla, Ashu; Djukanović, Ratko; Ansel, K Mark; Peters, Bjoern; Rao, Anjana; Vijayanand, Pandurangan

    2014-01-01

    A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis. PMID:24997565

  6. The development of adaptive memory: Young children show enhanced retention of animacy-related information.

    Science.gov (United States)

    Aslan, Alp; John, Thomas

    2016-12-01

    Previous developmental work has indicated that animacy is a foundational ontogenetic category that is given priority already early in life. Here, we investigated whether such priority is also present in children's episodic memory, examining whether young children show enhanced retention of animacy-related information. Kindergartners and younger and older elementary school children were presented with fictitious (non)words (e.g., BULA, LAFE) paired with properties characteristic of humans (e.g., "likes music"), (nonhuman) animals (e.g., "builds nests"), and inanimate things (e.g., "has four edges") and were asked to rate the animacy status of each nonword. After a retention interval, a surprise recognition test for the nonwords was administered. We found enhanced recognition of nonwords paired with human and animal properties compared with (the same) nonwords paired with inanimate properties. The size of this animacy advantage was comparable across age groups, suggesting developmental invariance of the advantage over the age range examined (i.e., 4-11years). The results support a functional-evolutionary view on memory, suggesting that already young children's memory is "tuned" to process and retain animacy. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Naren Subbiah

    2017-01-01

    Full Text Available Phospholipid-based deformable nanovesicles (DNVs that have flexibility in shape offer an adaptable and facile method to encapsulate diverse classes of therapeutics and facilitate localized transdermal delivery while minimizing systemic exposure. Here we report the use of a microfluidic reactor for the synthesis of DNVs and show that alteration of input parameters such as flow speeds as well as molar and flow rate ratios increases entrapment efficiency of drugs and allows fine-tuning of DNV size, elasticity, and surface charge. To determine the ability of DNV-encapsulated drug to be delivered transdermally to a local site, we synthesized, characterized, and tested DNVs carrying the fluorescently labeled hydrophilic bisphosphonate drug AF-647 zoledronate (AF647-Zol. AF647-Zol DNVs were lyophilized, resuspended, and applied topically as a paste to the calvarial skin of mice. High-resolution fluorescent imaging and confocal microscopy revealed significant increase of encapsulated payload delivery to the target tissue—cranial bone—by DNVs as compared to nondeformable nanovesicles (NVs or aqueous drug solutions. Interestingly, NV delivery was not superior to aqueous drug solution. Our studies show that microfluidic reactor-synthesized DNVs can be produced in good yield, with high encapsulation efficiency, reproducibility, and stability after storage, and represent a useful vehicle for localized transdermal drug delivery.

  8. Enhanced optical alignment of a digital micro mirror device through Bayesian adaptive exploration

    Directory of Open Access Journals (Sweden)

    Kevin B. Wynne

    2017-12-01

    Full Text Available As the use of Digital Micro Mirror Devices (DMDs becomes more prevalent in optics research, the ability to precisely locate the Fourier “footprint” of an image beam at the Fourier plane becomes a pressing need. In this approach, Bayesian adaptive exploration techniques were employed to characterize the size and position of the beam on a DMD located at the Fourier plane. It couples a Bayesian inference engine with an inquiry engine to implement the search. The inquiry engine explores the DMD by engaging mirrors and recording light intensity values based on the maximization of the expected information gain. Using the data collected from this exploration, the Bayesian inference engine updates the posterior probability describing the beam’s characteristics. The process is iterated until the beam is located to within the desired precision. This methodology not only locates the center and radius of the beam with remarkable precision but accomplishes the task in far less time than a brute force search. The employed approach has applications to system alignment for both Fourier processing and coded aperture design.

  9. Enhanced optical alignment of a digital micro mirror device through Bayesian adaptive exploration

    Science.gov (United States)

    Wynne, Kevin B.; Knuth, Kevin H.; Petruccelli, Jonathan

    2017-12-01

    As the use of Digital Micro Mirror Devices (DMDs) becomes more prevalent in optics research, the ability to precisely locate the Fourier "footprint" of an image beam at the Fourier plane becomes a pressing need. In this approach, Bayesian adaptive exploration techniques were employed to characterize the size and position of the beam on a DMD located at the Fourier plane. It couples a Bayesian inference engine with an inquiry engine to implement the search. The inquiry engine explores the DMD by engaging mirrors and recording light intensity values based on the maximization of the expected information gain. Using the data collected from this exploration, the Bayesian inference engine updates the posterior probability describing the beam's characteristics. The process is iterated until the beam is located to within the desired precision. This methodology not only locates the center and radius of the beam with remarkable precision but accomplishes the task in far less time than a brute force search. The employed approach has applications to system alignment for both Fourier processing and coded aperture design.

  10. Adaptive Regulation of Osteopontin Production by Dendritic Cells Through the Bidirectional Interaction With Mesenchymal Stromal Cells

    Directory of Open Access Journals (Sweden)

    Sara Scutera

    2018-06-01

    Full Text Available Mesenchymal stromal cells (MSCs exert immunosuppressive effects on immune cells including dendritic cells (DCs. However, many details of the bidirectional interaction of MSCs with DCs are still unsolved and information on key molecules by which DCs can modulate MSC functions is limited. Here, we report that osteopontin (OPN, a cytokine involved in homeostatic and pathophysiologic responses, is constitutively expressed by DCs and regulated in the DC/MSC cocultures depending on the activation state of MSCs. Resting MSCs promoted OPN production, whereas the production of OPN was suppressed when MSCs were activated by proinflammatory cytokines (i.e., TNF-α, IL-6, and IL-1β. OPN induction required cell-to-cell contact, mediated at least in part, by β1 integrin (CD29. Conversely, activated MSCs inhibited the release of OPN via the production of soluble factors with a major role played by Prostaglandin E2 (PGE2. Accordingly, pretreatment with indomethacin significantly abrogated the MSC-mediated suppression of OPN while the direct addition of exogenous PGE2 inhibited OPN production by DCs. Furthermore, DC-conditioned medium promoted osteogenic differentiation of MSCs with a concomitant inhibition of adipogenesis. These effects were paralleled by the repression of the adipogenic markers PPARγ, adiponectin, and FABP4, and induction of the osteogenic markers alkaline phosphatase, RUNX2, and of the bone-anabolic chemokine CCL5. Notably, blocking OPN activity with RGD peptides or with an antibody against CD29, one of the OPN receptors, prevented the effects of DC-conditioned medium on MSC differentiation and CCL5 induction. Because MSCs have a key role in maintenance of bone marrow (BM hematopoietic stem cell niche through reciprocal regulation with immune cells, we investigated the possible MSC/DC interaction in human BM by immunohistochemistry. Although DCs (CD1c+ are a small percentage of BM cells, we demonstrated colocalization of CD271+ MSCs with

  11. Enhancing Artificial Bee Colony Algorithm with Self-Adaptive Searching Strategy and Artificial Immune Network Operators for Global Optimization

    Directory of Open Access Journals (Sweden)

    Tinggui Chen

    2014-01-01

    Full Text Available Artificial bee colony (ABC algorithm, inspired by the intelligent foraging behavior of honey bees, was proposed by Karaboga. It has been shown to be superior to some conventional intelligent algorithms such as genetic algorithm (GA, artificial colony optimization (ACO, and particle swarm optimization (PSO. However, the ABC still has some limitations. For example, ABC can easily get trapped in the local optimum when handing in functions that have a narrow curving valley, a high eccentric ellipse, or complex multimodal functions. As a result, we proposed an enhanced ABC algorithm called EABC by introducing self-adaptive searching strategy and artificial immune network operators to improve the exploitation and exploration. The simulation results tested on a suite of unimodal or multimodal benchmark functions illustrate that the EABC algorithm outperforms ACO, PSO, and the basic ABC in most of the experiments.

  12. Cell invasion in the spheroid sprouting assay: a spatial organisation analysis adaptable to cell behaviour.

    Directory of Open Access Journals (Sweden)

    Silvia Blacher

    Full Text Available The endothelial cell spheroid assay provides a suitable in vitro model to study (lymph angiogenesis and test pro- and anti-(lymph angiogenic factors or drugs. Usually, the extent of cell invasion, observed through optical microscopy, is measured. The present study proposes the spatial distribution of migrated cells as a new descriptor of the (lymph angiogenic response. The utility of this novel method rests with its capacity to locally characterise spheroid structure, allowing not only the investigation of single and collective cell invasion but also the evolution of the spheroid core itself. Moreover, the proposed method can be applied to 2D-projected spheroid images obtained by optical microscopy, as well as to 3D images acquired by confocal microscopy. To validate the proposed methodology, endothelial cell invasion was evaluated under different experimental conditions. The results were compared with widely used global parameters. The comparison shows that our method prevents local spheroid modifications from being overlooked and leading to the possible misinterpretation of results.

  13. Depletion of dendritic cells enhances innate anti-bacterial host defense through modulation of phagocyte homeostasis.

    Directory of Open Access Journals (Sweden)

    Stella E Autenrieth

    2012-02-01

    Full Text Available Dendritic cells (DCs as professional antigen-presenting cells play an important role in the initiation and modulation of the adaptive immune response. However, their role in the innate immune response against bacterial infections is not completely defined. Here we have analyzed the role of DCs and their impact on the innate anti-bacterial host defense in an experimental infection model of Yersinia enterocolitica (Ye. We used CD11c-diphtheria toxin (DT mice to deplete DCs prior to severe infection with Ye. DC depletion significantly increased animal survival after Ye infection. The bacterial load in the spleen of DC-depleted mice was significantly lower than that of control mice throughout the infection. DC depletion was accompanied by an increase in the serum levels of CXCL1, G-CSF, IL-1α, and CCL2 and an increase in the numbers of splenic phagocytes. Functionally, splenocytes from DC-depleted mice exhibited an increased bacterial killing capacity compared to splenocytes from control mice. Cellular studies further showed that this was due to an increased production of reactive oxygen species (ROS by neutrophils. Adoptive transfer of neutrophils from DC-depleted mice into control mice prior to Ye infection reduced the bacterial load to the level of Ye-infected DC-depleted mice, suggesting that the increased number of phagocytes with additional ROS production account for the decreased bacterial load. Furthermore, after incubation with serum from DC-depleted mice splenocytes from control mice increased their bacterial killing capacity, most likely due to enhanced ROS production by neutrophils, indicating that serum factors from DC-depleted mice account for this effect. In summary, we could show that DC depletion triggers phagocyte accumulation in the spleen and enhances their anti-bacterial killing capacity upon bacterial infection.

  14. Modeling of a 5-cell direct methanol fuel cell using adaptive-network-based fuzzy inference systems

    Science.gov (United States)

    Wang, Rongrong; Qi, Liang; Xie, Xiaofeng; Ding, Qingqing; Li, Chunwen; Ma, ChenChi M.

    The methanol concentrations, temperature and current were considered as inputs, the cell voltage was taken as output, and the performance of a direct methanol fuel cell (DMFC) was modeled by adaptive-network-based fuzzy inference systems (ANFIS). The artificial neural network (ANN) and polynomial-based models were selected to be compared with the ANFIS in respect of quality and accuracy. Based on the ANFIS model obtained, the characteristics of the DMFC were studied. The results show that temperature and methanol concentration greatly affect the performance of the DMFC. Within a restricted current range, the methanol concentration does not greatly affect the stack voltage. In order to obtain higher fuel utilization efficiency, the methanol concentrations and temperatures should be adjusted according to the load on the system.

  15. Modeling of a 5-cell direct methanol fuel cell using adaptive-network-based fuzzy inference systems

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Rongrong; Li, Chunwen [Department of Automation, Tsinghua University, Beijing 100084 (China); Qi, Liang; Xie, Xiaofeng [Institute of Nuclear and New Energy Technology, Tsinghua University, Beijing 100084 (China); Ding, Qingqing [Department of Electrical Engineering, Tsinghua University, Beijing 100084 (China); Ma, ChenChi M. [National Tsing Hua University, Hsinchu 300 (China)

    2008-12-01

    The methanol concentrations, temperature and current were considered as inputs, the cell voltage was taken as output, and the performance of a direct methanol fuel cell (DMFC) was modeled by adaptive-network-based fuzzy inference systems (ANFIS). The artificial neural network (ANN) and polynomial-based models were selected to be compared with the ANFIS in respect of quality and accuracy. Based on the ANFIS model obtained, the characteristics of the DMFC were studied. The results show that temperature and methanol concentration greatly affect the performance of the DMFC. Within a restricted current range, the methanol concentration does not greatly affect the stack voltage. In order to obtain higher fuel utilization efficiency, the methanol concentrations and temperatures should be adjusted according to the load on the system. (author)

  16. Resveratrol imparts photoprotection of normal cells and enhances the efficacy of radiation therapy in cancer cells.

    Science.gov (United States)

    Reagan-Shaw, Shannon; Mukhtar, Hasan; Ahmad, Nihal

    2008-01-01

    Solar radiation spans a whole range of electromagnetic spectrum including UV radiation, which are potentially harmful to normal cells as well as ionizing radiations which are therapeutically beneficial towards the killing of cancer cells. UV radiation is an established cause of a majority of skin cancers as well as precancerous conditions such as actinic keratosis. However, despite efforts to educate people about the use of sunscreens and protective clothing as preventive strategies, the incidence of skin cancer and other skin-related disorders are on the rise. This has generated an enormous interest towards finding alternative approaches for management of UV-mediated damages. Chemoprevention via nontoxic agents, especially botanical antioxidants, is one such approach that is being considered as a plausible strategy for prevention of photodamages including photocarcinogenesis. In this review, we have discussed the photoprotective effects of resveratrol, an antioxidant found in grapes and red wine, against UVB exposure-mediated damages in vitro and in vivo. In addition, we have also discussed studies showing that resveratrol can act as a sensitizer to enhance the therapeutic effects of ionizing radiation against cancer cells. Based on available literature, we suggest that resveratrol may be useful for (1) prevention of UVB-mediated damages including skin cancer and (2) enhancing the response of radiation therapies against hyperproliferative, precancerous and neoplastic conditions.

  17. Cell type dependent morphological adaptation in polyelectrolyte hydrogels governs chondrogenic fate.

    Science.gov (United States)

    Raghothaman, Deepak; Leong, Meng Fatt; Lim, Tze Chiun; Wan, Andrew C A; Ser, Zheng; Lee, Eng Hin; Yang, Zheng

    2016-04-04

    Repair of critical-size articular cartilage defects typically involves delivery of cells in biodegradable, 3D matrices. Differences in the developmental status of mesenchymal stem cells (MSCs) and terminally differentiated mature chondrocytes might be a critical factor in engineering appropriate 3D matrices for articular cartilage tissue engineering. This study examined the relationship between material-driven early cell morphological adaptations and chondrogenic outcomes, by studying the influence of aligned collagen type I (Col I) presentation on chondrocytes and MSC in interfacial polyelectrolyte complexation (IPC)-based hydrogels. In the absence of Col I, both chondrocytes and MSCs adopted rounded cell morphology and formed clusters, with chondrocyte clusters favoring the maintenance of hyaline phenotype, while MSC clusters differentiated to fibro-superficial zone-like chondrocytes. Encapsulated chondrocytes in IPC-Col I hydrogel adopted a fibroblastic morphology forming fibro-superficial zone-like phenotype, which could be reversed by inhibiting actin polymerization using cytochalasin D (CytD). In contrast, adoption of fibroblastic morphology by encapsulated MSCs in IPC-Col I facilitated superior chondrogenesis, generating a mature, hyaline neocartilage tissue. CytD treatment abrogated the elongation of MSCs and brought about a single cell-like state, resulting in insignificant chondrogenic differentiation, underscoring the essential requirement of providing matrix environments that are amenable to cell-cell interactions for robust MSC chondrogenic differentiation. Our study demonstrates that MSCs and culture-expanded chondrocytes favour differential microenvironmental niches and emphasizes the importance of designing biomaterials that meet cell type-specific requirements, in adopting chondrocyte or MSC-based approaches for regenerating hyaline, articular cartilage.

  18. Cationic Phosphorus Dendrimer Enhances Photodynamic Activity of Rose Bengal against Basal Cell Carcinoma Cell Lines.

    Science.gov (United States)

    Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2017-05-01

    In the last couple of decades, photodynamic therapy emerged as a useful tool in the treatment of basal cell carcinoma. However, it still meets limitations due to unfavorable properties of photosensitizers such as poor solubility or lack of selectivity. Dendrimers, polymers widely studied in biomedical field, may play a role as photosensitizer carriers and improve the efficacy of photodynamic treatment. Here, we describe the evaluation of an electrostatic complex of cationic phosphorus dendrimer and rose bengal in such aspects as singlet oxygen production, cellular uptake, and phototoxicity against three basal cell carcinoma cell lines. Rose bengal-cationic dendrimer complex in molar ratio 5:1 was compared to free rose bengal. Obtained results showed that the singlet oxygen production in aqueous medium was significantly higher for the complex than for free rose bengal. The cellular uptake of the complex was 2-7-fold higher compared to a free photosensitizer. Importantly, rose bengal, rose bengal-dendrimer complex, and dendrimer itself showed no dark toxicity against all three cell lines. Moreover, we observed that phototoxicity of the complex was remarkably enhanced presumably due to high cellular uptake. On the basis of the obtained results, we conclude that rose bengal-cationic dendrimer complex has a potential in photodynamic treatment of basal cell carcinoma.

  19. Assessment of the pathogenicity of cell-culture-adapted Newcastle disease virus strain Komarov.

    Science.gov (United States)

    Visnuvinayagam, Sivam; Thangavel, K; Lalitha, N; Malmarugan, S; Sukumar, Kuppannan

    2015-01-01

    Newcastle disease vaccines hitherto in vogue are produced from embryonated chicken eggs. Egg-adapted mesogenic vaccines possess several drawbacks such as paralysis and mortality in 2-week-old chicks and reduced egg production in the egg-laying flock. Owing to these possible drawbacks, we attempted to reduce the vaccine virulence for safe vaccination by adapting the virus in a chicken embryo fibroblast cell culture (CEFCC) system. Eighteen passages were carried out by CEFCC, and the pathogenicity was assessed on the basis of the mean death time, intracerebral pathogenicity index, and intravenous pathogenicity index, at equal passage intervals. Although the reduction in virulence demonstrated with increasing passage levels in CEFCC was encouraging, 20% of the 2-week-old birds showed paralytic symptoms with the virus vaccine from the 18(th)(final) passage. Thus, a tissue-culture-adapted vaccine would demand a few more passages by CEFCC in order to achieve a complete reduction in virulence for use as a safe and effective vaccine, especially among younger chicks. Moreover, it can be safely administered even to unprimed 8-week-old birds.

  20. Cytogenetic dose-response and adaptive response in cells of ungulate species exposed to ionizing radiation

    International Nuclear Information System (INIS)

    Ulsh, B.A.; Miller, S.M.; Mallory, F.F.; Mitchel, R.E.J.; Morrison, D.P.; Boreham, D.R.

    2004-01-01

    In the studies reported here, the micronucleus assay, a common cytogenetic technique, was used to examine the dose-responses in fibroblasts from three ungulate species (white-tailed deer, woodland caribou, and Indian muntjac) exposed to high doses of ionizing radiation (1-4 Gy of 60 Co gamma radiation). This assay was also used to examine the effects of exposure to low doses (1-100 mGy) typical of what these species experience in a year from natural and anthropogenic environmental sources. An adaptive response, defined as the induction of resistance to a stressor by a prior exposure to a small 'adapting' stress, was observed after exposure to low doses. This work indicates that very small doses are protective for the endpoint examined. The same level of protection was seen at all adapting doses, including 1 radiation track per cell, the lowest possible cellular dose. These results are consistent with other studies in a wide variety of organisms that demonstrate a protective effect of low doses at both cellular and whole-organism levels. This implies that environmental regulations predicated on the idea that even the smallest dose of radiation carries a quantifiable risk of direct adverse consequences to the exposed organism require further examination. Cytogenetic assays provide affordable and feasible biological effects-based alternatives that are more biologically relevant than traditional contaminant concentration-based radioecological risk assessment

  1. Cth2 Protein Mediates Early Adaptation of Yeast Cells to Oxidative Stress Conditions.

    Directory of Open Access Journals (Sweden)

    Laia Castells-Roca

    Full Text Available Cth2 is an mRNA-binding protein that participates in remodeling yeast cell metabolism in iron starvation conditions by promoting decay of the targeted molecules, in order to avoid excess iron consumption. This study shows that in the absence of Cth2 immediate upregulation of expression of several of the iron regulon genes (involved in high affinity iron uptake and intracellular iron redistribution upon oxidative stress by hydroperoxide is more intense than in wild type conditions where Cth2 is present. The oxidative stress provokes a temporary increase in the levels of Cth2 (itself a member of the iron regulon. In such conditions Cth2 molecules accumulate at P bodies-like structures when the constitutive mRNA decay machinery is compromised. In addition, a null Δcth2 mutant shows defects, in comparison to CTH2 wild type cells, in exit from α factor-induced arrest at the G1 stage of the cell cycle when hydroperoxide treatment is applied. The cell cycle defects are rescued in conditions that compromise uptake of external iron into the cytosol. The observations support a role of Cth2 in modulating expression of diverse iron regulon genes, excluding those specifically involved in the reductive branch of the high-affinity transport. This would result in immediate adaptation of the yeast cells to an oxidative stress, by controlling uptake of oxidant-promoting iron cations.

  2. A model of human nasal epithelial cells adapted for direct and repeated exposure to airborne pollutants.

    Science.gov (United States)

    Bardet, Gaëlle; Achard, Sophie; Loret, Thomas; Desauziers, Valérie; Momas, Isabelle; Seta, Nathalie

    2014-08-17

    Airway epithelium lining the nasal cavity plays a pivotal role in respiratory tract defense and protection mechanisms. Air pollution induces alterations linked to airway diseases such as asthma. Only very few in vitro studies to date have succeeded in reproducing physiological conditions relevant to cellular type and chronic atmospheric pollution exposure. We therefore, set up an in vitro model of human Airway Epithelial Cells of Nasal origin (hAECN) close to real human cell functionality, specifically adapted to study the biological effects of exposure to indoor gaseous pollution at the environmental level. hAECN were exposed under air-liquid interface, one, two, or three-times at 24 h intervals for 1 h, to air or formaldehyde (200 μg/m(3)), an indoor air gaseous pollutant. All experiments were ended at day 4, when both cellular viability and cytokine production were assessed. Optimal adherence and confluence of cells were obtained 96 h after cell seeding onto collagen IV-precoated insert. Direct and repeated exposure to formaldehyde did not produce any cellular damage or IL-6 production change, although weak lower IL-8 production was observed only after the third exposure. Our model is significantly better than previous ones due to cell type and the repeated exposure protocol. Copyright © 2014. Published by Elsevier Ireland Ltd.

  3. Traffic-Adaptive and Energy-Efficient Small Cell Networks-Energy, Delay and Throughput

    OpenAIRE

    Nazrul Alam, Mirza

    2016-01-01

    The low power small cell network has emerged as a promising and feasible solution to address the massive wireless traffic resulting from the aggressive growth of wireless applications. It is also estimated that Internet of things (IoT) will consist of around 50 billion physical objects by 2020. As a result, besides capacity enhancement, other challenges, e.g., energy efficiency, dynamic addressing of UL/DL traffic asymmetry, low latency, multi-hop communications, reliability and coverage have...

  4. The interaction between regulatory T cells and NKT cells in the liver: a CD1d bridge links innate and adaptive immunity.

    Science.gov (United States)

    Hua, Jing; Liang, Shuwen; Ma, Xiong; Webb, Tonya J; Potter, James P; Li, Zhiping

    2011-01-01

    Regulatory T cells (Tregs) and natural killer T (NKT) cells are two distinct lymphocyte subsets that independently regulate hepatic adaptive and innate immunity, respectively. In the current study, we examine the interaction between Tregs and NKT cells to understand the mechanisms of cross immune regulation by these cells. The frequency and function of Tregs were evaluated in wild type and NKT cell deficient (CD1dko) mice. In vitro lymphocyte proliferation and apoptosis assays were performed with NKT cells co-cultured with Tregs. The ability of Tregs to inhibit NKT cells in vivo was examined by adoptive transfer of Tregs in a model of NKT cell mediated hepatitis. CD1dko mice have a significant reduction in hepatic Tregs. Although, the Tregs from CD1dko mice remain functional and can suppress conventional T cells, their ability to suppress activation induced NKT cell proliferation and to promote NKT cell apoptosis is greatly diminished. These effects are CD1d dependent and require cell to cell contact. Adoptive transfer of Tregs inhibits NKT cell-mediated liver injury. NKT cells promote Tregs, and Tregs inhibit NKT cells in a CD1d dependent manner requiring cell to cell contact. These cross-talk immune regulations provide a linkage between innate and adaptive immunity.

  5. Combination of doxorubicin and low-intensity ultrasound causes a synergistic enhancement in cell killing and an additive enhancement in apoptosis induction in human lymphoma U937 cells.

    Science.gov (United States)

    Yoshida, Toru; Kondo, Takashi; Ogawa, Ryohei; Feril, Loreto B; Zhao, Qing-Li; Watanabe, Akihiko; Tsukada, Kazuhiro

    2008-04-01

    Potential clinical use of ultrasound (US) in enhancing the effects of anticancer drugs in the treatment of cancers has been highlighted in previous reports. Increased uptake of drugs by the cancer cells due to US has been suggested as a mechanism. However, the precise mechanism of the enhancement has not yet been elucidated. Here, the combined effects of low-intensity pulsed US and doxorubicin (DOX) on cell killing and apoptosis induction of U937 cells, and mechanisms involved were investigated. Human myelomonocytic lymphoma U937 cells were used for the experiments. Experiments were conducted in 4 groups: (1) non-treated, (2) DOX treated (DOX), (3) US treated (US), and (4) combined (DOX + US). In DOX +US, cells were exposed to 5 microM DOX for 30 min and sonicated by 1 MHz pulsed US (PRF 100 Hz, DF 10%) at intensities of 0.2-0.5 W/cm(2) for 60 s. The cells were washed and incubated for 6 h. The viability was evaluated by Trypan blue dye exclusion test and apoptosis and incorporation of DOX was assessed by flow cytometry. Involvement of sonoporation in molecular incorporation was evaluated using FITC-dextran, hydroxyl radical formation was measured by electron paramagnetic resonance-spin trapping, membrane alteration including lipid peroxidation and membrane fluidity by DOX was evaluated using cis-parinaric acid and perylene fluorescence polarization method, respectively. Synergistic enhancement in cell killing and additive enhancement in induction of apoptosis were observed at and above 0.3 W/cm(2). No enhancement was observed at 0.2 W/cm(2) in cell killing and induction of apoptosis. Hydroxyl radicals formation was detected at and above 0.3 W/cm(2). The radicals were produced more in the DOX + US than US alone. Incorporation of DOX was increased 13% in DOX + US (vs. DOX) at 0.5 W/cm(2). Involvement of sonoporation for increase of drug uptake was suggested by experiment using FITC-labeled dextran. We made the hypothesis that DOX treatment made the cells weaken

  6. Rac1 recruits the adapter protein CMS/CD2AP to cell-cell contacts

    NARCIS (Netherlands)

    van Duijn, Trynette J.; Anthony, Eloise C.; Hensbergen, Paul J.; Deelder, André M.; Hordijk, Peter L.

    2010-01-01

    Rac1 is a member of the Rho family of small GTPases, which regulate cell adhesion and migration through their control of the actin cytoskeleton. Rho-GTPases are structurally very similar, with the exception of a hypervariable domain in the C terminus. Using peptide-based pulldown assays in

  7. Accessible bioprinting: adaptation of a low-cost 3D-printer for precise cell placement and stem cell differentiation.

    Science.gov (United States)

    Reid, John A; Mollica, Peter A; Johnson, Garett D; Ogle, Roy C; Bruno, Robert D; Sachs, Patrick C

    2016-06-07

    The precision and repeatability offered by computer-aided design and computer-numerically controlled techniques in biofabrication processes is quickly becoming an industry standard. However, many hurdles still exist before these techniques can be used in research laboratories for cellular and molecular biology applications. Extrusion-based bioprinting systems have been characterized by high development costs, injector clogging, difficulty achieving small cell number deposits, decreased cell viability, and altered cell function post-printing. To circumvent the high-price barrier to entry of conventional bioprinters, we designed and 3D printed components for the adaptation of an inexpensive 'off-the-shelf' commercially available 3D printer. We also demonstrate via goal based computer simulations that the needle geometries of conventional commercially standardized, 'luer-lock' syringe-needle systems cause many of the issues plaguing conventional bioprinters. To address these performance limitations we optimized flow within several microneedle geometries, which revealed a short tapered injector design with minimal cylindrical needle length was ideal to minimize cell strain and accretion. We then experimentally quantified these geometries using pulled glass microcapillary pipettes and our modified, low-cost 3D printer. This systems performance validated our models exhibiting: reduced clogging, single cell print resolution, and maintenance of cell viability without the use of a sacrificial vehicle. Using this system we show the successful printing of human induced pluripotent stem cells (hiPSCs) into Geltrex and note their retention of a pluripotent state 7 d post printing. We also show embryoid body differentiation of hiPSC by injection into differentiation conducive environments, wherein we observed continuous growth, emergence of various evaginations, and post-printing gene expression indicative of the presence of all three germ layers. These data demonstrate an

  8. Production of infectious genotype 1b virus particles in cell culture and impairment by replication enhancing mutations.

    Directory of Open Access Journals (Sweden)

    Thomas Pietschmann

    2009-06-01

    Full Text Available With the advent of subgenomic hepatitis C virus (HCV replicons, studies of the intracellular steps of the viral replication cycle became possible. These RNAs are capable of self-amplification in cultured human hepatoma cells, but save for the genotype 2a isolate JFH-1, efficient replication of these HCV RNAs requires replication enhancing mutations (REMs, previously also called cell culture adaptive mutations. These mutations cluster primarily in the central region of non-structural protein 5A (NS5A, but may also reside in the NS3 helicase domain or at a distinct position in NS4B. Most efficient replication has been achieved by combining REMs residing in NS3 with distinct REMs located in NS4B or NS5A. However, in spite of efficient replication of HCV genomes containing such mutations, they do not support production of infectious virus particles. By using the genotype 1b isolate Con1, in this study we show that REMs interfere with HCV assembly. Strongest impairment of virus formation was found with REMs located in the NS3 helicase (E1202G and T1280I as well as NS5A (S2204R, whereas a highly adaptive REM in NS4B still allowed virus production although relative levels of core release were also reduced. We also show that cells transfected with the Con1 wild type genome or the genome containing the REM in NS4B release HCV particles that are infectious both in cell culture and in vivo. Our data provide an explanation for the in vitro and in vivo attenuation of cell culture adapted HCV genomes and may open new avenues for the development of fully competent culture systems covering the therapeutically most relevant HCV genotypes.

  9. Ionizing radiation enhances immunogenicity of cells expressing a tumor-specific T-cell epitope

    International Nuclear Information System (INIS)

    Ciernik, Ilja F.; Romero, Pedro; Berzofsky, Jay A.; Carbone, David P.

    1999-01-01

    Background: p53 point mutations represent potential tumor-specific cytolytic T lymphocyte (CTL) epitopes. Whether ionizing radiation (IR) alters the immunological properties of cells expressing mutant p53 in respect of the CTL epitope generated by a defined point mutation has not been evaluated. Methods: Mutant p53-expressing syngeneic, nontumor forming BALB/c 3T3 fibroblasts, tumor forming ras-transfected BALB/c 3T3 sarcomas, and DBA/2-derived P815 mastocytoma cells, which differ at the level of minor histocompatibility antigens, were used as cellular vaccines. Cells were either injected with or without prior IR into naive BALB/c mice. Cellular cytotoxicity was assessed after secondary restimulation of effector spleen cells in vitro. Results: Injection of P815 mastocytoma cells expressing the mutant p53 induced mutation-specific CTL in BALB/c mice irrespective of prior irradiation. However, syngeneic fibroblasts or fibrosarcomas endogenously expressing mutant p53 were able to induce significant mutation-specific CTL only when irradiated prior to injection into BALB/c mice. IR of fibroblasts did not detectably alter the expression of cell surface molecules involved in immune response induction, nor did it alter the short-term in vitro viability of the fibroblasts. Interestingly, radioactively-labeled fibroblasts injected into mice after irradiation showed altered organ distribution, suggesting that the in vivo fate of these cells may play a crucial role in their immunogenicity. Conclusions: These findings indicate that IR can alter the immunogenicity of syngeneic normal as well as tumor forming fibroblasts in vivo, and support the view that ionizing radiation enhances immunogenicity of cellular tumor vaccines

  10. Double-chimera proteins to enhance recruitment of endothelial cells and their progenitor cells.

    Science.gov (United States)

    Behjati, M; Kazemi, M; Hashemi, M; Zarkesh-Esfahanai, S H; Bahrami, E; Hashemi-Beni, B; Ahmadi, R

    2013-08-20

    Enhanced attraction of selective vascular reparative cells is of great importance in order to increase vascular patency after endovascular treatments. We aimed to evaluate efficient attachment of endothelial cells and their progenitors on surfaces coated with mixture of specific antibodies, L-selectin and VE-cadherin, with prohibited platelet attachment. The most efficient conditions for coating of L-selectin-Fc chimera and VE-cadherin-Fc chimera proteins were first determined by protein coating on ELISA plates. The whole processes were repeated on titanium substrates, which are commonly used to coat stents. Endothelial progenitor cells (EPCs) and human umbilical vein endothelial cells (HUVECs) were isolated and characterized by flow cytometry. Cell attachment, growth, proliferation, viability and surface cytotoxicity were evaluated using nuclear staining and MTT assay. Platelet and cell attachment were evaluated using scanning electron microscopy. Optimal concentration of each protein for surface coating was 50 ng/ml. The efficacy of protein coating was both heat and pH independent. Calcium ions had significant impact on simultaneous dual-protein coating (P<0.05). Coating stability data revealed more than one year stability for these coated proteins at 4°C. L-selectin and VE-cadherin (ratio of 50:50) coated surface showed highest EPC and HUVEC attachment, viability and proliferation compared to single protein coated and non-coated titanium surfaces (P<0.05). This double coated surface did not show any cytotoxic effect. Surfaces coated with L-selectin and VE-cadherin are friendly surface for EPC and endothelial cell attachment with less platelet attachment. These desirable factors make the L-selectin and VE-cadherin coated surfaces perfect candidate endovascular device. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Nanograting-based plasmon enhancement for total internal reflection fluorescence microscopy of live cells

    International Nuclear Information System (INIS)

    Kim, Kyujung; Cho, Eun-Jin; Suh, Jin-Suck; Huh, Yong-Min; Kim, Donghyun; Kim, Dong Jun

    2009-01-01

    We investigated evanescent field enhancement based on subwavelength nanogratings for improved sensitivity in total internal reflection microscopy of live cells. The field enhancement is associated with subwavelength-grating-coupled plasmon excitation. An optimum sample employed a silver grating on a silver film and an SF10 glass substrate. Field intensity was enhanced by approximately 90% when measured by fluorescent excitation of microbeads relative to that on a bare prism as a control, which is in good agreement with numerical results. The subwavelength-grating-mediated field enhancement was also applied to live cell imaging of quantum dots, which confirmed the sensitivity enhancement qualitatively.

  12. Disruption of cell walls for enhanced lipid recovery

    Science.gov (United States)

    Knoshaug, Eric P; Donohoe, Bryon S; Gerken, Henri; Laurens, Lieve; Van Wychen, Stefanie Rose

    2015-03-24

    Presented herein are methods of using cell wall degrading enzymes for recovery of internal lipid bodies from biomass sources such as algae. Also provided are algal cells that express at least one exogenous gene encoding a cell wall degrading enzyme and methods for recovering lipids from the cells.

  13. Adaptive tuning of a 2DOF controller for robust cell manipulation using IPMC actuators

    International Nuclear Information System (INIS)

    McDaid, A J; Aw, K C; Haemmerle, E; Xie, S Q; Shahinpoor, M

    2011-01-01

    Rapid advancement in medicine and bioscience is causing demand for faster, more accurate and dexterous as well as safer and more reliable micro-manipulators capable of handling biological cells. Current micro-manipulation techniques commonly damage cell walls and membranes due to their stiffness and rigidity. Ionic polymer-metal composite (IPMC) actuators have inherent compliance and with their ability to operate well in fluid and cellular environments they present a unique solution for safe cell manipulation. The reason for the downfall of IPMCs is that their complex behaviour makes them hard to control precisely in unknown environments and in the presence of sizeable external disturbances. This paper presents a novel scheme for adaptively tuning IPMC actuators for precise and robust micro-manipulation of biological cells. A two-degree-of-freedom (2DOF) controller is developed to allow optimal performance for both disturbance rejection (DR) and set point (SP) tracking. These criteria are optimized using a proposed IFT algorithm which adaptively updates the controller parameters, with no model or prior knowledge of the operating conditions, to achieve a compliant manipulation system which can precisely track targets in the presence of large external disturbances, as will be encountered in real biological environments. Experiments are presented showing the performance optimization of an IPMC actuator in the presence of external mechanical disturbances as well as the optimization of the SP tracking. The IFT algorithm successfully tunes the DR and SP to an 85% and 69% improvement, respectively. Results are also presented for a one-degree-of-freedom (1DOF) controller tuned first for DR and then for SP, for a comparison with the 2DOF controller. Validation has been undertaken to verify that the 2DOF controller does indeed outperform both 1DOF controllers over a variety of operating conditions.

  14. Adaptive Intervention Design in Mobile Health: Intervention Design and Development in the Cell Phone Intervention for You (CITY) Trial

    Science.gov (United States)

    Lin, Pao-Hwa; Intille, Stephen; Bennett, Gary; Bosworth, Hayden B; Corsino, Leonor; Voils, Corrine; Grambow, Steven; Lazenka, Tony; Batch, Bryan C; Tyson, Crystal; Svetkey, Laura P

    2015-01-01

    Background/Aims The obesity epidemic has spread to young adults, and obesity is a significant risk factor for cardiovascular disease. The prominence and increasing functionality of mobile phones may provide an opportunity to deliver longitudinal and scalable weight management interventions in young adults. The aim of this manuscript is to describe the design and development of the intervention tested in the Cell Phone Intervention for You (CITY) study and to highlight the importance of adaptive intervention design (AID) that made it possible. The CITY study was an NHLBI-sponsored, controlled 24-month randomized clinical trial (RCT) comparing two active interventions to a usual-care control group. Participants were 365 overweight or obese (BMI ≥ 25 kg/m2) young adults. Methods Both active interventions were designed based on social cognitive theory and incorporated techniques for behavioral self-management and motivational enhancement. Initial intervention development occurred during a 1-year formative phase utilizing focus groups and iterative, participatory design. During the intervention testing, AID, where an intervention is updated or extended throughout a trial while assuring the delivery of exactly the same intervention to each cohort, was employed. The AID strategy distributed technical work and allowed introduction of novel components in phases intended to help promote and sustain participant engagement. AID was made possible by exploiting the mobile phone's remote data capabilities so that adoption of particular application components could be continuously monitored and components subsequently added or updated remotely. Results The cellphone intervention was delivered almost entirely via cell phone and was always-present, proactive, and interactive – providing passive and active reminders, frequent opportunities for knowledge dissemination, and multiple tools for self-tracking and receiving tailored feedback. The intervention changed over two years to

  15. Participation of intercellular communication and intracellular signal transduction in the radio-adaptive response of human fibroblastic cells

    International Nuclear Information System (INIS)

    Ishii, Keiichiro; Hoshi, Yuko; Iwasaki, Toshiyasu; Watanabe, Masami

    1997-01-01

    To investigate the radio-adaptive response of normal cells to low-dose radiation, we irradiated human embryonic cells with low-dose X-rays and examined the changes in sensitivity to subsequent high-dose X-irradiation. When the cells were irradiated by 200 cGy, the growth ratio of the viable cells five days after the irradiation decreased to 37% of that of the cells which received no X-irradiation. When the cells received a conditioning irradiation of 10 to 20 cGy four hours before the irradiation of 200 cGy, the growth ratio increased significantly to 45-53%, and a peak was reached at a conditioning dose of 13 cGy. Cells blocked off intercellular communication either in Ca 2+ ion-free medium or in TPA added medium during the conditioning irradiation of 13 cGy did not show the improvement of growth ratio. Addition of H-7, as an inhibitor of PKC, to the medium during the conditioning irradiation inhibited the induction of the radio-adaptive response. However, addition of either inhibitor of A kinase, H-89, or inhibitor of G kinase, H-8, failed to inhibit the induction of the radio-adaptive response. These results suggest that: (1) normal cells show an adaptive response to low-dose radiation, (2) intercellular communication may play a role in radio-adaptive responses, (3) the transduction of the signal induced in cells by low-dose X-irradiation via protein kinase C was involved in radio-adaptive responses, not via A kinase nor G kinase. (author)

  16. Evolution of vertebrate adaptive immunity: immune cells and tissues, and AID/APOBEC cytidine deaminases.

    Science.gov (United States)

    Hirano, Masayuki

    2015-08-01

    All surviving jawed vertebrate representatives achieve diversity in immunoglobulin-based B and T cell receptors for antigen recognition through recombinatorial rearrangement of V(D)J segments. However, the extant jawless vertebrates, lampreys and hagfish, instead generate three types of variable lymphocyte receptors (VLRs) through a template-mediated combinatorial assembly of different leucine-rich repeat (LRR) sequences. The clonally diverse VLRB receptors are expressed by B-like lymphocytes, while the VLRA and VLRC receptors are expressed by lymphocyte lineages that resemble αβ and γδ T lymphocytes, respectively. These findings suggest that three basic types of lymphocytes, one B-like and two T-like, are an essential feature of vertebrate adaptive immunity. Around 500 million years ago, a common ancestor of jawed and jawless vertebrates evolved a genetic program for the development of prototypic lymphoid cells as a foundation for an adaptive immune system. This acquisition preceded the convergent evolution of alternative types of clonally diverse receptors for antigens in all vertebrates, as reviewed in this article. © 2015 WILEY Periodicals, Inc.

  17. Trp53 activity is repressed in radio-adapted cultured murine limb bud cells

    International Nuclear Information System (INIS)

    Vares, Guillaume; Wang, Bing; Tanaka, Kaoru; Shang, Yi; Fujita, Kazuko; Hayata, Isamu; Nenoi, Mitsuru

    2011-01-01

    Understanding the effects of ionizing radiation (IR) at low dose in fetal models is of great importance, because the fetus is considered to be at the most radiosensitive stage of the development and prenatal radiation might influence subsequent development. We previously demonstrated the existence of an adaptive response (AR) in murine fetuses after pre-exposure to low doses of X-rays. Trp53-dependent apoptosis was suggested to be responsible for the teratogenic effects of IR; decreased apoptosis was observed in adapted animals. In this study, in order to investigate the role of Trp53 in AR, we developed a new model of irradiated micromass culture of fetal limb bud cells, which replicated proliferation, differentiation and response to IR in murine embryos. Murine fetuses were exposed to whole-body priming irradiation of 0.3 Gy or 0.5 Gy at embryonic day 11 (E11). Limb bud cells (collected from digital ray areas exhibiting radiation-induced apoptosis) were cultured and exposed to a challenging dose of 4 Gy at E12 equivalent. The levels of Trp53 protein and its phosphorylated form at Ser18 were investigated. Our results suggested that the induction of AR in mouse embryos was correlated with a repression of Trp53 activity. (author)

  18. Blocking junctional adhesion molecule C enhances dendritic cell migration and boosts the immune responses against Leishmania major.

    Directory of Open Access Journals (Sweden)

    Romain Ballet

    2014-12-01

    Full Text Available The recruitment of dendritic cells to sites of infections and their migration to lymph nodes is fundamental for antigen processing and presentation to T cells. In the present study, we showed that antibody blockade of junctional adhesion molecule C (JAM-C on endothelial cells removed JAM-C away from junctions and increased vascular permeability after L. major infection. This has multiple consequences on the output of the immune response. In resistant C57BL/6 and susceptible BALB/c mice, we found higher numbers of innate immune cells migrating from blood to the site of infection. The subsequent migration of dendritic cells (DCs from the skin to the draining lymph node was also improved, thereby boosting the induction of the adaptive immune response. In C57BL/6 mice, JAM-C blockade after L. major injection led to an enhanced IFN-γ dominated T helper 1 (Th1 response with reduced skin lesions and parasite burden. Conversely, anti JAM-C treatment increased the IL-4-driven T helper 2 (Th2 response in BALB/c mice with disease exacerbation. Overall, our results show that JAM-C blockade can finely-tune the innate cell migration and accelerate the consequent immune response to L. major without changing the type of the T helper cell response.

  19. Enhancement of Mucosal Immunogenicity of Viral Vectored Vaccines by the NKT Cell Agonist Alpha-Galactosylceramide as Adjuvant

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    2014-10-01

    Full Text Available Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer, a synthetic glycolipid agonist of natural killer T (NKT cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors.

  20. A novel ship CFAR detection algorithm based on adaptive parameter enhancement and wake-aided detection in SAR images

    Science.gov (United States)

    Meng, Siqi; Ren, Kan; Lu, Dongming; Gu, Guohua; Chen, Qian; Lu, Guojun

    2018-03-01

    Synthetic aperture radar (SAR) is an indispensable and useful method for marine monitoring. With the increase of SAR sensors, high resolution images can be acquired and contain more target structure information, such as more spatial details etc. This paper presents a novel adaptive parameter transform (APT) domain constant false alarm rate (CFAR) to highlight targets. The whole method is based on the APT domain value. Firstly, the image is mapped to the new transform domain by the algorithm. Secondly, the false candidate target pixels are screened out by the CFAR detector to highlight the target ships. Thirdly, the ship pixels are replaced by the homogeneous sea pixels. And then, the enhanced image is processed by Niblack algorithm to obtain the wake binary image. Finally, normalized Hough transform (NHT) is used to detect wakes in the binary image, as a verification of the presence of the ships. Experiments on real SAR images validate that the proposed transform does enhance the target structure and improve the contrast of the image. The algorithm has a good performance in the ship and ship wake detection.

  1. Enhancing and Adapting Treatment Foster Care: Lessons Learned in Trying to Change Practice.

    Science.gov (United States)

    Murray, Maureen M; Southerland, Dannia; Farmer, Elizabeth M; Ballentine, Kess

    2010-01-01

    Evidence-based practices to improve outcomes for children with severe behavioral and emotional problems have received a great deal of attention in children's mental health. Therapeutic Foster Care (TFC), a residential intervention for youth with emotional or behavioral problems, is one of the few community-based programs that is considered to be evidence-based. However, as for most treatment approaches, the vast majority of existing programs do not deliver the evidence-based version. In an attempt to fill this gap and improve practice across a wide range of TFC agencies, we developed an enhanced model of TFC based on input from both practice and research. It includes elements associated with improved outcomes for youth in "usual care" TFC agencies as well as key elements from Chamberlain's evidence-based model. The current manuscript describes this "hybrid" intervention - Together Facing the Challenge - and discusses key issues in implementation. We describe the sample and settings, highlight key implementation strategies, and provide "lessons learned" to help guide others who may wish to change practice in existing agencies.

  2. Adaptive Transmitter Optimization in Multiuser Multiantenna Systems: Theoretical Limits, Effect of Delays, and Performance Enhancements

    Directory of Open Access Journals (Sweden)

    Samardzija Dragan

    2005-01-01

    Full Text Available The advances in programmable and reconfigurable radios have rendered feasible transmitter optimization schemes that can greatly improve the performance of multiple-antenna multiuser systems. Reconfigurable radio platforms are particularly suitable for implementation of transmitter optimization at the base station. We consider the downlink of a wireless system with multiple transmit antennas at the base station and a number of mobile terminals (i.e., users each with a single receive antenna. Under an average transmit power constraint, we consider the maximum achievable sum data rates in the case of (1 zero-forcing (ZF spatial prefilter, (2 modified zero-forcing (MZF spatial prefilter, and (3 triangularization spatial prefilter coupled with dirty-paper coding (DPC transmission scheme. We show that the triangularization with DPC approaches the closed-loop MIMO rates (upper bound for higher SNRs. Further, the MZF solution performs very well for lower SNRs, while for higher SNRs, the rates for the ZF solution converge to the MZF rates. An important impediment that degrades the performance of such transmitter optimization schemes is the delay in channel state information (CSI. We characterize the fundamental limits of performance in the presence of delayed CSI and then propose performance enhancements using a linear MMSE predictor of the CSI that can be used in conjunction with transmitter optimization in multiple-antenna multiuser systems.

  3. Gas composition modeling in a reformed Methanol Fuel Cell system using adaptive Neuro-Fuzzy Inference Systems

    DEFF Research Database (Denmark)

    Justesen, Kristian Kjær; Andreasen, Søren Juhl; Shaker, Hamid Reza

    2013-01-01

    This work presents a method for modeling the gas composition in a Reformed Methanol Fuel Cell system. The method is based on Adaptive Neuro-Fuzzy-Inference-Systems which are trained on experimental data. The developed models are of the H2, CO2, CO and CH3OH mass flows of the reformed gas. The ANFIS......, or fuel cell diagnostics systems....

  4. Cell culture adaptation mutations in foot-and-mouth disease virus serotype A capsid proteins: implications for receptor interactions

    Science.gov (United States)

    In this study we describe the adaptive changes fixed on the capsid of several foot-and-mouth disease virus serotype A strains during propagation in cell monolayers. Viruses passaged extensively in three cell lines (BHK-21, LFBK and IB-RS-2), consistently gained several positively charged amino acids...

  5. Hyperthermia enhances radiosensitivity of colorectal cancer cells through ROS inducing autophagic cell death.

    Science.gov (United States)

    Ba, Ming-Chen; Long, Hui; Wang, Shuai; Wu, Yin-Bing; Zhang, Bo-Huo; Yan, Zhao-Fei; Yu, Fei-Hong; Cui, Shu-Zhong

    2018-04-01

    Hyperthermia (HT) enhances the anti-cancer effects of radiotherapy (RT), but the precise biochemical mechanisms involved are unclear. This study was aim to investigate if mild HT sensitizes colorectal cancer cells to RT through reactive oxygen species (ROS)-inducing autophagic cell death in a mice model of HCT116 human colorectal cancer. HCT116 mice model were randomly divided into five groups: mock group, hyperthermia group (HT), radiotherapy group (RT), HT + RT group, and HT + RT +N-acetyl L-cysteine (NAC) group (HT + CT + NAC). After four weeks of treatment, cancer growth inhibition, rate and mitochondrial membrane potential were measured with MTT and JC-1 assays, respectively, while ROS were estimated fluorimetrically. The relationship of these parameters to expressions of autophagy-related genes Beclin1, LC3B, and mTOR was analyzed. Gene expression was measured by Real-Time polymerase chain reaction (RT-PCR). There were significant increases in ROS levels and mitochondrial membrane potential in the HT + RT group. ROS levels in the HT + RT group increased more significantly than in any other group. In contrast, ROS levels in the HT + RT + NAC group were significantly decreased relative to the HT + RT group. The number of autophagic bodies in HT + RT group was higher than that of mock group. There were significant increases in the expression of Beclin1 and LC3B genes, while mTOR expression was significantly decreased in the HT + CT group. Treatment with NAC reversed the pattern of these changes. These results indicate that HT enhances the radiosensitivity of colorectal cancer cells to RT through ROS inducing autophagic cell death. © 2017 Wiley Periodicals, Inc.

  6. Sensitization of gastric cancer cells to alkylating agents by glaucocalyxin B via cell cycle arrest and enhanced cell death.

    Science.gov (United States)

    Ur Rahman, Muhammad Saif; Zhang, Ling; Wu, Lingyan; Xie, Yuqiong; Li, Chunchun; Cao, Jiang

    2017-01-01

    Severe side effects are major problems with chemotherapy of gastric cancer (GC). These side effects can be reduced by using sensitizing agents in combination with therapeutic drugs. In this study, the low/nontoxic dosage of glaucocalyxin B (GLB) was used with other DNA linker agents mitomycin C (MMC), cisplatin (DDP), or cyclophosphamide (CTX) to treat GC cells. Combined effectiveness of GLB with drugs was determined by proliferation assay. The molecular mechanisms associated with cell proliferation, migration, invasion, cell cycle, DNA repair/replication, apoptosis, and autophagy were investigated by immunoblotting for key proteins involved. Cell cycle and apoptosis analysis were performed by flow cytometry. Reactive oxygen species level was also examined for identification of its role in apoptosis. Proliferation assay revealed that the addition of 5 µM GLB significantly sensitizes gastric cancer SGC-7901 cells to MMC, DDP, and CTX by decreasing half-maximal inhibitory concentration (IC 50 ) by up to 75.40%±5%, 45.10%±5%, and 52.10%±5%, respectively. GLB + drugs decreased the expression level of proteins involved in proliferation and migration, suggesting the anticancer potential of GLB + drugs. GLB + MMC, GLB + CTX, and GLB + DDP arrest the cells in G 0 /G 1 and G 1 /S phase, respectively, which may be the consequence of significant decrease in the level of enzymes responsible for DNA replication and telomerase shortening. Combined use of GLB with these drugs also induces DNA damage and apoptosis by activating caspase/PARP pathways and increased production of reactive oxygen species and increased autophagy in GC cells. GLB dosage sensitizes GC cells to the alkylating agents via arresting the cell cycle and enhancing cell death. This is of significant therapeutic importance in the reduction of side effects associated with these drugs.

  7. Enhanced Radiosensitivity of Tumor Cells Treated with Vanadate in Vitro

    International Nuclear Information System (INIS)

    Lee, Myung Za; Lee, Won Young

    1994-01-01

    Intracellular ions which have a major role in cellular function have been reported to affect repair of radiation damage. Recently it has been reported that ouabain sensitizes A549 tumor cells hut not CCL-120 normal cells to radiation. Ouabain inhibits the Na+-K+-pump rapidly thus it increases intracellular Na concentration. Vanadate which is distributed extensively in almost all living organisms in known to be a Na+-K+-ATPase inhibitors. This study was performed to see any change in radiosensitivity of tumor cell by vanadate and any role of Na+-K+-ATPase in radiosensitization. Experiments have been carried out by pretreatment with vanadate in human cell line(A549, JMG) and mouse cell line(L1210, spleen). For the cell survival MTT assay was performed for A549 and JMG cell and trypan blue dye exclusion test for L120, and spleen cells. Measurements of Na+-K+-ATPase activity in control, vanadate treated cell, radiation treated cell (9 Gy for A549 and JMG, 2 Gy for L1201, spleen), and combined 10-6 M vanadate and radiation treated cells were done. The results were summarized as follows. 1. L1210 cell was most radiosensitive, and spleen cell and JMG cell were intermediate, and A549 cell was least radiosensitive. 2. Minimum or cytotoxicity was seen with vanadate below concentration of 10-6 M. 3. In A549 cells there was a little change in radiosensitivity with treatment of vanadate. However radiation sensitization was shown in low dose level of radiation i. E. 2-Gy. In JMG cells no change in radiosensitivity was noted. Both L1210 and spleen cell had radiosensitization but change was greater in tumor cell. 4. Na+-K+-ATPase activity was inhibited significantly in tumor cell by treatment of vanadate. 5. Radiation itself inhibited Na+-K+-ATPase activity of tumor cell with high Na+- K+-ATPase concention. Increase in radiosensitivity by vanadate was closely associated with original Na+-K+-ATPase contents. From the above results vanadate had little cytotoxicity and it sensitized

  8. Electrical pulse – mediated enhanced delivery of silver nanoparticles into living suspension cells for surface enhanced Raman spectroscopy

    International Nuclear Information System (INIS)

    Lin, J; Li, B; Feng, S; Chen, G; Li, Y; Huang, Z; Chen, R; Yu, Y; Huang, H; Lin, S; Li, C; Su, Y; Zeng, H

    2012-01-01

    Electrical pulse-mediated enhanced silver nanoparticles delivery is a much better method for intracellular surface-enhanced Raman spectroscopy (SERS) measurements of suspension cells. Robust and high-quality SERS spectra of living suspension cells were obtained based on an electroporation-SERS method, which can overcomes the shortcoming of non-uniform distribution of silver nanoparticles localized in the cell cytoplasm after electroporation and reduces the amount variance of silver nanoparticles delivered into different cells. The electroporation parameters include three 150 V (375 V/cm) electric pulses of 1, 5, and 5 ms durations respectively. Our results indicate that considerable amount of silver nanoparticles can be rapidly delivered into the human promyelocytic leukemia HL60 cells, and the satisfied SERS spectra were obtained while the viability of the treated cells was highly maintained (91.7%). The electroporation-SERS method offers great potential approach in delivering silver nanoparticles into living suspension cells, which is useful for widely biomedical applications including the real-time intracellular SERS analysis of living cells

  9. Proteomic changes in a childhood acute lymphoblastic leukemia cell line during the adaptation to vincristine.

    Science.gov (United States)

    Guzmán-Ortiz, Ana Laura; Aparicio-Ozores, Gerardo; Valle-Rios, Ricardo; Medina-Contreras, Oscar; Patiño-López, Genaro; Quezada, Héctor

    Relapse occurs in approximately 20% of Mexican patients with childhood acute lymphoblastic leukemia (ALL). In this group, chemoresistance may be one of the biggest challenges. An overview of complex cellular processes like drug tolerance can be achieved with proteomic studies. The B-lineage pediatric ALL cell line CCRF-SB was gradually exposed to the chemotherapeutic vincristine until proliferation was observed at 6nM, control cells were cultured in the absence of vincristine. The proteome from each group was analyzed by nanoHPLC coupled to an ESI-ion trap mass spectrometer. The identified proteins were grouped into overrepresented functional categories with the PANTHER classification system. We found 135 proteins exclusively expressed in the presence of vincristine. The most represented functional categories were: Toll receptor signaling pathway, Ras Pathway, B and T cell activation, CCKR signaling map, cytokine-mediated signaling pathway, and oxidative phosphorylation. Our study indicates that signal transduction and mitochondrial ATP production are essential during adaptation of leukemic cells to vincristine, these processes represent potential therapeutic targets. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  10. Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0380 TITLE: Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias PRINCIPAL...2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias 5b. GRANT NUMBER...leukemias still have poor prognosis, particularly in the elderly, and require hematopoietic cell transplants to fully kill the tumor, which is both

  11. Oxygen enhancement ratios in synchronous HeLa cells exposed to low-LET radiation

    International Nuclear Information System (INIS)

    Sapozink, M.D.

    1977-01-01

    HeLa cells were synchronized by the mitotic selection method and rendered hypoxic by coincubation with an excess of heavily irradiated, but metabolically active, feeder cells. An oxygen enhancement ratio (OER) of about 3 was obtained in interphase HeLa cells irradiated with x or gamma rays. A significantly lower OER was obtained with cells in, or close to, mitosis. The significance of this decrease in the oxygen effect in mitotic cells is discussed

  12. Dimethyloxalylglycine may be enhance the capacity of neural-like cells in treatment of Alzheimer disease.

    Science.gov (United States)

    Ghasemi Moravej, Fahimeh; Vahabian, Mehrangiz; Soleimani Asl, Sara

    2016-06-01

    Although using differentiated stem cells is the best proposed option for the treatment of Alzheimer disease (AD), an efficient differentiation and cell therapy require enhanced cell survival and homing and decreased apoptosis. It seems that hypoxia preconditioning via Dimethyloxalylglycine (DMOG) may increase the capacity of MSC to induce neural like stem cells (NSCs). Furthermore, it can likely improve the viability of NSCs when transplanted into the brain of AD rats. © 2016 International Federation for Cell Biology.

  13. Enhancement of Bleomycin Sensitivity in Human Lung Cancer Cell ...

    African Journals Online (AJOL)

    Methods: The inhibitory effect of bleomycin on A549 cells was determined by incubating the cells for 24 h in different .... also include advantageous psychological effects such as .... cyclooxygenase-2 enzyme inhibitors: A rational advance?

  14. Graphene for enhanced embryonic stem cell photo-transfection efficiency

    CSIR Research Space (South Africa)

    Mthunzi, P

    2013-04-01

    Full Text Available Due to their pluripotency properties, embryonic stem (ES) cells possess great potential in regenerative therapy. Since reported a promising tissue engineering scaffold material, here, graphene is demonstrated to significantly improve the ES cell...

  15. Nano-topography Enhances Communication in Neural Cells Networks

    KAUST Repository

    Onesto, V.; Cancedda, L.; Coluccio, M. L.; Nanni, M.; Pesce, M.; Malara, N.; Cesarelli, M.; Di Fabrizio, Enzo M.; Amato, F.; Gentile, F.

    2017-01-01

    Neural cells are the smallest building blocks of the central and peripheral nervous systems. Information in neural networks and cell-substrate interactions have been heretofore studied separately. Understanding whether surface nano-topography can

  16. Carbonic anhydrase IX inhibition affects viability of cancer cells adapted to extracellular acidosis.

    Science.gov (United States)

    Andreucci, Elena; Peppicelli, Silvia; Carta, Fabrizio; Brisotto, Giulia; Biscontin, Eva; Ruzzolini, Jessica; Bianchini, Francesca; Biagioni, Alessio; Supuran, Claudiu T; Calorini, Lido

    2017-12-01

    Among the players of the adaptive response of cancer cells able to promote a resistant and aggressive phenotype, carbonic anhydrase IX (CAIX) recently has emerged as one of the most relevant drug targets. Indeed, CAIX targeting has received a lot of interest, and selective inhibitors are currently under clinical trials. Hypoxia has been identified as the master inductor of CAIX, but, to date, very few is known about the influence that another important characteristic of tumor microenvironment, i.e., extracellular acidosis, exerts on CAIX expression and activity. In the last decades, acidic microenvironment has been associated with aggressive tumor phenotype endowed with epithelial-to-mesenchymal transition (EMT) profile, high invasive and migratory ability, apoptosis, and drug resistance. We demonstrated that melanoma, breast, and colorectal cancer cells transiently and chronically exposed to acidified medium (pH 6.7 ± 0.1) showed a significantly increased CAIX expression compared to those grown in standard conditions (pH 7.4 ± 0.1). Moreover, we observed that the CAIX inhibitor FC16-670A (also named SLC-0111, which just successfully ended phase I clinical trials) not only prevents such increased expression under acidosis but also promotes apoptotic and necrotic programs only in acidified cancer cells. Thus, CAIX could represent a selective target of acidic cancer cells and FC16-670A inhibitor as a useful tool to affect this aggressive subpopulation characterized by conventional therapy escape. Cancer cells overexpress CAIX under transient and chronic extracellular acidosis. Acidosis-induced CAIX overexpression is NF-κB mediated and HIF-1α independent. FC16-670A prevents CAIX overexpression and induces acidified cancer cell death.

  17. Dermal regulatory T cells display distinct migratory behavior that is modulated during adaptive and innate inflammation.

    Science.gov (United States)

    Chow, Zachary; Mueller, Scott N; Deane, James A; Hickey, Michael J

    2013-09-15

    Regulatory T cells (Tregs) are important in controlling skin inflammation, an effect dependent on their ability to home to this organ. However, little is known regarding their behavior in the skin. In this study, we used multiphoton imaging in Foxp3-GFP mice to examine the behavior of endogenous Tregs in resting and inflamed skin. Although Tregs were readily detectable in the uninflamed dermis, most were nonmotile. Induction of contact sensitivity increased the proportion of motile Tregs, and also induced Treg recruitment. This response was significantly blunted in mice challenged with an irrelevant hapten, or by inhibition of effector cell recruitment, indicating a role for T cell-dependent inflammation in induction of Treg migration. Moreover, induction of Treg migration was inhibited by local injection of a CCR4 antagonist, indicating a role for CCR4 in this response. Exposure of naive mice to hapten also induced an increase in the proportion of migratory Tregs, demonstrating that innate signals can also induce Treg migration. Simultaneous examination of the migration of CD4⁺ effector cells and Tregs in the same region of uninflamed skin demonstrated that effector cells behaved differently, being uniformly highly migratory. These findings indicate that Treg behavior in skin differs from that of CD4⁺ effector cells, in that only a low proportion of Tregs is migratory under resting conditions. However, in response to both adaptive and innate inflammation, the proportion of migratory Tregs increases, raising the possibility that this response is important in multiple forms of skin inflammation.

  18. Radiation-induced enhancement of enzymatic cell lysis of Micrococcus radiodurans

    International Nuclear Information System (INIS)

    Watanabe, H.; Takehisa, M.; Iizuka, H.

    1981-01-01

    The intact cells of M. radiodurans were rendered sensitive to the action of lytic enzyme (P2-2 enzyme) by irradiation. The radiation-induced enhancement of cell lysis with P2-2 enzyme was completely prevented by the addition of t-butanol and irradiation at liquid nitrogen temperature. These results indicate that the enhancement is due to indirect action resulting from OH radicals. Cell lysis by lysozyme was enhanced only when the cells were irradiated under N 2 O. The enhancement of cell lysis with lysozyme was also prevented by adding alcohols. On the other hand, when lipid components in cells were removed by extraction with n-butanol, the radiation-induced enhancement of cell lysis with P2-2 enzyme and lysozyme was not observed. From these results it is concluded that the enhancement of enzymatic cell lysis by irradiation is attributable to alteration in the lipid-rich layer of the cell wall caused by OH radicals

  19. Radiation-induced enhancement of enzymatic cell lysis of Micrococcus radiodurans

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, H.; Takehisa, M. [Japan Atomic Energy Research Inst., Takasaki, Gunma, Takasaki Radiation Chemistry Research Establishment (Japan); Iizuka, H.

    1981-10-15

    The intact cells of M. radiodurans were rendered sensitive to the action of lytic enzyme (P2-2 enzyme) by irradiation. The radiation-induced enhancement of cell lysis with P2-2 enzyme was completely prevented by the addition of t-butanol and irradiation at liquid nitrogen temperature. These results indicate that the enhancement is due to indirect action resulting from OH radicals. Cell lysis by lysozyme was enhanced only when the cells were irradiated under N{sub 2}O. The enhancement of cell lysis with lysozyme was also prevented by adding alcohols. On the other hand, when lipid components in cells were removed by extraction with n-butanol, the radiation-induced enhancement of cell lysis with P2-2 enzyme and lysozyme was not observed. From these results it is concluded that the enhancement of enzymatic cell lysis by irradiation is attributable to alteration in the lipid-rich layer of the cell wall caused by OH radicals.

  20. Automated Photoreceptor Cell Identification on Nonconfocal Adaptive Optics Images Using Multiscale Circular Voting.

    Science.gov (United States)

    Liu, Jianfei; Jung, HaeWon; Dubra, Alfredo; Tam, Johnny

    2017-09-01

    Adaptive optics scanning light ophthalmoscopy (AOSLO) has enabled quantification of the photoreceptor mosaic in the living human eye using metrics such as cell density and average spacing. These rely on the identification of individual cells. Here, we demonstrate a novel approach for computer-aided identification of cone photoreceptors on nonconfocal split detection AOSLO images. Algorithms for identification of cone photoreceptors were developed, based on multiscale circular voting (MSCV) in combination with a priori knowledge that split detection images resemble Nomarski differential interference contrast images, in which dark and bright regions are present on the two sides of each cell. The proposed algorithm locates dark and bright region pairs, iteratively refining the identification across multiple scales. Identification accuracy was assessed in data from 10 subjects by comparing automated identifications with manual labeling, followed by computation of density and spacing metrics for comparison to histology and published data. There was good agreement between manual and automated cone identifications with overall recall, precision, and F1 score of 92.9%, 90.8%, and 91.8%, respectively. On average, computed density and spacing values using automated identification were within 10.7% and 11.2% of the expected histology values across eccentricities ranging from 0.5 to 6.2 mm. There was no statistically significant difference between MSCV-based and histology-based density measurements (P = 0.96, Kolmogorov-Smirnov 2-sample test). MSCV can accurately detect cone photoreceptors on split detection images across a range of eccentricities, enabling quick, objective estimation of photoreceptor mosaic metrics, which will be important for future clinical trials utilizing adaptive optics.

  1. Mammalian-enabled (MENA) protein enhances oncogenic potential and cancer stem cell-like phenotype in hepatocellular carcinoma cells.

    Science.gov (United States)

    Hu, Kunpeng; Huang, Pinzhu; Luo, Hui; Yao, Zhicheng; Wang, Qingliang; Xiong, Zhiyong; Lin, Jizong; Huang, He; Xu, Shilei; Zhang, Peng; Liu, Bo

    2017-08-01

    Mammalian-enabled (MENA) protein is an actin-regulatory protein that influences cell motility and adhesion. It is known to play a role in tumorigenicity of hepatocellular carcinoma (HCC) but the underlying molecular mechanism remains unknown. This study aimed to investigate the oncogenic potential of MENA and its capacity to regulate cancer stem cell (CSC)-like phenotypes in HCC cells. Real-time-PCR and western blot were used to assess mRNA and protein levels of target genes in human HCC tissue specimens and HCC cell lines, respectively. Stable MENA-overexpressing HCC cells were generated from HCC cell lines. Transwell cell migration and colony formation assays were employed to evaluate tumorigenicity. Ectopic expression of MENA significantly enhanced cell migration and colony-forming ability in HCC cells. Overexpression of MENA upregulated several hepatic progenitor/stem cell markers in HCC cells. A high MENA protein level was associated with high mRNA levels of MENA, CD133, cytokeratin 19 (CK19), and epithelial cell adhesion molecule (EpCAM) in human HCC tissues. Overexpression of MENA enhanced epithelial-to-mesenchymal transition (EMT) markers, extracellular signal-regulated kinases (ERK) phosphorylation, and the level of β-catenin in HCC cells. This study demonstrated that overexpression of MENA in HCC cells promoted stem cell markers, EMT markers, and tumorigenicity. These effects may involve, at least partially, the ERK and β-catenin signaling pathways.

  2. Circumvention of regulatory CD4(+) T cell activity during cross-priming strongly enhances T cell-mediated immunity.

    Science.gov (United States)

    Heit, Antje; Gebhardt, Friedemann; Lahl, Katharina; Neuenhahn, Michael; Schmitz, Frank; Anderl, Florian; Wagner, Hermann; Sparwasser, Tim; Busch, Dirk H; Kastenmüller, Kathrin

    2008-06-01

    Immunization with purified antigens is a safe and practical vaccination strategy but is generally unable to induce sustained CD8(+) T cell-mediated protection against intracellular pathogens. Most efforts to improve the CD8(+) T cell immunogenicity of these vaccines have focused on co-administration of adjuvant to support cross-presentation and dendritic cell maturation. In addition, it has been shown that CD4(+) T cell help during the priming phase contributes to the generation of protective CD8(+) memory T cells. In this report we demonstrate that the depletion of CD4(+) T cells paradoxically enhances long-lasting CD8-mediated protective immunity upon protein vaccination. Functional and genetic in vivo inactivation experiments attribute this enhancement primarily to MHC class II-restricted CD4(+) regulatory T cells (Treg), which appear to physiologically suppress the differentiation process towards long-living effector memory T cells. Since, in functional terms, this suppression by Treg largely exceeds the positive effects of conventional CD4(+) T cell help, even the absence of all CD4(+) T cells or lack of MHC class II-mediated interactions on priming dendritic cells result in enhanced CD8(+) T cell immunogenicity. These findings have important implications for the improvement of vaccines against intracellular pathogens or tumors, especially in patients with highly active Treg.

  3. Stimulation of TLR7 with Gardiquimod Enhances Protection and Activation of Immune Cells from γ-Irradiation Exposure

    International Nuclear Information System (INIS)

    Yang, Young-Mi; Bang, Ji-Young; Lee, Suhl-Hyeong; Moon, Tae-Min; Jung, Yu-Jin

    2007-01-01

    Radiotherapy for cancer patients is based on the radiation-induced cell death, but high dose of radiation is able to cause break of immune system. Thus, protection of immune cells from radiation damage is required to enhance the efficiency and reduce the harmful side effects during cancer radiotherapy. Toll-like receptors (TLRs) are important not only in initiating innate immunity against microbial infection, but also inducing Th1-mediated immunity with producing cytokines and chemokines. Cell stimulation via TLRs leads to downstream activation of NF-kB and other transcription factors. Consequently, several genes encoding mediators and effector molecules of the innate as well as the adaptive immune response are transcribed. There are several previous findings that activated immune cells via TLR9 inducing pathways are resistant to chemical or radiation exposure. But it is not clear that the other TLRs also have the same abilities to protect immune cells against cellular damages including γ-irradiation. This research was performed to evaluate protective effect of immune cells from γ-irradiation through TLR-7 activation pathway

  4. Enhancing Solar Cell Efficiency Using Photon Upconversion Materials.

    Science.gov (United States)

    Shang, Yunfei; Hao, Shuwei; Yang, Chunhui; Chen, Guanying

    2015-10-27

    Photovoltaic cells are able to convert sunlight into electricity, providing enough of the most abundant and cleanest energy to cover our energy needs. However, the efficiency of current photovoltaics is significantly impeded by the transmission loss of sub-band-gap photons. Photon upconversion is a promising route to circumvent this problem by converting these transmitted sub-band-gap photons into above-band-gap light, where solar cells typically have high quantum efficiency. Here, we summarize recent progress on varying types of efficient upconversion materials as well as their outstanding uses in a series of solar cells, including silicon solar cells (crystalline and amorphous), gallium arsenide (GaAs) solar cells, dye-sensitized solar cells, and other types of solar cells. The challenge and prospect of upconversion materials for photovoltaic applications are also discussed.

  5. Enhancing Solar Cell Efficiency Using Photon Upconversion Materials

    Directory of Open Access Journals (Sweden)

    Yunfei Shang

    2015-10-01

    Full Text Available Photovoltaic cells are able to convert sunlight into electricity, providing enough of the most abundant and cleanest energy to cover our energy needs. However, the efficiency of current photovoltaics is significantly impeded by the transmission loss of sub-band-gap photons. Photon upconversion is a promising route to circumvent this problem by converting these transmitted sub-band-gap photons into above-band-gap light, where solar cells typically have high quantum efficiency. Here, we summarize recent progress on varying types of efficient upconversion materials as well as their outstanding uses in a series of solar cells, including silicon solar cells (crystalline and amorphous, gallium arsenide (GaAs solar cells, dye-sensitized solar cells, and other types of solar cells. The challenge and prospect of upconversion materials for photovoltaic applications are also discussed

  6. A T-cell specific transcriptional enhancer element 3' of Cα in the human T-cell receptor α locus

    International Nuclear Information System (INIS)

    Ho, Icheng; Yang, Lihsuan; Morle, G.; Leiden, J.M.

    1989-01-01

    A transcriptional enhancer element has been identified 4.5 kilobases 3' of C α (constant region α chain) in the human T-cell receptor (TCR) α-chain locus. This enhancer is active on both a TCR V α (variable region α chain) promoter and the minimal simian virus 40 promoter in TCR α/β Jurkat and EL4 cells but is inactive on a V α promoter TCR γ/δ PEER and Molt-13 cells, clone 13 B cells, and HeLa fibroblasts. The enhancer has been localized to a 116-base-pair BstXI/Dra I restriction enzyme fragment, which lacks immunoglobulin octamer and κB enhancer motifs but does contain a consensus cAMP-response element (CRE). DNase I footprint analyses demonstrated that the minimal enhancer contains two binding sites for Jurkat nuclear proteins. One of these sites corresponds to the CRE, while the other does not correspond to a known transcriptional enhancer motif. These data support a model in which TCR α gene transcription is regulated by a unique set of cis-acting sequences and trans-acting factors, which are differentially active in cells of the TCR α/β lineage. In addition, the TCR α enhancer may play a role in activating oncogene expression in T-lymphoblastoid tumors that have previously been shown to display chromosomal translocations into the human TCR α locus

  7. Human mesenchymal stromal cells enhance the immunomodulatory function of CD8+CD28− regulatory T cells

    Science.gov (United States)

    Liu, Qiuli; Zheng, Haiqing; Chen, Xiaoyong; Peng, Yanwen; Huang, Weijun; Li, Xiaobo; Li, Gang; Xia, Wenjie; Sun, Qiquan; Xiang, Andy Peng

    2015-01-01

    One important aspect of mesenchymal stromal cells (MSCs)-mediated immunomodulation is the recruitment and induction of regulatory T (Treg) cells. However, we do not yet know whether MSCs have similar effects on the other