Efficient Transduction of Human and Rhesus Macaque Primary T Cells by a Modified Human Immunodeficiency Virus Type 1–Based Lentiviral Vector

PubMed Central

He, Huan; Xue, Jing; Wang, Weiming; Liu, Lihong; Ye, Chaobaihui; Cong, Zhe; Kimata, Jason T.; Qin, Chuan; Zhou, Paul

2017-01-01

Human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors efficiently transduce genes to human, but not rhesus, primary T cells and hematopoietic stem cells (HSCs). The poor transduction of HIV-1 vectors to rhesus cells is mainly due to species-specific restriction factors such as rhesus TRIM5α. Previously, several strategies to modify HIV-1 vectors were developed to overcome rhesus TRIM5α restriction. While the modified HIV-1 vectors efficiently transduce rhesus HSCs, they remain suboptimal for rhesus primary T cells. Recently, HIV-1 variants that encode combinations of LNEIE mutations in capsid (CA) protein and SIVmac239 Vif were found to replicate efficiently in rhesus primary T cells. Thus, the present study tested whether HIV-1 vectors packaged by a packaging construct containing these CA substitutions could efficiently transduce both human and rhesus primary CD4 T cells. To accomplish this, LNEIE mutations were made in the packaging construct CEMΔ8.9, and recombinant HIV-1 vectors packaged by Δ8.9 WT or Δ8.9 LNEIE were generated. Transduction rates, CA stability, and vector integration in CEMss-CCR5 and CEMss-CCR5-rhTRIM5α/green fluorescent protein cells, as well as transduction rates in human and rhesus primary CD4 T cells by Δ8.9 WT or Δ8.9 LNEIE-packaged HIV-1 vectors, were compared. Finally, the influence of rhesus TRIM5α variations in transduction rates to primary CD4 T cells from a cohort of 37 Chinese rhesus macaques was studied. While it maintains efficient transduction for human T-cell line and primary CD4 T cells, Δ8.9 LNEIE-packaged HIV-1 vector overcomes rhesus TRIM5α-mediated CA degradation, resulting in significantly higher transduction efficiency of rhesus primary CD4 T cells than Δ8.9 WT-packaged HIV-1 vector. Rhesus TRIM5α variations strongly influence transduction efficiency of rhesus primary CD4 T cells by both Δ8.9 WT or Δ8.9 LNEIE-packaged HIV-1 vectors. Thus, it is concluded that Δ8.9 LNEIE-packaged HIV-1

Intravenous administration of the adeno-associated virus-PHP.B capsid fails to upregulate transduction efficiency in the marmoset brain.

PubMed

Matsuzaki, Yasunori; Konno, Ayumu; Mochizuki, Ryuta; Shinohara, Yoichiro; Nitta, Keisuke; Okada, Yukihiro; Hirai, Hirokazu

2018-02-05

Intravenous administration of adeno-associated virus (AAV)-PHP.B, a capsid variant of AAV9 containing seven amino acid insertions, results in a greater permeability of the blood brain barrier (BBB) than standard AAV9 in mice, leading to highly efficient and global transduction of the central nervous system (CNS). The present study aimed to examine whether the enhanced BBB penetrance of AAV-PHP.B observed in mice also occurs in non-human primates. Thus, a young adult (age, 1.6 years) and an old adult (age, 7.2 years) marmoset received an intravenous injection of AAV-PHP.B expressing enhanced green fluorescent protein (EGFP) under the control of the constitutive CBh promoter (a hybrid of cytomegalovirus early enhancer and chicken β-actin promoter). Age-matched control marmosets were treated with standard AAV9-capsid vectors. The animals were sacrificed 6 weeks after the viral injection. Based on the results, only limited transduction of neurons (0-2%) and astrocytes (0.1-2.5%) was observed in both AAV-PHP.B- and AAV9-treated marmosets. One noticeable difference between AAV-PHP.B and AAV9 was the marked transduction of the peripheral dorsal root ganglia neurons. Indeed, the soma and axons in the projection from the spinal cord to the nucleus cuneatus in the medulla oblongata were strongly labeled with EGFP by AAV-PHP.B. Thus, except for the peripheral dorsal root ganglia neurons, the AAV-PHP.B transduction efficiency in the CNS of marmosets was comparable to that of AAV9 vectors. Copyright © 2017 Elsevier B.V. All rights reserved.

Adeno-Associated Virus Type 6 (AAV6) Vectors Mediate Efficient Transduction of Airway Epithelial Cells in Mouse Lungs Compared to That of AAV2 Vectors

PubMed Central

Halbert, Christine L.; Allen, James M.; Miller, A. Dusty

2001-01-01

Although vectors derived from adeno-associated virus type 2 (AAV2) promote gene transfer and expression in many somatic tissues, studies with animal models and cultured cells show that the apical surface of airway epithelia is resistant to transduction by AAV2 vectors. Approaches to increase transduction rates include increasing the amount of vector and perturbing the integrity of the epithelia. In this study, we explored the use of vectors based on AAV6 to increase transduction rates in airways. AAV vectors were made using combinations of rep, cap, and packaged genomes from AAV2 or AAV6. The packaged genomes encoded human placental alkaline phosphatase and contained terminal repeat sequences from AAV2 or AAV6. We found that transduction efficiency was primarily dependent on the source of Cap protein, defined here as the vector pseudotype. The AAV6 and AAV2 pseudotype vectors exhibited different tropisms in tissue-cultured cells, and cell transduction by AAV6 vectors was not inhibited by heparin, nor did they compete for entry in a transduction assay, indicating that AAV6 and AAV2 capsid bind different receptors. In vivo analysis of vectors showed that AAV2 pseudotype vectors gave high transduction rates in alveolar cells but much lower rates in the airway epithelium. In contrast, the AAV6 pseudotype vectors exhibited much more efficient transduction of epithelial cells in large and small airways, showing up to 80% transduction in some airways. These results, combined with our previous results showing lower immunogenicity of AAV6 than of AAV2 vectors, indicate that AAV6 vectors may provide significant advantages over AAV2 for gene therapy of lung diseases like cystic fibrosis. PMID:11413329

Heavy metal accumulation and signal transduction in herbaceous and woody plants: Paving the way for enhancing phytoremediation efficiency.

PubMed

Luo, Zhi-Bin; He, Jiali; Polle, Andrea; Rennenberg, Heinz

2016-11-01

Heavy metal (HM)-accumulating herbaceous and woody plants are employed for phytoremediation. To develop improved strategies for enhancing phytoremediation efficiency, knowledge of the microstructural, physiological and molecular responses underlying HM-accumulation is required. Here we review the progress in understanding the structural, physiological and molecular mechanisms underlying HM uptake, transport, sequestration and detoxification, as well as the regulation of these processes by signal transduction in response to HM exposure. The significance of genetic engineering for enhancing phytoremediation efficiency is also discussed. In herbaceous plants, HMs are taken up by roots and transported into the root cells via transmembrane carriers for nutritional ions. The HMs absorbed by root cells can be further translocated to the xylem vessels and unloaded into the xylem sap, thereby reaching the aerial parts of plants. HMs can be sequestered in the cell walls, vacuoles and the Golgi apparatuses. Plant roots initially perceive HM stress and trigger the signal transduction, thereby mediating changes at the molecular, physiological, and microstructural level. Signaling molecules such as phytohormones, reactive oxygen species (ROS) and nitric oxide (NO), modulate plant responses to HMs via differentially expressed genes, activation of the antioxidative system and coordinated cross talk among different signaling molecules. A number of genes participated in HM uptake, transport, sequestration and detoxification have been functionally characterized and transformed to target plants for enhancing phytoremediation efficiency. Fast growing woody plants hold an advantage over herbaceous plants for phytoremediation in terms of accumulation of high HM-amounts in their large biomass. Presumably, woody plants accumulate HMs using similar mechanisms as herbaceous counterparts, but the processes of HM accumulation and signal transduction can be more complex in woody plants

Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

PubMed

Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

2017-09-01

Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sung, Min Sun; Biosystems and Bioengineering Program, University of Science and Technology; Mun, Ji-Young

2013-07-19

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

Surmounting limited gene delivery into primary immune cell populations: Efficient cell type-specific adenoviral transduction by CAR.

PubMed

Clausen, Björn E; Brand, Anna; Karram, Khalad

2015-06-01

Ectopic gene expression studies in primary immune cells have been notoriously difficult to perform due to the limitations in conventional transfection and viral transduction methods. Although replication-defective adenoviruses provide an attractive alternative for gene delivery, their use has been hampered by the limited susceptibility of murine leukocytes to adenoviral infection, due to insufficient expression of the human coxsackie/adenovirus receptor (CAR). In this issue of the European Journal of Immunology, Heger et al. [Eur. J. Immunol. 2015. 45: XXXX-XXXX] report the generation of transgenic mice that enable conditional Cre/loxP-mediated expression of human CAR. The authors demonstrate that this R26/CAG-CAR∆1(StopF) mouse strain facilitates the faithful monitoring of Cre activity in situ as well as the specific and efficient adenoviral transduction of primary immune cell populations in vitro. Further tweaking of the system towards more efficient gene transfer in vivo remains a future challenge. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Expression levels of the PiT-2 receptor explain, in part, the gestational age-dependent alterations in transduction efficiency after in utero retroviral-mediated gene transfer

PubMed Central

Ozturk, Ferhat; Park, Paul J.; Tellez, Joseph; Colletti, Evan; Eiden, Maribeth V.; Almeida-Porada, Graça; Porada, Christopher D.

2014-01-01

Background A fundamental obstacle to using retroviral-mediated gene transfer (GT) to treat human diseases is the relatively low transduction levels that have been achieved in clinically relevant human cells. We previously showed that performing GT in utero overcomes this obstacle and results in significant levels of transduction within multiple fetal organs, with different tissues exhibiting optimal transduction at different developmental stages. We undertook the present study aiming to elucidate the mechanism for this age-dependent transduction, testing the two factors that we hypothesized could be responsible: (i) the proliferative status of the tissue at the time of GT and (ii) the expression level of the amphotropic PiT-2 receptor. Methods Immunofluorescence was performed on tissues from sheep of varying developmental stages to assess the proliferative status of the predominant cells within each organ as a function of age. After developing an enzyme-linked immunosorbent assay (ELISA) and a quantitative reverse transcription chain reaction (qRT-PCR) assay, we then quantified PiT-2 expression at the protein and mRNA levels, respectively. Results The results obtained indicate that the proliferative status of organs at the time of fetal GT is not the major determinant governing transduction efficiency. By contrast, our ELISA and qRT-PCR analyses demonstrated that PiT-2 mRNA and protein levels vary with gestational age, correlating with the observed differences in transduction efficiency. Conclusions The findings of the present study explain the age-related differences that we previously observed in transduction efficiency after in utero GT. They also suggest it may be possible to achieve relatively selective GT to specific tissues by performing in utero GT when levels of PiT-2 are maximal in the desired target organ. PMID:22262359

Highly efficient gene transfer using a retroviral vector into murine T cells for preclinical chimeric antigen receptor-expressing T cell therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kusabuka, Hotaka; Fujiwara, Kento; Tokunaga, Yusuke

Adoptive immunotherapy using chimeric antigen receptor-expressing T (CAR-T) cells has attracted attention as an efficacious strategy for cancer treatment. To prove the efficacy and safety of CAR-T cell therapy, the elucidation of immunological mechanisms underlying it in mice is required. Although a retroviral vector (Rv) is mainly used for the introduction of CAR to murine T cells, gene transduction efficiency is generally less than 50%. The low transduction efficiency causes poor precision in the functional analysis of CAR-T cells. We attempted to improve the Rv gene transduction protocol to more efficiently generate functional CAR-T cells by optimizing the period ofmore » pre-cultivation and antibody stimulation. In the improved protocol, gene transduction efficiency to murine T cells was more than 90%. In addition, almost all of the prepared murine T cells expressed CAR after puromycin selection. These CAR-T cells had antigen-specific cytotoxic activity and secreted multiple cytokines by antigen stimulation. We believe that our optimized gene transduction protocol for murine T cells contributes to the advancement of T cell biology and development of immunotherapy using genetically engineered T cells. - Highlights: • We established highly efficient gene transduction protocols for murine T cells. • CD8{sup +} CAR-T cells had antigen-specific cytotoxic activity. • CD4{sup +} CAR-T cells secreted multiple cytokines by antigen stimulation. • This finding can contribute to the development of T-cell biology and immunotherapy.« less

Magnetic nanoparticles enhance adenovirus transduction in vitro and in vivo.

PubMed

Sapet, Cédric; Pellegrino, Christophe; Laurent, Nicolas; Sicard, Flavie; Zelphati, Olivier

2012-05-01

Adenoviruses are among the most powerful gene delivery systems. Even if they present low potential for oncogenesis, there is still a need for minimizing widespread delivery to avoid deleterious reactions. In this study, we investigated Magnetofection efficiency to concentrate and guide vectors for an improved targeted delivery. Magnetic nanoparticles formulations were complexed to a replication defective Adenovirus and were used to transduce cells both in vitro and in vivo. A new integrated magnetic procedure for cell sorting and genetic modification (i-MICST) was also investigated. Magnetic nanoparticles enhanced viral transduction efficiency and protein expression in a dose-dependent manner. They accelerated the transduction kinetics and allowed non-permissive cells infection. Magnetofection greatly improved adenovirus-mediated DNA delivery in vivo and provided a magnetic targeting. The i-MICST results established the efficiency of magnetic nanoparticles assisted viral transduction within cell sorting columns. The results showed that the combination of Magnetofection and Adenoviruses represents a promising strategy for gene therapy. Recently, a new integrated method to combine clinically approved magnetic cell isolation devices and genetic modification was developed. In this study, we validated that magnetic cell separation and adenoviral transduction can be accomplished in one reliable integrated and safe system.

Top-Down CMOS-NEMS Polysilicon Nanowire with Piezoresistive Transduction

PubMed Central

Marigó, Eloi; Sansa, Marc; Pérez-Murano, Francesc; Uranga, Arantxa; Barniol, Núria

2015-01-01

A top-down clamped-clamped beam integrated in a CMOS technology with a cross section of 500 nm × 280 nm has been electrostatic actuated and sensed using two different transduction methods: capacitive and piezoresistive. The resonator made from a single polysilicon layer has a fundamental in-plane resonance at 27 MHz. Piezoresistive transduction avoids the effect of the parasitic capacitance assessing the capability to use it and enhance the CMOS-NEMS resonators towards more efficient oscillator. The displacement derived from the capacitive transduction allows to compute the gauge factor for the polysilicon material available in the CMOS technology. PMID:26184222

Top-Down CMOS-NEMS Polysilicon Nanowire with Piezoresistive Transduction.

PubMed

Marigó, Eloi; Sansa, Marc; Pérez-Murano, Francesc; Uranga, Arantxa; Barniol, Núria

2015-07-14

A top-down clamped-clamped beam integrated in a CMOS technology with a cross section of 500 nm × 280 nm has been electrostatic actuated and sensed using two different transduction methods: capacitive and piezoresistive. The resonator made from a single polysilicon layer has a fundamental in-plane resonance at 27 MHz. Piezoresistive transduction avoids the effect of the parasitic capacitance assessing the capability to use it and enhance the CMOS-NEMS resonators towards more efficient oscillator. The displacement derived from the capacitive transduction allows to compute the gauge factor for the polysilicon material available in the CMOS technology.

Mechanical transduction via a single soft polymer

NASA Astrophysics Data System (ADS)

Hou, Ruizheng; Wang, Nan; Bao, Weizhu; Wang, Zhisong

2018-04-01

Molecular machines from biology and nanotechnology often depend on soft structures to perform mechanical functions, but the underlying mechanisms and advantages or disadvantages over rigid structures are not fully understood. We report here a rigorous study of mechanical transduction along a single soft polymer based on exact solutions to the realistic three-dimensional wormlike-chain model and augmented with analytical relations derived from simpler polymer models. The results reveal surprisingly that a soft polymer with vanishingly small persistence length below a single chemical bond still transduces biased displacement and mechanical work up to practically significant amounts. This "soft" approach possesses unique advantages over the conventional wisdom of rigidity-based transduction, and potentially leads to a unified mechanism for effective allosterylike transduction and relay of mechanical actions, information, control, and molecules from one position to another in molecular devices and motors. This study also identifies an entropy limit unique to the soft transduction, and thereby suggests a possibility of detecting higher efficiency for kinesin motor and mutants in future experiments.

Pantropic retroviruses as a transduction tool for sea urchin embryos

PubMed Central

Core, Amanda B.; Reyna, Arlene E.; Conaway, Evan A.; Bradham, Cynthia A.

2012-01-01

Sea urchins are an important model for experiments at the intersection of development and systems biology, and technical innovations that enhance the utility of this model are of great value. This study explores pantropic retroviruses as a transduction tool for sea urchin embryos, and demonstrates that pantropic retroviruses infect sea urchin embryos with high efficiency and genomically integrate at a copy number of one per cell. We successfully used a self-inactivation strategy to both insert a sea urchin-specific enhancer and disrupt the endogenous viral enhancer. The resulting self-inactivating viruses drive global and persistent gene expression, consistent with genomic integration during the first cell cycle. Together, these data provide substantial proof of principle for transduction technology in sea urchin embryos. PMID:22431628

Characterization of retroviral infectivity and superinfection resistance during retrovirus-mediated transduction of mammalian cells.

PubMed

Liao, J; Wei, Q; Fan, J; Zou, Y; Song, D; Liu, J; Liu, F; Ma, C; Hu, X; Li, L; Yu, Y; Qu, X; Chen, L; Yu, X; Zhang, Z; Zhao, C; Zeng, Z; Zhang, R; Yan, S; Wu, T; Wu, X; Shu, Y; Lei, J; Li, Y; Zhang, W; Wang, J; Reid, R R; Lee, M J; Huang, W; Wolf, J M; He, T-C; Wang, J

2017-06-01

Retroviral vectors including lentiviral vectors are commonly used tools to stably express transgenes or RNA molecules in mammalian cells. Their utilities are roughly divided into two categories, stable overexpression of transgenes and RNA molecules, which requires maximal transduction efficiency, or functional selection with retrovirus (RV)-based libraries, which takes advantage of retroviral superinfection resistance. However, the dynamic features of RV-mediated transduction are not well characterized. Here, we engineered two murine stem cell virus-based retroviral vectors expressing dual fluorescence proteins and antibiotic markers, and analyzed virion production efficiency and virion stability, dynamic infectivity and superinfection resistance in different cell types, and strategies to improve transduction efficiency. We found that the highest virion production occurred between 60 and 72 h after transfection. The stability of the collected virion supernatant decreased by >60% after 3 days in storage. We found that RV infectivity varied drastically in the tested human cancer lines, while low transduction efficiency was partially overcome with increased virus titer, prolonged infection duration and/or repeated infections. Furthermore, we demonstrated that RV receptors PIT1 and PIT2 were lowly expressed in the analyzed cells, and that PIT1 and/or PIT2 overexpression significantly improved transduction efficiency in certain cell lines. Thus, our findings provide resourceful information for the optimal conditions of retroviral-mediated gene delivery.

Meeting Report: Teaching Signal Transduction

PubMed Central

Kramer, IJsbrand; Thomas, Geraint

2006-01-01

In July, 2005, the European Institute of Chemistry and Biology at the campus of the University of Bordeaux, France, hosted a focused week of seminars, workshops, and discussions around the theme of “teaching signal transduction.” The purpose of the summer school was to offer both junior and senior university instructors a chance to reflect on the development and delivery of their teaching activities in this area. This was achieved by combining open seminars with restricted access workshops and discussion events. The results suggest ways in which systems biology, information and communication technology, Web-based investigations, and high standard illustrations might be more effectively and efficiently incorporated into modern cell biology courses. PMID:17012185

Chemical Modification with High Molecular Weight Polyethylene Glycol Reduces Transduction of Hepatocytes and Increases Efficacy of Intravenously Delivered Oncolytic Adenovirus

PubMed Central

Doronin, Konstantin; Shashkova, Elena V.; May, Shannon M.; Hofherr, Sean E.

2009-01-01

Abstract Oncolytic adenoviruses are anticancer agents that replicate within tumors and spread to uninfected tumor cells, amplifying the anticancer effect of initial transduction. We tested whether coating the viral particle with polyethylene glycol (PEG) could reduce transduction of hepatocytes and hepatotoxicity after systemic (intravenous) administration of oncolytic adenovirus serotype 5 (Ad5). Conjugating Ad5 with high molecular weight 20-kDa PEG but not with 5-kDa PEG reduced hepatocyte transduction and hepatotoxicity after intravenous injection. PEGylation with 20-kDa PEG was as efficient at detargeting adenovirus from Kupffer cells and hepatocytes as virus predosing and warfarin. Bioluminescence imaging of virus distribution in two xenograft tumor models in nude mice demonstrated that PEGylation with 20-kDa PEG reduced liver infection 19- to 90-fold. Tumor transduction levels were similar for vectors PEGylated with 20-kDa PEG and unPEGylated vectors. Anticancer efficacy after a single intravenous injection was retained at the level of unmodified vector in large established prostate carcinoma xenografts, resulting in complete elimination of tumors in all animals and long-term tumor-free survival. Anticancer efficacy after a single intravenous injection was increased in large established hepatocellular carcinoma xenografts, resulting in significant prolongation of survival as compared with unmodified vector. The increase in efficacy was comparable to that obtained with predosing and warfarin pretreatment, significantly extending the median of survival. Shielding adenovirus with 20-kDa PEG may be a useful approach to improve the therapeutic window of oncolytic adenovirus after systemic delivery to primary and metastatic tumor sites. PMID:19469693

Superior In vivo Transduction of Human Hepatocytes Using Engineered AAV3 Capsid.

PubMed

Vercauteren, Koen; Hoffman, Brad E; Zolotukhin, Irene; Keeler, Geoffrey D; Xiao, Jing W; Basner-Tschakarjan, Etiena; High, Katherine A; Ertl, Hildegund Cj; Rice, Charles M; Srivastava, Arun; de Jong, Ype P; Herzog, Roland W

2016-06-01

Adeno-associated viral (AAV) vectors are currently being tested in multiple clinical trials for liver-directed gene transfer to treat the bleeding disorders hemophilia A and B and metabolic disorders. The optimal viral capsid for transduction of human hepatocytes has been under active investigation, but results across various models are inconsistent. We tested in vivo transduction in "humanized" mice. Methods to quantitate percent AAV transduced human and murine hepatocytes in chimeric livers were optimized using flow cytometry and confocal microscopy with image analysis. Distinct transduction efficiencies were noted following peripheral vein administration of a self-complementary vector expressing a gfp reporter gene. An engineered AAV3 capsid with two amino acid changes, S663V+T492V (AAV3-ST), showed best efficiency for human hepatocytes (~3-times, ~8-times, and ~80-times higher than for AAV9, AAV8, and AAV5, respectively). AAV5, 8, and 9 were more efficient in transducing murine than human hepatocytes. AAV8 yielded the highest transduction rate of murine hepatocytes, which was 19-times higher than that for human hepatocytes. In summary, our data show substantial differences among AAV serotypes in transduction of human and mouse hepatocytes, are the first to report on AAV5 in humanized mice, and support the use of AAV3-based vectors for human liver gene transfer.

Experimental demonstration of high fidelity entanglement distribution over decoherence channels via qubit transduction

PubMed Central

Lim, Hyang-Tag; Hong, Kang-Hee; Kim, Yoon-Ho

2015-01-01

Quantum coherence and entanglement, which are essential resources for quantum information, are often degraded and lost due to decoherence. Here, we report a proof-of-principle experimental demonstration of high fidelity entanglement distribution over decoherence channels via qubit transduction. By unitarily switching the initial qubit encoding to another, which is insensitive to particular forms of decoherence, we have demonstrated that it is possible to avoid the effect of decoherence completely. In particular, we demonstrate high-fidelity distribution of photonic polarization entanglement over quantum channels with two types of decoherence, amplitude damping and polarization-mode dispersion, via qubit transduction between polarization qubits and dual-rail qubits. These results represent a significant breakthrough in quantum communication over decoherence channels as the protocol is input-state independent, requires no ancillary photons and symmetries, and has near-unity success probability. PMID:26487083

Experimental demonstration of high fidelity entanglement distribution over decoherence channels via qubit transduction.

PubMed

Lim, Hyang-Tag; Hong, Kang-Hee; Kim, Yoon-Ho

2015-10-21

Quantum coherence and entanglement, which are essential resources for quantum information, are often degraded and lost due to decoherence. Here, we report a proof-of-principle experimental demonstration of high fidelity entanglement distribution over decoherence channels via qubit transduction. By unitarily switching the initial qubit encoding to another, which is insensitive to particular forms of decoherence, we have demonstrated that it is possible to avoid the effect of decoherence completely. In particular, we demonstrate high-fidelity distribution of photonic polarization entanglement over quantum channels with two types of decoherence, amplitude damping and polarization-mode dispersion, via qubit transduction between polarization qubits and dual-rail qubits. These results represent a significant breakthrough in quantum communication over decoherence channels as the protocol is input-state independent, requires no ancillary photons and symmetries, and has near-unity success probability.

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

PubMed

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

2018-06-15

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

Efficient Generation of Functional Hepatocytes From Human Embryonic Stem Cells and Induced Pluripotent Stem Cells by HNF4α Transduction

PubMed Central

Takayama, Kazuo; Inamura, Mitsuru; Kawabata, Kenji; Katayama, Kazufumi; Higuchi, Maiko; Tashiro, Katsuhisa; Nonaka, Aki; Sakurai, Fuminori; Hayakawa, Takao; Kusuda Furue, Miho; Mizuguchi, Hiroyuki

2012-01-01

Hepatocyte-like cells from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are expected to be a useful source of cells drug discovery. Although we recently reported that hepatic commitment is promoted by transduction of SOX17 and HEX into human ESC- and iPSC-derived cells, these hepatocyte-like cells were not sufficiently mature for drug screening. To promote hepatic maturation, we utilized transduction of the hepatocyte nuclear factor 4α (HNF4α) gene, which is known as a master regulator of liver-specific gene expression. Adenovirus vector-mediated overexpression of HNF4α in hepatoblasts induced by SOX17 and HEX transduction led to upregulation of epithelial and mature hepatic markers such as cytochrome P450 (CYP) enzymes, and promoted hepatic maturation by activating the mesenchymal-to-epithelial transition (MET). Thus HNF4α might play an important role in the hepatic differentiation from human ESC-derived hepatoblasts by activating the MET. Furthermore, the hepatocyte like-cells could catalyze the toxication of several compounds. Our method would be a valuable tool for the efficient generation of functional hepatocytes derived from human ESCs and iPSCs, and the hepatocyte-like cells could be used for predicting drug toxicity. PMID:22068426

Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction

PubMed Central

Mano, Miguel; Ippodrino, Rudy; Zentilin, Lorena; Zacchigna, Serena; Giacca, Mauro

2015-01-01

Viral vectors based on the adeno-associated virus (AAV) hold great promise for in vivo gene transfer; several unknowns, however, still limit the vectors’ broader and more efficient application. Here, we report the results of a high-throughput, whole-genome siRNA screening aimed at identifying cellular factors regulating AAV transduction. We identified 1,483 genes affecting vector efficiency more than 4-fold and up to 50-fold, either negatively or positively. Most of these factors have not previously been associated to AAV infection. The most effective siRNAs were independent from the virus serotype or analyzed cell type and were equally evident for single-stranded and self-complementary AAV vectors. A common characteristic of the most effective siRNAs was the induction of cellular DNA damage and activation of a cell cycle checkpoint. This information can be exploited for the development of more efficient AAV-based gene delivery procedures. Administration of the most effective siRNAs identified by the screening to the liver significantly improved in vivo AAV transduction efficiency. PMID:26305933

A survey of ex vivo/in vitro transduction efficiency of mammalian primary cells and cell lines with Nine natural adeno-associated virus (AAV1-9) and one engineered adeno-associated virus serotype.

PubMed

Ellis, Brian L; Hirsch, Matthew L; Barker, Jenny C; Connelly, Jon P; Steininger, Robert J; Porteus, Matthew H

2013-03-06

The ability to deliver a gene of interest into a specific cell type is an essential aspect of biomedical research. Viruses can be a useful tool for this delivery, particularly in difficult to transfect cell types. Adeno-associated virus (AAV) is a useful gene transfer vector because of its ability to mediate efficient gene transduction in numerous dividing and quiescent cell types, without inducing any known pathogenicity. There are now a number of natural for that designed AAV serotypes that each has a differential ability to infect a variety of cell types. Although transduction studies have been completed, the bulk of the studies have been done in vivo, and there has never been a comprehensive study of transduction ex vivo/in vitro. Each cell type was infected with each serotype at a multiplicity of infection of 100,000 viral genomes/cell and transduction was analyzed by flow cytometry + . We found that AAV1 and AAV6 have the greatest ability to transduce a wide range of cell types, however, for particular cell types, there are specific serotypes that provide optimal transduction. In this work, we describe the transduction efficiency of ten different AAV serotypes in thirty-four different mammalian cell lines and primary cell types. Although these results may not be universal due to numerous factors such as, culture conditions and/ or cell growth rates and cell heterogeneity, these results provide an important and unique resource for investigators who use AAV as an ex vivo gene delivery vector or who work with cells that are difficult to transfect.

Integration of adeno-associated virus vectors in CD34+ human hematopoietic progenitor cells after transduction.

PubMed

Fisher-Adams, G; Wong, K K; Podsakoff, G; Forman, S J; Chatterjee, S

1996-07-15

Gene transfer vectors based on adeno-associated virus (AAV) appear promising because of their high transduction frequencies regardless of cell cycle status and ability to integrate into chromosomal DNA. We tested AAV-mediated gene transfer into a panel of human bone marrow or umbilical cord-derived CD34+ hematopoietic progenitor cells, using vectors encoding several transgenes under the control of viral and cellular promoters. Gene transfer was evaluated by (1) chromosomal integration of vector sequences and (2) analysis of transgene expression. Southern hybridization and fluorescence in situ hybridization analysis of transduced CD34 genomic DNA showed the presence of integrated vector sequences in chromosomal DNA in a portion of transduced cells and showed that integrated vector sequences were replicated along with cellular DNA during mitosis. Transgene expression in transduced CD34 cells in suspension cultures and in myeloid colonies differentiating in vitro from transduced CD34 cells approximated that predicted by the multiplicity of transduction. This was true in CD34 cells from different donors, regardless of the transgene or selective pressure. Comparisons of CD34 cell transduction either before or after cytokine stimulation showed similar gene transfer frequencies. Our findings suggest that AAV transduction of CD34+ hematopoietic progenitor cells is efficient, can lead to stable integration in a population of transduced cells, and may therefore provide the basis for safe and efficient ex vivo gene therapy of the hematopoietic system.

Phenomenally High Transduction Air/gas Transducers for Practical Non-Contact Ultrasonic Applications

NASA Astrophysics Data System (ADS)

Bhardwaj, Mahesh C.

2009-03-01

Based on novel acoustic impedance matching layers and high coupling piezoelectric materials this paper describes exceptionally high air/gas transduction ultrasonic transducers. By providing applications oriented performance of these transducers we also usher in the era of much desired Non-Contact Ultrasound (NCU) testing and analysis of a wide range of materials including early stage formation of materials such as uncured composite prepregs, green ceramics and powder metals, plastics, elastomers, porous, hygroscopic, chemically bonded and other materials. Besides quality control, ultimately NCU offers timely opportunities for cost-effective materials production, energy savings, and environment protection.

Enhanced Central Nervous System Transduction with Lentiviral Vectors Pseudotyped with RVG/HIV-1gp41 Chimeric Envelope Glycoproteins

PubMed Central

Trabalza, Antonio; Eleftheriadou, Ioanna; Sgourou, Argyro; Liao, Ting-Yi; Patsali, Petros; Lee, Heyne

2014-01-01

ABSTRACT To investigate the potential benefits which may arise from pseudotyping the HIV-1 lentiviral vector with its homologous gp41 envelope glycoprotein (GP) cytoplasmic tail (CT), we created chimeric RVG/HIV-1gp41 GPs composed of the extracellular and transmembrane sequences of RVG and either the full-length gp41 CT or C terminus gp41 truncations sequentially removing existing conserved motifs. Lentiviruses (LVs) pseudotyped with the chimeric GPs were evaluated in terms of particle release (physical titer), biological titers, infectivity, and in vivo central nervous system (CNS) transduction. We report here that LVs carrying shorter CTs expressed higher levels of envelope GP and showed a higher average infectivity than those bearing full-length GPs. Interestingly, complete removal of GP CT led to vectors with the highest transduction efficiency. Removal of all C-terminal gp41 CT conserved motifs, leaving just 17 amino acids (aa), appeared to preserve infectivity and resulted in a significantly increased physical titer. Furthermore, incorporation of these 17 aa in the RVG CT notably enhanced the physical titer. In vivo stereotaxic delivery of LV vectors exhibiting the best in vitro titers into rodent striatum facilitated efficient transduction of the CNS at the site of injection. A particular observation was the improved retrograde transduction of neurons in connected distal sites that resulted from the chimeric envelope R5 which included the “Kennedy” sequence (Ken) and lentivirus lytic peptide 2 (LLP2) conserved motifs in the CT, and although it did not exhibit a comparable high titer upon pseudotyping, it led to a significant increase in distal retrograde transduction of neurons. IMPORTANCE In this study, we have produced novel chimeric envelopes bearing the extracellular domain of rabies fused to the cytoplasmic tail (CT) of gp41 and pseudotyped lentiviral vectors with them. Here we report novel effects on the transduction efficiency and physical titer

A parallel algorithm for multi-level logic synthesis using the transduction method. M.S. Thesis

NASA Technical Reports Server (NTRS)

Lim, Chieng-Fai

1991-01-01

The Transduction Method has been shown to be a powerful tool in the optimization of multilevel networks. Many tools such as the SYLON synthesis system (X90), (CM89), (LM90) have been developed based on this method. A parallel implementation is presented of SYLON-XTRANS (XM89) on an eight processor Encore Multimax shared memory multiprocessor. It minimizes multilevel networks consisting of simple gates through parallel pruning, gate substitution, gate merging, generalized gate substitution, and gate input reduction. This implementation, called Parallel TRANSduction (PTRANS), also uses partitioning to break large circuits up and performs inter- and intra-partition dynamic load balancing. With this, good speedups and high processor efficiencies are achievable without sacrificing the resulting circuit quality.

The third helix of the murine Hoxc8 homeodomain facilitates protein transduction in mammalian cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kong, Kyoung-Ah; Gadi, Jogeswar; Park, Hyoung Woo

2008-12-05

Previously, we have demonstrated that purified Hoxc8 homeoprotein has the ability to penetrate the cellular membrane and can be transduced efficiently into COS-7 cells. Moreover, the Hoxc8 protein is able to form a complex with DNA molecules in vitro and helps the DNA be delivered intracellularly, serving as a gene delivery vehicle. Here, we further analyzed the membrane transduction activity of Hoxc8 protein and provide the evidence that the 16 amino acid (a.a.191-206, 2.23 kDa) third helix of murine Hoxc8 protein is an efficient protein transduction domain (PTD). When the 16 amino acid peptide was fused at the carboxyl terminalmore » of enhanced green fluorescence protein (EGFP), the fusion proteins were transduced efficiently into the primary pig fetal fibroblast cells. The transduction efficiency increased in a concentration-dependent manner up to 1 {mu}M, and appeared to plateau above a concentration of 1 {mu}M. When tandem multimers of PTD, EGFP-PTD(2), EGFP-PTD(3), EGFP-PTD(4), and EGFP-PTD(5), were analyzed at 500 nM of concentration, the penetrating efficiency increased in a dose-dependent manner. As the number of PTDs increased, the EGFP signal also increased, although the signal maintained plateau after EGFP-PTD(3). These results indicate that the 16 amino acid third helix is the key element responsible for the membrane transduction activity of Hoxc8 proteins, and further suggest that the small peptide could serve as a therapeutic delivery vehicle for large cargo proteins.« less

Better Targeting, Better Efficiency for Wide-Scale Neuronal Transduction with the Synapsin Promoter and AAV-PHP.B

PubMed Central

Jackson, Kasey L.; Dayton, Robert D.; Deverman, Benjamin E.; Klein, Ronald L.

2016-01-01

Widespread genetic modification of cells in the central nervous system (CNS) with a viral vector has become possible and increasingly more efficient. We previously applied an AAV9 vector with the cytomegalovirus/chicken beta-actin (CBA) hybrid promoter and achieved wide-scale CNS transduction in neonatal and adult rats. However, this method transduces a variety of tissues in addition to the CNS. Thus we studied intravenous AAV9 gene transfer with a synapsin promoter to better target the neurons. We noted in systematic comparisons that the synapsin promoter drives lower level expression than does the CBA promoter. The engineered adeno-associated virus (AAV)-PHP.B serotype was compared with AAV9, and AAV-PHP.B did enhance the efficiency of expression. Combining the synapsin promoter with AAV-PHP.B could therefore be advantageous in terms of combining two refinements of targeting and efficiency. Wide-scale expression was used to model a disease with widespread pathology. Vectors encoding the amyotrophic lateral sclerosis (ALS)-related protein transactive response DNA-binding protein, 43 kDa (TDP-43) with the synapsin promoter and AAV-PHP.B were used for efficient CNS-targeted TDP-43 expression. Intracerebroventricular injections were also explored to limit TDP-43 expression to the CNS. The neuron-selective promoter and the AAV-PHP.B enhanced gene transfer and ALS disease modeling in adult rats. PMID:27867348

Better Targeting, Better Efficiency for Wide-Scale Neuronal Transduction with the Synapsin Promoter and AAV-PHP.B.

PubMed

Jackson, Kasey L; Dayton, Robert D; Deverman, Benjamin E; Klein, Ronald L

2016-01-01

Widespread genetic modification of cells in the central nervous system (CNS) with a viral vector has become possible and increasingly more efficient. We previously applied an AAV9 vector with the cytomegalovirus/chicken beta-actin (CBA) hybrid promoter and achieved wide-scale CNS transduction in neonatal and adult rats. However, this method transduces a variety of tissues in addition to the CNS. Thus we studied intravenous AAV9 gene transfer with a synapsin promoter to better target the neurons. We noted in systematic comparisons that the synapsin promoter drives lower level expression than does the CBA promoter. The engineered adeno-associated virus (AAV)-PHP.B serotype was compared with AAV9, and AAV-PHP.B did enhance the efficiency of expression. Combining the synapsin promoter with AAV-PHP.B could therefore be advantageous in terms of combining two refinements of targeting and efficiency. Wide-scale expression was used to model a disease with widespread pathology. Vectors encoding the amyotrophic lateral sclerosis (ALS)-related protein transactive response DNA-binding protein, 43 kDa (TDP-43) with the synapsin promoter and AAV-PHP.B were used for efficient CNS-targeted TDP-43 expression. Intracerebroventricular injections were also explored to limit TDP-43 expression to the CNS. The neuron-selective promoter and the AAV-PHP.B enhanced gene transfer and ALS disease modeling in adult rats.

Exploring transduction mechanisms of protein transduction domains (PTDs) in living cells utilizing single-quantum dot tracking (SQT) technology.

PubMed

Suzuki, Yasuhiro

2012-01-01

Specific protein domains known as protein transduction domains (PTDs) can permeate cell membranes and deliver proteins or bioactive materials into living cells. Various approaches have been applied for improving their transduction efficacy. It is, therefore, crucial to clarify the entry mechanisms and to identify the rate-limiting steps. Because of technical limitations for imaging PTD behavior on cells with conventional fluorescent-dyes, how PTDs enter the cells has been a topic of much debate. Utilizing quantum dots (QDs), we recently tracked the behavior of PTD that was derived from HIV-1 Tat (TatP) in living cells at the single-molecule level with 7-nm special precision. In this review article, we initially summarize the controversy on TatP entry mechanisms; thereafter, we will focus on our recent findings on single-TatP-QD tracking (SQT), to identify the major sequential steps of intracellular delivery in living cells and to discuss how SQT can easily provide direct information on TatP entry mechanisms. As a primer for SQT study, we also discuss the latest findings on single particle tracking of various molecules on the plasma membrane. Finally, we discuss the problems of QDs and the challenges for the future in utilizing currently available QD probes for SQT. In conclusion, direct identification of the rate-limiting steps of PTD entry with SQT should dramatically improve the methods for enhancing transduction efficiency.

Vertically Aligned Graphene Sheets Membrane for Highly Efficient Solar Thermal Generation of Clean Water.

PubMed

Zhang, Panpan; Li, Jing; Lv, Lingxiao; Zhao, Yang; Qu, Liangti

2017-05-23

Efficient utilization of solar energy for clean water is an attractive, renewable, and environment friendly way to solve the long-standing water crisis. For this task, we prepared the long-range vertically aligned graphene sheets membrane (VA-GSM) as the highly efficient solar thermal converter for generation of clean water. The VA-GSM was prepared by the antifreeze-assisted freezing technique we developed, which possessed the run-through channels facilitating the water transport, high light absorption capacity for excellent photothermal transduction, and the extraordinary stability in rigorous conditions. As a result, VA-GSM has achieved average water evaporation rates of 1.62 and 6.25 kg m -2 h -1 under 1 and 4 sun illumination with a superb solar thermal conversion efficiency of up to 86.5% and 94.2%, respectively, better than that of most carbon materials reported previously, which can efficiently produce the clean water from seawater, common wastewater, and even concentrated acid and/or alkali solutions.

A Simple Method to Increase the Transduction Efficiency of Single-Stranded Adeno-Associated Virus Vectors In Vitro and In Vivo

PubMed Central

Ma, Wenqin; Li, Baozheng; Ling, Chen; Jayandharan, Giridhara R.; Byrne, Barry J.

2011-01-01

Abstract We have recently shown that co-administration of conventional single-stranded adeno-associated virus 2 (ssAAV2) vectors with self-complementary (sc) AAV2-protein phosphatase 5 (PP5) vectors leads to a significant increase in the transduction efficiency of ssAAV2 vectors in human cells in vitro as well as in murine hepatocytes in vivo. In the present study, this strategy has been further optimized by generating a mixed population of ssAAV2-EGFP and scAAV2-PP5 vectors at a 10:1 ratio to achieve enhanced green fluorescent protein (EGFP) transgene expression at approximately 5- to 10-fold higher efficiency, both in vitro and in vivo. This simple coproduction method should be adaptable to any ssAAV serotype vector containing transgene cassettes that are too large to be encapsidated in scAAV vectors. PMID:21219084

Aptamer modification improves the adenoviral transduction of malignant glioma cells.

PubMed

Chen, Hao; Zheng, Xiaojing; Di, BingYan; Wang, Dongyang; Zhang, Yaling; Xia, Haibin; Mao, Qinwen

2013-12-01

Adenovirus has shown increasing promise in the gene-viral therapy for glioblastoma, a treatment strategy that relies on the delivery of viruses or transgenes into tumor cells. However, targeting of adenovirus to human glioblastoma remains a challenge due to the low expression level of coxsackie and adenovirus receptor (CAR) in glioma cells. Aptamers are small and highly structured single-stranded oligonucleotides that bind at high affinity to a target molecule, and are good candidates for targeted imaging and therapy. In this study, to construct an aptamer-modified Ad5, we first genetically modified the HVR5 of Ad hexon by biotin acceptor peptide (BAP), which would be metabolically biotinylated during production in HEK293 cells, and then attached the biotin labeled aptamer to the modified Ad through avidin–biotin binding. The aptamers used in this study includes AS1411 and GBI-10. The former is a DNA aptamer that can bind to nucleolin, a nuclear matrix protein found on the surface of cancer cells. The latter is a DNA aptamer that can recognize the extracellular matrix protein tenascin-C on the surface of human glioblastoma cells. To examine if aptamer-modification of the hexon protein could improve the adenoviral transduction efficiency, a glioblastoma cell line, U251, was transduced with aptamer-modified Ads. The transduction efficiency of AS1411- or GBI-10-modified Ad was approximately 4.1-fold or 5.2-fold higher than that of the control. The data indicated that aptamer modified adenovirus would be a useful tool for cancer gene therapy. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Early transduction produces highly functional chimeric antigen receptor-modified virus-specific T-cells with central memory markers: a Production Assistant for Cell Therapy (PACT) translational application.

PubMed

Sun, Jiali; Huye, Leslie E; Lapteva, Natalia; Mamonkin, Maksim; Hiregange, Manasa; Ballard, Brandon; Dakhova, Olga; Raghavan, Darshana; Durett, April G; Perna, Serena K; Omer, Bilal; Rollins, Lisa A; Leen, Ann M; Vera, Juan F; Dotti, Gianpietro; Gee, Adrian P; Brenner, Malcolm K; Myers, Douglas G; Rooney, Cliona M

2015-01-01

Virus-specific T-cells (VSTs) proliferate exponentially after adoptive transfer into hematopoietic stem cell transplant (HSCT) recipients, eliminate virus infections, then persist and provide long-term protection from viral disease. If VSTs behaved similarly when modified with tumor-specific chimeric antigen receptors (CARs), they should have potent anti-tumor activity. This theory was evaluated by Cruz et al. in a previous clinical trial with CD19.CAR-modified VSTs, but there was little apparent expansion of these cells in patients. In that study, VSTs were gene-modified on day 19 of culture and we hypothesized that by this time, sufficient T-cell differentiation may have occurred to limit the subsequent proliferative capacity of the transduced T-cells. To facilitate the clinical testing of this hypothesis in a project supported by the NHLBI-PACT mechanism, we developed and optimized a good manufacturing practices (GMP) compliant method for the early transduction of VSTs directed to Epstein-Barr virus (EBV), Adenovirus (AdV) and cytomegalovirus (CMV) using a CAR directed to the tumor-associated antigen disialoganglioside (GD2). Ad-CMVpp65-transduced EBV-LCLs effectively stimulated VSTs directed to all three viruses (triVSTs). Transduction efficiency on day three was increased in the presence of cytokines and high-speed centrifugation of retroviral supernatant onto retronectin-coated plates, so that under optimal conditions up to 88% of tetramer-positive VSTs expressed the GD2.CAR. The average transduction efficiency of early-and late transduced VSTs was 55 ± 4% and 22 ± 5% respectively, and early-transduced VSTs maintained higher frequencies of T cells with central memory or intermediate memory phenotypes. Early-transduced VSTs also had higher proliferative capacity and produced higher levels of TH1 cytokines IL-2, TNF-α, IFN-γ, MIP-1α, MIP-1β and other cytokines in vitro. We developed a rapid and GMP compliant method for the early transduction of

Neuropilins are positive regulators of Hedgehog signal transduction

PubMed Central

Hillman, R. Tyler; Feng, Brian Y.; Ni, Jun; Woo, Wei-Meng; Milenkovic, Ljiljana; Hayden Gephart, Melanie G.; Teruel, Mary N.; Oro, Anthony E.; Chen, James K.; Scott, Matthew P.

2011-01-01

The Hedgehog (Hh) pathway is essential for vertebrate embryogenesis, and excessive Hh target gene activation can cause cancer in humans. Here we show that Neuropilin 1 (Nrp1) and Nrp2, transmembrane proteins with roles in axon guidance and vascular endothelial growth factor (VEGF) signaling, are important positive regulators of Hh signal transduction. Nrps are expressed at times and locations of active Hh signal transduction during mouse development. Using cell lines lacking key Hh pathway components, we show that Nrps mediate Hh transduction between activated Smoothened (Smo) protein and the negative regulator Suppressor of Fused (SuFu). Nrp1 transcription is induced by Hh signaling, and Nrp1 overexpression increases maximal Hh target gene activation, indicating the existence of a positive feedback circuit. The regulation of Hh signal transduction by Nrps is conserved between mammals and bony fish, as we show that morpholinos targeting the Nrp zebrafish ortholog nrp1a produce a specific and highly penetrant Hh pathway loss-of-function phenotype. These findings enhance our knowledge of Hh pathway regulation and provide evidence for a conserved nexus between Nrps and this important developmental signaling system. PMID:22051878

Unrestricted Hepatocyte Transduction with Adeno-Associated Virus Serotype 8 Vectors in Mice

PubMed Central

Nakai, Hiroyuki; Fuess, Sally; Storm, Theresa A.; Muramatsu, Shin-ichi; Nara, Yuko; Kay, Mark A.

2005-01-01

Recombinant adeno-associated virus (rAAV) vectors can mediate long-term stable transduction in various target tissues. However, with rAAV serotype 2 (rAAV2) vectors, liver transduction is confined to only a small portion of hepatocytes even after administration of extremely high vector doses. In order to investigate whether rAAV vectors of other serotypes exhibit similar restricted liver transduction, we performed a dose-response study by injecting mice with β-galactosidase-expressing rAAV1 and rAAV8 vectors via the portal vein. The rAAV1 vector showed a blunted dose-response similar to that of rAAV2 at high doses, while the rAAV8 vector dose-response remained unchanged at any dose and ultimately could transduce all the hepatocytes at a dose of 7.2 × 1012 vector genomes/mouse without toxicity. This indicates that all hepatocytes have the ability to process incoming single-stranded vector genomes into duplex DNA. A single tail vein injection of the rAAV8 vector was as efficient as portal vein injection at any dose. In addition, intravascular administration of the rAAV8 vector at a high dose transduced all the skeletal muscles throughout the body, including the diaphragm, the entire cardiac muscle, and substantial numbers of cells in the pancreas, smooth muscles, and brain. Thus, rAAV8 is a robust vector for gene transfer to the liver and provides a promising research tool for delivering genes to various target organs. In addition, the rAAV8 vector may offer a potential therapeutic agent for various diseases affecting nonhepatic tissues, but great caution is required for vector spillover and tight control of tissue-specific gene expression. PMID:15596817

Setting the standards for signal transduction research.

PubMed

Saez-Rodriguez, Julio; Alexopoulos, Leonidas G; Stolovitzky, Gustavo

2011-02-15

Major advances in high-throughput technology platforms, coupled with increasingly sophisticated computational methods for systematic data analysis, have provided scientists with tools to better understand the complexity of signaling networks. In this era of massive and diverse data collection, standardization efforts that streamline data gathering, analysis, storage, and sharing are becoming a necessity. Here, we give an overview of current technologies to study signal transduction. We argue that along with the opportunities the new technologies open, their heterogeneous nature poses critical challenges for data handling that are further increased when data are to be integrated in mathematical models. Efficient standardization through markup languages and data annotation is a sine qua non condition for a systems-level analysis of signaling processes. It remains to be seen the extent to which and the speed at which the emerging standardization efforts will be embraced by the signaling community.

Improvement in adenoviral gene transfer efficiency after preincubation at +37 degrees C in vitro and in vivo.

PubMed

Kossila, Maija; Jauhiainen, Suvi; Laukkanen, Mikko O; Lehtolainen, Pauliina; Jääskeläinen, Maiju; Turunen, Päivi; Loimas, Sami; Wahlfors, Jarmo; Ylä-Herttuala, Seppo

2002-01-01

Adenovirus is a widely used vector in gene transfer experiments because it produces high transduction efficiency in vitro and in vivo by means of the coxsackie-adenovirus receptor (CAR) and major histocompatibility complex (MHC) class I alpha-2 domain. Adenoviral gene transfer efficiency has been reported to correlate with cellular CAR expression. We report here a simple method to increase adenoviral gene transfer efficiency in cells that do not express high levels of CAR: preincubation of adenovirus for 30-40 minutes at +37 degrees C significantly increased the transduction efficiency in vitro in CHO and BALB/3T3 cells, in which CAR is expressed at very low levels. Increased transduction efficiency of preincubated adenovirus was also detected in vivo in rat brain tissue. In addition, we found that adenoviruses were rapidly inactivated in human serum in a complement-independent manner, whereas fetal bovine serum (FBS) had hardly any effects on the viral infectivity. We conclude that preincubation of adenoviral vectors at +37 degrees C may substantially increase gene transfer efficiency in applications in which target cells do not express high levels of CAR.

Acoustic waves improves retroviral transduction in human retinal stem cells.

PubMed

Peng, Chi-Hsien; Woung, Lin-Chunh; Lu, Kai-Hsi; Tsai, Ching-Yao; Lee, Shou-Dong; Huang, Chi-Shan; Lin, Tai-Chi; Chien, Ke-Hung; Hwang, De-Kuang

2018-06-22

The plasticity of retinal stem cells (RSCs), a type of cells that can differentiate into neuron cells and photoreceptor cells, endows them with potential therapeutic properties that can be applied to regenerative medicine. Gene modification of these stem cells before trans-differentiation and transplantation enhances their survival and increases their therapeutic function. The different ways to effectively deliver gene into RSCs are still discussed. This study aimed to use the acoustic waves to improve the efficacy of gene delivery for RSCs. RSCs were obtained from non-fetal human ocular pigmented ciliary margin tissues. The enhanced green fluorescent protein-encoded murine stem cell retroviruses (MSCV) were prepared and used to infect RSCs. Glass chambers containing RSCs, retroviruses, and various concentrations of polybrene (0, 0.8, 2, 4 and 8 μg/mL) were exposed under 20 or 25 Vp-p ultrasonic standing wave fields (USWF) for 5 min. The percentage of green fluorescent protein positive cells in each sample was calculated and compared to test the efficacy of gene transduction. Our results showed that the efficiency of gene transduction by MSCV infection was enhanced following the concentration of polybrene and the energy of USWF. The percentage of green fluorescent protein positive cells was significantly higher in chambers that contained 8 μg/mL of polybrene and was exposed to 20Vp-p of USWF for 5 min. In addition, the percentage increased in chambers contained 2, 4 and 8 μg/mL of polybrene when they were exposed to 25Vp-p of USWF. Comparing to those did not treated with ultrasound, the efficiency of retroviral transduction to RSCs increased 4-fold after exposed to USWF for 5 min. We demonstrated the ability of ultrasound standing waves to improve retroviral transduction into RSCs. We believe that this may be applied to the experimental designs of future studies and may have possible therapeutic uses. Copyright © 2018. Published by Elsevier Taiwan LLC.

Colored Petri net modeling and simulation of signal transduction pathways.

PubMed

Lee, Dong-Yup; Zimmer, Ralf; Lee, Sang Yup; Park, Sunwon

2006-03-01

Presented herein is a methodology for quantitatively analyzing the complex signaling network by resorting to colored Petri nets (CPN). The mathematical as well as Petri net models for two basic reaction types were established, followed by the extension to a large signal transduction system stimulated by epidermal growth factor (EGF) in an application study. The CPN models based on the Petri net representation and the conservation and kinetic equations were used to examine the dynamic behavior of the EGF signaling pathway. The usefulness of Petri nets is demonstrated for the quantitative analysis of the signal transduction pathway. Moreover, the trade-offs between modeling capability and simulation efficiency of this pathway are explored, suggesting that the Petri net model can be invaluable in the initial stage of building a dynamic model.

Repeat Transduction in the Mouse Lung by Using Adeno-Associated Virus Vectors with Different Serotypes

PubMed Central

Halbert, Christine L.; Rutledge, Elizabeth A.; Allen, James M.; Russell, David W.; Miller, A. Dusty

2000-01-01

Vectors derived from adeno-associated virus type 2 (AAV2) promote gene transfer and expression in the lung; however, we have found that while gene expression can persist for at least 8 months in mice, it was reduced dramatically in rabbits over a period of 2 months. The efficiency and persistence of AAV2-mediated gene expression in the human lung have yet to be determined, but it seems likely that readministration will be necessary over the lifetime of an individual. Unfortunately, we have found that transduction by a second administration of an AAV2 vector is blocked, presumably due to neutralizing antibodies generated in response to the primary vector exposure. Here, we have explored the use of AAV2 vectors pseudotyped with capsid proteins from AAV serotypes 2, 3, and 6 for readministration in the mouse lung. We found that an AAV6 vector transduced airway epithelial and alveolar cells in the lung at rates that were at least as high as those of AAV2 pseudotype vectors, while transduction rates mediated by AAV3 were much lower. AAV6 pseudotype vector transduction was unaffected by prior administration of an AAV2 or AAV3 vector, and transduction by an AAV2 pseudotype vector was unaffected by prior AAV6 vector administration, showing that cross-reactive neutralizing antibodies against AAV2 and AAV6 are not generated in mice. Interestingly, while prior administration of an AAV2 vector completely blocked transduction by a second AAV2 pseudotype vector, prior administration of an AAV6 vector only partially inhibited transduction by a second administration of an AAV6 pseudotype vector. Analysis of sera obtained from mice and humans showed that AAV6 is less immunogenic than AAV2, which helps explain this finding. These results support the development of AAV6 vectors for lung gene therapy both alone and in combination with AAV2 vectors. PMID:10627564

Enrichment of human hematopoietic stem/progenitor cells facilitates transduction for stem cell gene therapy.

PubMed

Baldwin, Kismet; Urbinati, Fabrizia; Romero, Zulema; Campo-Fernandez, Beatriz; Kaufman, Michael L; Cooper, Aaron R; Masiuk, Katelyn; Hollis, Roger P; Kohn, Donald B

2015-05-01

Autologous hematopoietic stem cell (HSC) gene therapy for sickle cell disease has the potential to treat this illness without the major immunological complications associated with allogeneic transplantation. However, transduction efficiency by β-globin lentiviral vectors using CD34-enriched cell populations is suboptimal and large vector production batches may be needed for clinical trials. Transducing a cell population more enriched for HSC could greatly reduce vector needs and, potentially, increase transduction efficiency. CD34(+) /CD38(-) cells, comprising ∼1%-3% of all CD34(+) cells, were isolated from healthy cord blood CD34(+) cells by fluorescence-activated cell sorting and transduced with a lentiviral vector expressing an antisickling form of beta-globin (CCL-β(AS3) -FB). Isolated CD34(+) /CD38(-) cells were able to generate progeny over an extended period of long-term culture (LTC) compared to the CD34(+) cells and required up to 40-fold less vector for transduction compared to bulk CD34(+) preparations containing an equivalent number of CD34(+) /CD38(-) cells. Transduction of isolated CD34(+) /CD38(-) cells was comparable to CD34(+) cells measured by quantitative PCR at day 14 with reduced vector needs, and average vector copy/cell remained higher over time for LTC initiated from CD34(+) /38(-) cells. Following in vitro erythroid differentiation, HBBAS3 mRNA expression was similar in cultures derived from CD34(+) /CD38(-) cells or unfractionated CD34(+) cells. In vivo studies showed equivalent engraftment of transduced CD34(+) /CD38(-) cells when transplanted in competition with 100-fold more CD34(+) /CD38(+) cells. This work provides initial evidence for the beneficial effects from isolating human CD34(+) /CD38(-) cells to use significantly less vector and potentially improve transduction for HSC gene therapy. © 2015 AlphaMed Press.

Unrevealed part of myosin's powerstroke accounts for high efficiency of muscle contraction.

PubMed

Bibó, András; Károlyi, György; Kovács, Mihály

2017-09-01

Myosin II, the motor protein driving muscle contraction, uses energy of ATP hydrolysis to produce movement along actin. The key step of energy transduction is the powerstroke, involving rotation of myosin's lever while myosin is attached to actin. Macroscopic measurements indicated high thermodynamic efficiency for energy conversion. However, single-molecule experiments indicated lower efficiency, provoking a long-standing discrepancy. Based on the Fluctuation-Dissipation Theorem, we built a sufficiently detailed but low degree-of-freedom model reconstructing the entire mechanoenzymatic cycle. We show that a high axial stiffness of the lever during an initial, experimentally yet unrevealed part of the powerstroke results in a short-time, ratchet-like Kramers effect, and is responsible for the missing efficiency. The second part of the powerstroke is an Eyring-like relaxation that dominantly contributes to lever rotation, but produces only a minor part of the work. The model reveals the structural background of myosin's capability to function as a robust molecular engine and a very precise load sensor as well. Our model also suggests an explanation for the malfunction of myosins harboring mutations that lead to hypertrophic cardiomyopathies with most severe clinical prognosis. The model explains how a force-transmitting device within a biological motor can enable high energetic efficiency. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel approaches to optomechanical transduction

NASA Astrophysics Data System (ADS)

Cernotik, Ondrej; Hammerer, Klemens

In recent years, mechanical oscillators received attention as a promising tool for frequency conversion between microwaves and light. A general, bi-directional transducer with high efficiency is still far from reach of current technology; finding new strategies for optomechanical transduction allows us to relax the requirements and bring these systems closer to an experimental realization. An interesting example is generation of entanglement between two superconducting qubits using measurement and postselection. Here, the mechanical oscillators interacts directly with the superconducting transmon qubit in such a way that it feels a qubit-state dependent force. This force can then be read out using a cavity field; reading out two such systems sequentially realizes an effective total spin measurement. Starting from a suitable initial state and employing postselection, entanglement can be generated. Another interesting approach is to use an array of optomechanical transducers in which the output fields of one transducer are fed into the input of the next. The periodicity of the array results in a joint dispersion relation for the propagating microwave and optical fields. The resulting structure can be used to control the conversion bandwidth and forward and backward scattering.

Gene transduction in mammalian cells using Bombyx mori nucleopolyhedrovirus assisted by glycoprotein 64 of Autographa californica multiple nucleopolyhedrovirus.

PubMed

Kato, Tatsuya; Sugioka, Saki; Itagaki, Kohei; Park, Enoch Y

2016-08-26

Autographa californica multiple nucleopolyhedrovirus (AcMNPV), an alphabaculovirus, has been widely utilized for protein expression in not only insect cells but also mammalian cells. AcMNPV is closely related to Bombyx mori nucleopolyhedrovirus (BmNPV), and nucleotide sequences of AcMNPV genes have high similarity with those of BmNPV. However, the transduction of BmNPV into mammalian cells has not been reported. In this study, we constructed a recombinant BmNPV (BmNPVΔbgp/AcGP64/EGFP) whose surface 64 kDa glycoprotein (BmGP64) was substituted with that from AcMNPV (AcGP64). BmNPVΔbgp/AcGP64/EGFP also carried an EGFP gene under the control of the CMV promoter. BmNPVΔbgp/AcGP64/EGFP successfully transduced HEK293T cells. In comparison, a control construct (BmNPVΔbgp/BmGP64/EGFP) which possessed BmGP64 instead of AcGP64 did not express EGFP in HEK293T cells. The transduction efficiency of BmNPVΔbgp/AcGP64/EGFP was lower than that of an AcMNPV based-BacMam GFP transduction control. This result indicates that AcGP64 facilitates BmNPV transduction into HEK293T cells. BmNPV can be prepared easily on a large scale because BmNPV can infect silkworm larvae without any special equipment, even though specific diet is needed for silkworm rearing. BmNPV gene transduction into mammalian cells can potentially be applied easily for gene delivery into mammalian cells.

Lipid and cationic polymer based transduction of botulinum holotoxin, or toxin protease alone, extends the target cell range and improves the efficiency of intoxication.

PubMed

Kuo, Chueh-Ling; Oyler, George; Shoemaker, Charles B

2010-01-01

Botulinum neurotoxin (BoNT) heavy chain (Hc) facilitates receptor-mediated endocytosis into neuronal cells and transport of the light chain (Lc) protease to the cytosol where neurotransmission is inhibited as a result of SNARE protein cleavage. Here we show that the role of BoNT Hc in cell intoxication can be replaced by commercial lipid-based and polycationic polymer DNA transfection reagents. BoNT "transduction" by these reagents permits efficient intoxication of neuronal cells as well as some non-neuronal cell lines normally refractory to BoNT. Surprisingly, the reagents facilitate delivery of recombinant BoNT Lc protease to the cytosol of both neuronal and non-neuronal cells in the absence of BoNT Hc, and with sensitivities approaching that of BoNT holotoxin. Transduction of BoNT, as with natural intoxication, is inhibited by bafilomycin A1, methylamine and ammonium chloride indicating that both pathways require endosome acidification. DNA transfection reagents facilitate intoxication by holotoxins, or isolated Lc proteases, of all three BoNT serotypes tested (A, B, E). These results suggest that lipid and cationic polymer transfection reagents facilitate cytosolic delivery of BoNT holotoxins and isolated Lc proteases by an endosomal uptake pathway.

The efficiency of cellular energy transduction and its implications for obesity.

PubMed

Harper, Mary-Ellen; Green, Katherine; Brand, Martin D

2008-01-01

We assess the existence, mechanism, and functions of less-than-maximal coupling efficiency of mitochondrial oxidative phosphorylation and its potential as a target for future antiobesity interventions. Coupling efficiency is the proportion of oxygen consumption used to make adenosine triphosphate (ATP) and do useful work. High coupling efficiency may lead to fat deposition; low coupling efficiency to a decrease in fat stores. We review obligatory and facultative energy expenditure and the role of a futile cycle of proton pumping and proton leak across the mitochondrial inner membrane in dissipating energy. Basal proton conductance is catalyzed primarily by the adenine nucleotide translocase but can be mimicked by chemical uncouplers. Inducible proton conductance is catalyzed by specific uncoupling proteins. We discuss the opportunities and pitfalls of targeting these processes as a treatment for obesity by decreasing coupling efficiency and increasing energy expenditure, either directly or through central mechanisms of energy homeostasis.

Lipid rafts generate digital-like signal transduction in cell plasma membranes.

PubMed

Suzuki, Kenichi G N

2012-06-01

Lipid rafts are meso-scale (5-200 nm) cell membrane domains where signaling molecules assemble and function. However, due to their dynamic nature, it has been difficult to unravel the mechanism of signal transduction in lipid rafts. Recent advanced imaging techniques have revealed that signaling molecules are frequently, but transiently, recruited to rafts with the aid of protein-protein, protein-lipid, and/or lipid-lipid interactions. Individual signaling molecules within the raft are activated only for a short period of time. Immobilization of signaling molecules by cytoskeletal actin filaments and scaffold proteins may facilitate more efficient signal transmission from rafts. In this review, current opinions of how the transient nature of molecular interactions in rafts generates digital-like signal transduction in cell membranes, and the benefits this phenomenon provides, are discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rapid lentiviral transduction preserves the engraftment potential of Fanca(-/-) hematopoietic stem cells.

PubMed

Müller, Lars U W; Milsom, Michael D; Kim, Mi-Ok; Schambach, Axel; Schuesler, Todd; Williams, David A

2008-06-01

Fanconi anemia (FA) is a rare recessive syndrome, characterized by congenital anomalies, bone marrow failure, and predisposition to cancer. Two earlier clinical trials utilizing gamma-retroviral vectors for the transduction of autologous FA hematopoietic stem cells (HSCs) required extensive in vitro manipulation and failed to achieve detectable long-term engraftment of transduced HSCs. As a strategy for minimizing ex vivo manipulation, we investigated the use of a "rapid" lentiviral transduction protocol in a murine Fanca(-/-) model. Importantly, while this and most murine models of FA fail to completely mimic the human hematopoietic phenotype, we observed a high incidence of HSC transplant engraftment failure and low donor chimerism after conventional transduction (CT) of Fanca(-/-) donor cells. In contrast, rapid transduction (RT) of Fanca(-/-) HSCs preserved engraftment to the level achieved in wild-type cells, resulting in long-term multilineage engraftment of gene-modified cells. We also demonstrate the correction of the characteristic hypersensitivity of FA cells against the cross-linking agent mitomycin C (MMC), and provide evidence for the advantage of using pharmacoselection as a means of further increasing gene-modified cells after RT. Collectively, these data support the use of rapid lentiviral transduction for gene therapy in FA.

Energy Equivalence of Information in the Mitochondrion and the Thermodynamic Efficiency of ATP Synthase.

PubMed

Matta, Chérif F; Massa, Lou

2015-09-01

Half a century ago, Johnson and Knudsen resolved the puzzle of the apparent low efficiency of the kidney (∼ 0.5%) compared to most other bodily organs (∼ 40%) by taking into account the entropic cost of ion sorting, the principal function of this organ. Similarly, it is shown that the efficiency of energy transduction of the chemiosmotic proton-motive force by ATP synthase is closer to 90% instead of the oft-quoted textbook value of only 60% when information theoretic considerations are applied to the mitochondrion. This high efficiency is consistent with the mechanical energy transduction of ATP synthase known to be close to the 100% thermodynamic limit. It would have been wasteful for evolution to maximize the mechanical energy transduction to 100% while wasting 40% of the chemiosmotic free energy in the conversion of the proton-motive force into mechanical work before being captured as chemical energy in adenosine 5'-triphosphate.

Extending the Host Range of Bacteriophage Particles for DNA Transduction.

PubMed

Yosef, Ido; Goren, Moran G; Globus, Rea; Molshanski-Mor, Shahar; Qimron, Udi

2017-06-01

A major limitation in using bacteriophage-based applications is their narrow host range. Approaches for extending the host range have focused primarily on lytic phages in hosts supporting their propagation rather than approaches for extending the ability of DNA transduction into phage-restrictive hosts. To extend the host range of T7 phage for DNA transduction, we have designed hybrid particles displaying various phage tail/tail fiber proteins. These modular particles were programmed to package and transduce DNA into hosts that restrict T7 phage propagation. We have also developed an innovative generalizable platform that considerably enhances DNA transfer into new hosts by artificially selecting tails that efficiently transduce DNA. In addition, we have demonstrated that the hybrid particles transduce desired DNA into desired hosts. This study thus critically extends and improves the ability of the particles to transduce DNA into novel phage-restrictive hosts, providing a platform for myriad applications that require this ability. Copyright © 2017 Elsevier Inc. All rights reserved.

The Membrane and Lipids as Integral Participants in Signal Transduction: Lipid Signal Transduction for the Non-Lipid Biochemist

ERIC Educational Resources Information Center

Eyster, Kathleen M.

2007-01-01

Reviews of signal transduction have often focused on the cascades of protein kinases and protein phosphatases and their cytoplasmic substrates that become activated in response to extracellular signals. Lipids, lipid kinases, and lipid phosphatases have not received the same amount of attention as proteins in studies of signal transduction.…

CRISPR-Cas-Mediated Phage Resistance Enhances Horizontal Gene Transfer by Transduction.

PubMed

Watson, Bridget N J; Staals, Raymond H J; Fineran, Peter C

2018-02-13

A powerful contributor to prokaryotic evolution is horizontal gene transfer (HGT) through transformation, conjugation, and transduction, which can be advantageous, neutral, or detrimental to fitness. Bacteria and archaea control HGT and phage infection through CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) adaptive immunity. Although the benefits of resisting phage infection are evident, this can come at a cost of inhibiting the acquisition of other beneficial genes through HGT. Despite the ability of CRISPR-Cas to limit HGT through conjugation and transformation, its role in transduction is largely overlooked. Transduction is the phage-mediated transfer of bacterial DNA between cells and arguably has the greatest impact on HGT. We demonstrate that in Pectobacterium atrosepticum , CRISPR-Cas can inhibit the transduction of plasmids and chromosomal loci. In addition, we detected phage-mediated transfer of a large plant pathogenicity genomic island and show that CRISPR-Cas can inhibit its transduction. Despite these inhibitory effects of CRISPR-Cas on transduction, its more common role in phage resistance promotes rather than diminishes HGT via transduction by protecting bacteria from phage infection. This protective effect can also increase transduction of phage-sensitive members of mixed populations. CRISPR-Cas systems themselves display evidence of HGT, but little is known about their lateral dissemination between bacteria and whether transduction can contribute. We show that, through transduction, bacteria can acquire an entire chromosomal CRISPR-Cas system, including cas genes and phage-targeting spacers. We propose that the positive effect of CRISPR-Cas phage immunity on enhancing transduction surpasses the rarer cases where gene flow by transduction is restricted. IMPORTANCE The generation of genetic diversity through acquisition of DNA is a powerful contributor to microbial evolution and occurs through

Highly efficient gene transfer in naive human T cells with a murine leukemia virus-based vector.

PubMed

Dardalhon, V; Jaleco, S; Rebouissou, C; Ferrand, C; Skander, N; Swainson, L; Tiberghien, P; Spits, H; Noraz, N; Taylor, N

2000-08-01

Retroviral vectors based on the Moloney murine leukemia virus (MuLV) have become the primary tool for gene delivery into hematopoietic cells, but clinical trials have been hampered by low transduction efficiencies. Recently, we and others have shown that gene transfer of MuLV-based vectors into T cells can be significantly augmented using a fibronectin-facilitated protocol. Nevertheless, the relative abilities of naive (CD45RA(+)) and memory (CD45RO(+)) lymphocyte subsets to be transduced has not been assessed. Although naive T cells demonstrate a restricted cytokine profile following antigen stimulation and a decreased susceptibility to infection with human immunodeficiency virus, it was not clear whether they could be efficiently infected with a MuLV vector. This study describes conditions that permitted gene transfer of an enhanced green fluorescent protein-expressing retroviral vector in more than 50% of naive umbilical cord (UC) blood and peripheral blood (PB) T cells following CD3/CD28 ligation. Moreover, treatment of naive T cells with interleukin-7 resulted in the maintenance of a CD45RA phenotype and gene transfer levels approached 20%. Finally, it was determined that parameters for optimal transduction of CD45RA(+) T cells isolated from PB and UC blood differed: transduction of the UC cells was significantly increased by the presence of autologous mononuclear cells (24.5% versus 56.5%). Because naive T cells harbor a receptor repertoire that allows them to respond to novel antigens, the development of protocols targeting their transduction is crucial for gene therapy applications. This approach will also allow the functions of exogenous genes to be evaluated in primary nontransformed naive T cells.

ROS-dependent signal transduction

PubMed Central

Reczek, Colleen R; Chandel, Navdeep S

2014-01-01

Reactive oxygen species (ROS) are no longer viewed as just a toxic by-product of mitochondrial respiration, but are now appreciated for their role in regulating a myriad of cellular signaling pathways. H2O2, a type of ROS, is a signaling molecule that confers target specificity through thiol oxidation. Although redox-dependent signaling has been implicated in numerous cellular processes, the mechanism by which the ROS signal is transmitted to its target protein in the face of highly reactive and abundant antioxidants is not fully understood. In this review of redox-signaling biology, we discuss the possible mechanisms for H2O2-dependent signal transduction. PMID:25305438

Molecular analysis of vector genome structures after liver transduction by conventional and self-complementary adeno-associated viral serotype vectors in murine and nonhuman primate models.

PubMed

Sun, Xun; Lu, You; Bish, Lawrence T; Calcedo, Roberto; Wilson, James M; Gao, Guangping

2010-06-01

Vectors based on several new adeno-associated viral (AAV) serotypes demonstrated strong hepatocyte tropism and transduction efficiency in both small- and large-animal models for liver-directed gene transfer. Efficiency of liver transduction by AAV vectors can be further improved in both murine and nonhuman primate (NHP) animals when the vector genomes are packaged in a self-complementary (sc) format. In an attempt to understand potential molecular mechanism(s) responsible for enhanced transduction efficiency of the sc vector in liver, we performed extensive molecular studies of genome structures of conventional single-stranded (ss) and sc AAV vectors from liver after AAV gene transfer in both mice and NHPs. These included treatment with exonucleases with specific substrate preferences, single-cutter restriction enzyme digestion and polarity-specific hybridization-based vector genome mapping, and bacteriophage phi29 DNA polymerase-mediated and double-stranded circular template-specific rescue of persisted circular genomes. In mouse liver, vector genomes of both genome formats seemed to persist primarily as episomal circular forms, but sc vectors converted into circular forms more rapidly and efficiently. However, the overall differences in vector genome abundance and structure in the liver between ss and sc vectors could not account for the remarkable differences in transduction. Molecular structures of persistent genomes of both ss and sc vectors were significantly more heterogeneous in macaque liver, with noticeable structural rearrangements that warrant further characterizations.

[Transduction peptides, the useful face of a new signaling mechanism].

PubMed

Joliot, Alain; Prochiantz, Alain

2005-03-01

Transduction peptides that cross the plasma membrane of live cells are commonly used for the in vitro and in vivo targeting of hydrophilic drugs into the cell interior. Although this family of peptides has recently increased and will probably continue to do so, the two mainly used peptides are derived from transcription factors. Indeed, TAT is a 12 amino acid long arginine-rich peptide present in the HIV transcription factor, and penetratin - or its variants - corresponds to 16 amino acids that define the highly conserved third helix of the DNA-binding domain (homeodomain) of homeoprotein transcription factors. In this review, we shall recall the different steps that have led to the discovery of transduction peptides and present the most likely hypotheses concerning the mechanisms involved in their internalization. At the risk of being incomplete or, even, biased, we shall concentrate on penetratins and TAT. The reason is that these peptides have been studied for over ten years leading to the edification of robust knowledge regarding their properties. This attitude will not preclude comparisons with other peptides, if necessary. Our goal is to describe the mode of action of these transduction peptides, their range of activity in term of cell types that accept them and cargoes that they can transport, and, also, some of the limitations that one can encounter in their use. Finally, based on the idea that peptide transduction is the technological face of a physiological property of some transcription factors, we shall discuss the putative physiological function of homeoprotein transduction, and, as a consequence, the possibility to use these factors as therapeutic proteins.

naked cuticle targets dishevelled to antagonize Wnt signal transduction

PubMed Central

Rousset, Raphaël; Mack, Judith A.; Wharton, Keith A.; Axelrod, Jeffrey D.; Cadigan, Ken M.; Fish, Matthew P.; Nusse, Roel; Scott, Matthew P.

2001-01-01

In Drosophila embryos the protein Naked cuticle (Nkd) limits the effects of the Wnt signal Wingless (Wg) during early segmentation. nkd loss of function results in segment polarity defects and embryonic death, but how nkd affects Wnt signaling is unknown. Using ectopic expression, we find that Nkd affects, in a cell-autonomous manner, a transduction step between the Wnt signaling components Dishevelled (Dsh) and Zeste-white 3 kinase (Zw3). Zw3 is essential for repressing Wg target-gene transcription in the absence of a Wg signal, and the role of Wg is to relieve this inhibition. Our double-mutant analysis shows that, in contrast to Zw3, Nkd acts when the Wg pathway is active to restrain signal transduction. Yeast two hybrid and in vitro experiments indicate that Nkd directly binds to the basic-PDZ region of Dsh. Specially timed Nkd overexpression is capable of abolishing Dsh function in a distinct signaling pathway that controls planar-cell polarity. Our results suggest that Nkd acts directly through Dsh to limit Wg activity and thus determines how efficiently Wnt signals stabilize Armadillo (Arm)/β-catenin and activate downstream genes. PMID:11274052

Modeling the infection dynamics of bacteriophages in enteric Escherichia coli: estimating the contribution of transduction to antimicrobial gene spread.

PubMed

Volkova, Victoriya V; Lu, Zhao; Besser, Thomas; Gröhn, Yrjö T

2014-07-01

Animal-associated bacterial communities are infected by bacteriophages, although the dynamics of these infections are poorly understood. Transduction by bacteriophages may contribute to transfer of antimicrobial resistance genes, but the relative importance of transduction among other gene transfer mechanisms is unknown. We therefore developed a candidate deterministic mathematical model of the infection dynamics of enteric coliphages in commensal Escherichia coli in the large intestine of cattle. We assumed the phages were associated with the intestine and were predominantly temperate. Model simulations demonstrated how, given the bacterial ecology and infection dynamics, most (>90%) commensal enteric E. coli bacteria may become lysogens of enteric coliphages during intestinal transit. Using the model and the most liberal assumptions about transduction efficiency and resistance gene frequency, we approximated the upper numerical limits ("worst-case scenario") of gene transfer through specialized and generalized transduction in E. coli by enteric coliphages when the transduced genetic segment is picked at random. The estimates were consistent with a relatively small contribution of transduction to lateral gene spread; for example, generalized transduction delivered the chromosomal resistance gene to up to 8 E. coli bacteria/hour within the population of 1.47 × 10(8) E. coli bacteria/liter luminal contents. In comparison, the plasmidic blaCMY-2 gene carried by ~2% of enteric E. coli was transferred by conjugation at a rate at least 1.4 × 10(3) times greater than our generalized transduction estimate. The estimated numbers of transductants varied nonlinearly depending on the ecology of bacteria available for phages to infect, that is, on the assumed rates of turnover and replication of enteric E. coli. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Modeling the Infection Dynamics of Bacteriophages in Enteric Escherichia coli: Estimating the Contribution of Transduction to Antimicrobial Gene Spread

PubMed Central

Lu, Zhao; Besser, Thomas; Gröhn, Yrjö T.

2014-01-01

Animal-associated bacterial communities are infected by bacteriophages, although the dynamics of these infections are poorly understood. Transduction by bacteriophages may contribute to transfer of antimicrobial resistance genes, but the relative importance of transduction among other gene transfer mechanisms is unknown. We therefore developed a candidate deterministic mathematical model of the infection dynamics of enteric coliphages in commensal Escherichia coli in the large intestine of cattle. We assumed the phages were associated with the intestine and were predominantly temperate. Model simulations demonstrated how, given the bacterial ecology and infection dynamics, most (>90%) commensal enteric E. coli bacteria may become lysogens of enteric coliphages during intestinal transit. Using the model and the most liberal assumptions about transduction efficiency and resistance gene frequency, we approximated the upper numerical limits (“worst-case scenario”) of gene transfer through specialized and generalized transduction in E. coli by enteric coliphages when the transduced genetic segment is picked at random. The estimates were consistent with a relatively small contribution of transduction to lateral gene spread; for example, generalized transduction delivered the chromosomal resistance gene to up to 8 E. coli bacteria/hour within the population of 1.47 × 108 E. coli bacteria/liter luminal contents. In comparison, the plasmidic blaCMY-2 gene carried by ∼2% of enteric E. coli was transferred by conjugation at a rate at least 1.4 × 103 times greater than our generalized transduction estimate. The estimated numbers of transductants varied nonlinearly depending on the ecology of bacteria available for phages to infect, that is, on the assumed rates of turnover and replication of enteric E. coli. PMID:24814786

Elementary signaling modes predict the essentiality of signal transduction network components

PubMed Central

2011-01-01

Background Understanding how signals propagate through signaling pathways and networks is a central goal in systems biology. Quantitative dynamic models help to achieve this understanding, but are difficult to construct and validate because of the scarcity of known mechanistic details and kinetic parameters. Structural and qualitative analysis is emerging as a feasible and useful alternative for interpreting signal transduction. Results In this work, we present an integrative computational method for evaluating the essentiality of components in signaling networks. This approach expands an existing signaling network to a richer representation that incorporates the positive or negative nature of interactions and the synergistic behaviors among multiple components. Our method simulates both knockout and constitutive activation of components as node disruptions, and takes into account the possible cascading effects of a node's disruption. We introduce the concept of elementary signaling mode (ESM), as the minimal set of nodes that can perform signal transduction independently. Our method ranks the importance of signaling components by the effects of their perturbation on the ESMs of the network. Validation on several signaling networks describing the immune response of mammals to bacteria, guard cell abscisic acid signaling in plants, and T cell receptor signaling shows that this method can effectively uncover the essentiality of components mediating a signal transduction process and results in strong agreement with the results of Boolean (logical) dynamic models and experimental observations. Conclusions This integrative method is an efficient procedure for exploratory analysis of large signaling and regulatory networks where dynamic modeling or experimental tests are impractical. Its results serve as testable predictions, provide insights into signal transduction and regulatory mechanisms and can guide targeted computational or experimental follow-up studies. The

The thermodynamic efficiency of ATP synthesis in oxidative phosphorylation.

PubMed

Nath, Sunil

2016-12-01

As the chief energy source of eukaryotic cells, it is important to determine the thermodynamic efficiency of ATP synthesis in oxidative phosphorylation (OX PHOS). Previous estimates of the thermodynamic efficiency of this vital process have ranged from Lehninger's original back-of-the-envelope calculation of 38% to the often quoted value of 55-60% in current textbooks of biochemistry, to high values of 90% from recent information theoretic considerations, and reports of realizations of close to ideal 100% efficiencies by single molecule experiments. Hence this problem has been reinvestigated from first principles. The overall thermodynamic efficiency of ATP synthesis in the mitochondrial energy transduction OX PHOS process has been found to lie between 40 and 41% from four different approaches based on a) estimation using structural and biochemical data, b) fundamental nonequilibrium thermodynamic analysis, c) novel insights arising from Nath's torsional mechanism of energy transduction and ATP synthesis, and d) the overall balance of cellular energetics. The torsional mechanism also offers an explanation for the observation of a thermodynamic efficiency approaching 100% in some experiments. Applications of the unique, molecular machine mode of functioning of F 1 F O -ATP synthase involving direct inter-conversion of chemical and mechanical energies in the design and fabrication of novel, man-made mechanochemical devices have been envisaged, and some new ways to exorcise Maxwell's demon have been proposed. It is hoped that analysis of the fundamental problem of energy transduction in OX PHOS from a fresh perspective will catalyze new avenues of research in this interdisciplinary field. Copyright © 2016 Elsevier B.V. All rights reserved.

ROS-dependent signal transduction.

PubMed

Reczek, Colleen R; Chandel, Navdeep S

2015-04-01

Reactive oxygen species (ROS) are no longer viewed as just a toxic by-product of mitochondrial respiration, but are now appreciated for their role in regulating a myriad of cellular signaling pathways. H2O2, a type of ROS, is a signaling molecule that confers target specificity through thiol oxidation. Although redox-dependent signaling has been implicated in numerous cellular processes, the mechanism by which the ROS signal is transmitted to its target protein in the face of highly reactive and abundant antioxidants is not fully understood. In this review of redox-signaling biology, we discuss the possible mechanisms for H2O2-dependent signal transduction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular Analysis of Vector Genome Structures After Liver Transduction by Conventional and Self-Complementary Adeno-Associated Viral Serotype Vectors in Murine and Nonhuman Primate Models

PubMed Central

Sun, Xun; Lu, You; Bish, Lawrence T.; Calcedo, Roberto; Wilson, James M.

2010-01-01

Abstract Vectors based on several new adeno-associated viral (AAV) serotypes demonstrated strong hepatocyte tropism and transduction efficiency in both small- and large-animal models for liver-directed gene transfer. Efficiency of liver transduction by AAV vectors can be further improved in both murine and nonhuman primate (NHP) animals when the vector genomes are packaged in a self-complementary (sc) format. In an attempt to understand potential molecular mechanism(s) responsible for enhanced transduction efficiency of the sc vector in liver, we performed extensive molecular studies of genome structures of conventional single-stranded (ss) and sc AAV vectors from liver after AAV gene transfer in both mice and NHPs. These included treatment with exonucleases with specific substrate preferences, single-cutter restriction enzyme digestion and polarity-specific hybridization-based vector genome mapping, and bacteriophage ϕ29 DNA polymerase-mediated and double-stranded circular template-specific rescue of persisted circular genomes. In mouse liver, vector genomes of both genome formats seemed to persist primarily as episomal circular forms, but sc vectors converted into circular forms more rapidly and efficiently. However, the overall differences in vector genome abundance and structure in the liver between ss and sc vectors could not account for the remarkable differences in transduction. Molecular structures of persistent genomes of both ss and sc vectors were significantly more heterogeneous in macaque liver, with noticeable structural rearrangements that warrant further characterizations. PMID:20113166

The Physiology of Mechanoelectrical Transduction Channels in Hearing

PubMed Central

Fettiplace, Robert; Kim, Kyunghee X.

2014-01-01

Much is known about the mechanotransducer (MT) channels mediating transduction in hair cells of the vertrbrate inner ear. With the use of isolated preparations, it is experimentally feasible to deliver precise mechanical stimuli to individual cells and record the ensuing transducer currents. This approach has shown that small (1–100 nm) deflections of the hair-cell stereociliary bundle are transmitted via interciliary tip links to open MT channels at the tops of the stereocilia. These channels are cation-permeable with a high selectivity for Ca2+; two channels are thought to be localized at the lower end of the tip link, each with a large single-channel conductance that increases from the low- to high-frequency end of the cochlea. Ca2+ influx through open channels regulates their resting open probability, which may contribute to setting the hair cell resting potential in vivo. Ca2+ also controls transducer fast adaptation and force generation by the hair bundle, the two coupled processes increasing in speed from cochlear apex to base. The molecular intricacy of the stereocilary bundle and the transduction apparatus is reflected by the large number of single-gene mutations that are linked to sensorineural deafness, especially those in Usher syndrome. Studies of such mutants have led to the discovery of many of the molecules of the transduction complex, including the tip link and its attachments to the stereociliary core. However, the MT channel protein is still not firmly identified, nor is it known whether the channel is activated by force delivered through accessory proteins or by deformation of the lipid bilayer. PMID:24987009

Dynamic Receptor Team Formation Can Explain the High Signal Transduction Gain in Escherichia coli

NASA Astrophysics Data System (ADS)

Albert, R.; Chiu, Y.; Othmer, H.

2004-05-01

Evolution has provided many organisms with sophisticated sensory systems that enable them to respond to signals in their environment. The response frequently involves alteration in the pattern of movement, such as the chemokinesis of the bacterium Escherichia coli, which swims by rotating its flagella. When rotated counterclockwise (CCW) the flagella coalesce into a propulsive bundle, producing a relatively straight ``run'', and when rotated clockwise (CW) they fly apart, resulting in a ``tumble'' which reorients the cell with little translocation. A stochastic process generates the runs and tumbles, and in a chemoeffector gradient runs that carry the cell in a favorable direction are extended. The overall structure of the signal transduction pathways is well-characterized in E. coli, but important details are still not understood. Only recently has a source of gain in the signal transduction network been identified experimentally, and here we present a mathematical model based on dynamic assembly of receptor teams that can explain this observation.

Cochlear Hair Cell Electrochemistry: Mechanisms for Bidirectional Transduction.

DTIC Science & Technology

1988-06-30

cytoplasm in the cell’s laminated cisternal system. More specifically, we postulate that intracochlear potential gradients associated with acoustic...transduction drive intracellular fluids through an electo-osmotic "pump" formed by the plasma membrane and the morphologically unique laminated cisternal ...laminated cisternal system in the hearing loss measured with brainstem evoked response. The highly polycationic nature of the polyamines suggest their

Generalized transduction: new aspects of the events in the water column

NASA Astrophysics Data System (ADS)

Velimirov, B.; Chiura, H. X.; Kogure, K.

2003-04-01

Virus mediated transfer of genetic elements among bacteria in nature has become a major research topic in the last decade. Along with conjugation and transformation, transduction is a well-known mechanism resulting in horizontal gene transfer in procaryotic organisms. In the case of generalized transduction, all regions of the procaryotic chromosome or other genetic elements in the donor cell are transferred with nearly the same frequency to the recipient. The injection of this DNA induces the generation of stable transductants. Both virulent and temperate phages have the capability to induce general transduction.Within the frame of a study on intergeneric phage-mediated gene transfer between marine bacteria and enteric bacteria, namely an auxotrophic mutant of Escherichia coli (AB1157) we used virus like particles (VLPs) from an oligotrophic marine environment (Mediterranean Sea, West coast of Corsica) and obtained gene transfer frequencies ranging between 10-2 to 10-6 per viral particle. Consequently we had to assume that an important fraction of the VLPs obtained via ultrafiltration (Minitan Ultrafiltration System, Millipore, USA. 30 kDA cut-off filter) from surface seawater have the capability to induce general transduction. In the process of this investigation we made a number of new observations which were not compatible with the concept of general transduction. The obtained transductants were able to produce new VLPs, which had again the capability to induce transduction. In an attempt to characterize these particles we show that their appearance in the experiment was neither related to plaque formation nor to cell lysis and we discuss the concept of transduction in the light of new experimental evidence concerning transducing particles. Furthermore, a preliminary numerical model allowing an estimation of the transduction events, taking place in the water column within a year is presented.

Analysis of cellular signal transduction from an information theoretic approach.

PubMed

Uda, Shinsuke; Kuroda, Shinya

2016-03-01

Signal transduction processes the information of various cellular functions, including cell proliferation, differentiation, and death. The information for controlling cell fate is transmitted by concentrations of cellular signaling molecules. However, how much information is transmitted in signaling pathways has thus far not been investigated. Shannon's information theory paves the way to quantitatively analyze information transmission in signaling pathways. The theory has recently been applied to signal transduction, and mutual information of signal transduction has been determined to be a measure of information transmission. We review this work and provide an overview of how signal transduction transmits informational input and exerts biological output. Copyright © 2015 Elsevier Ltd. All rights reserved.

Viral transduction of the HER2-extracellular domain expands trastuzumab-based photoimmunotherapy for HER2-negative breast cancer cells.

PubMed

Shimoyama, Kyoko; Kagawa, Shunsuke; Ishida, Michihiro; Watanabe, Shinichiro; Noma, Kazuhiro; Takehara, Kiyoto; Tazawa, Hiroshi; Hashimoto, Yuuri; Tanabe, Shunsuke; Matsuoka, Junji; Kobayashi, Hisataka; Fujiwara, Toshiyoshi

2015-02-01

The prognosis of HER2-positive breast cancer has been improved by trastuzumab therapy, which features high specificity and limited side effects. However, trastuzumab-based therapy has shortcomings. Firstly, HER2-targeted therapy is only applicable to HER2-expressing tumors, which comprise only 20-25% of primary breast cancers. Secondly, many patients who initially respond to trastuzumab ultimately develop disease progression. To overcome these problems, we employed virus-mediated HER2 transduction and photoimmunotherapy (PIT) which involves trastuzumab conjugated with a photosensitizer, trastuzumab-IR700, and irradiation of near-infrared light. We hypothesized that the gene transduction technique together with PIT would expand the range of tumor entities suitable for trastuzumab-based therapy and improve its antitumor activity. The HER2-extracellular domain (ECD) was transduced by the adenoviral vector, Ad-HER2-ECD, and PIT with trastuzumab-IR700 was applied in the HER2-negative cancer cells. Ad-HER2-ECD can efficiently transduce HER2-ECD into HER2-negative human cancer cells. PIT with trastuzumab-IR700 induced direct cell membrane destruction of Ad-HER2-ECD-transduced HER2-negative cancer cells. Novel combination of viral transduction of a target antigen and an antibody-based PIT would expand and potentiate molecular-targeted therapy even for target-negative or attenuated cancer cells.

Signal transduction in the footsteps of goethe and schiller.

PubMed

Friedrich, Karlheinz; Lindquist, Jonathan A; Entschladen, Frank; Serfling, Edgar; Thiel, Gerald; Kieser, Arnd; Giehl, Klaudia; Ehrhardt, Christina; Feller, Stephan M; Ullrich, Oliver; Schaper, Fred; Janssen, Ottmar; Hass, Ralf

2009-02-04

The historical town of Weimar in Thuringia, the "green heart of Germany" was the sphere of Goethe and Schiller, the two most famous representatives of German literature's classic era. Not yet entirely as influential as those two cultural icons, the Signal Transduction Society (STS) has nevertheless in the last decade established within the walls of Weimar an annual interdisciplinary Meeting on "Signal Transduction - Receptors, Mediators and Genes", which is well recognized as a most attractive opportunity to exchange results and ideas in the field.The 12th STS Meeting was held from October 28 to 31 and provided a state-of-the-art overview of various areas of signal transduction research in which progress is fast and discussion lively. This report is intended to share with the readers of CCS some highlights of the Meeting Workshops devoted to specific aspects of signal transduction.

Coherent Optomechanical Switch for Motion Transduction Based on Dynamically Localized Mechanical Modes

NASA Astrophysics Data System (ADS)

Fu, Hao; Gong, Zhi-cheng; Yang, Li-ping; Mao, Tian-hua; Sun, Chang-pu; Yi, Su; Li, Yong; Cao, Geng-yu

2018-05-01

We present a coherent switch for motion transduction based on dynamically localized mechanical modes in an optomechanical system consisting of two coupled cantilevers. By placing one of the cantilevers inside a harmonically oscillating optical trap, the effective coupling strength between the degenerate cantilevers can be tuned experimentally. In particular, when the coupling is turned off, we show that mechanical motion becomes tightly bounded to the isolated cantilevers rather than propagating away as a result of destructive Landau-Zener-Stückelberg-like interference. The effect of dynamical localization is adopted to implement a coherent switch, through which the tunneling oscillation is turned on and off with well-preserved phase coherence. We provide a simple yet efficient approach for full control of the coupling between mechanical resonators, which is highly desirable for coherent control of transport phenomena in a coupled-mechanical-resonator array.

Radiofrequency-enhanced vascular gene transduction and expression for intravascular MR imaging-guided therapy: feasibility study in pigs.

PubMed

Du, Xiangying; Qiu, Bensheng; Zhan, Xiangcan; Kolmakova, Antonina; Gao, Fabao; Hofmann, Lawrence V; Cheng, Linzhao; Chatterjee, Subroto; Yang, Xiaoming

2005-09-01

To evaluate the feasibility of radiofrequency (RF)-enhanced vascular gene transduction and expression by using a magnetic resonance (MR) imaging-heating guidewire as an intravascular heating vehicle during MR imaging-guided therapy. The institutional committee for animal care and use approved the experimental protocol. The study included in vitro evaluation of the use of RF energy to enhance gene transduction and expression in vascular cells, as well as in vivo validation of the feasibility of intravascular MR imaging-guided RF-enhanced vascular gene transduction and expression in pig arteries. For in vitro experiments, approximately 10(4) vascular smooth muscle cells were seeded in each of four chambers of a cell culture plate. Next, 1 mL of a green fluorescent protein gene (gfp)-bearing lentivirus was added to each chamber. Chamber 4 was heated at approximately 41 degrees C for 15 minutes by using an MR imaging-heating guidewire connected to a custom RF generator. At day 6 after transduction, the four chambers were examined and compared at confocal microscopy to determine the efficiency of gfp transduction and expression. For the in vivo experiments, a lentivirus vector bearing a therapeutic gene, vascular endothelial growth factor 165 (VEGF-165), was transferred by using a gene delivery balloon catheter in 18 femoral-iliac arteries (nine artery pairs) in domestic pigs and Yucatan pigs with atherosclerosis. During gene infusion, one femoral-iliac artery in each pig was heated to approximately 41 degrees C with RF energy transferred via the intravascular MR imaging-heating guidewire, while the contralateral artery was not heated (control condition). At day 6, the 18 arteries were harvested for quantitative Western blot analysis to compare VEGF-165 transduction and expression efficiency between RF-heated and nonheated arterial groups. Confocal microscopy showed gfp expression in chamber 4 that was 293% the level of expression in chamber 1 (49.6% +/- 25.8 vs 16

Postentry processing of recombinant adeno-associated virus type 1 and transduction of the ferret lung are altered by a factor in airway secretions.

PubMed

Yan, Ziying; Sun, Xingshen; Evans, Idil A; Tyler, Scott R; Song, Yi; Liu, Xiaoming; Sui, Hongshu; Engelhardt, John F

2013-09-01

We recently created a cystic fibrosis ferret model that acquires neonatal lung infection. To develop lung gene therapies for this model, we evaluated recombinant adeno-associated virus (rAAV)-mediated gene transfer to the neonatal ferret lung. Unlike in vitro ferret airway epithelial (FAE) cells, in vivo infection of the ferret lung with rAAV1 required proteasome inhibitors to achieve efficient airway transduction. We hypothesized that differences in transduction between these two systems were because of an in vivo secreted factor that alter the transduction biology of rAAV1. Indeed, treatment of rAAV1 with ferret airway secretory fluid (ASF) strongly inhibited rAAV1, but not rAAV2, transduction of primary FAE and HeLa cells. Properties of the ASF inhibitory factor included a strong affinity for the AAV1 capsid, heat-stability, negative charge, and sensitivity to endoproteinase Glu-C. ASF-treated rAAV1 dramatically inhibited apical transduction of FAE ALI cultures (512-fold), while only reducing viral entry by 55-fold, suggesting that postentry processing of virus was influenced by the inhibitor factor. Proteasome inhibitors rescued transduction in the presence of ASF (~1600-fold) without effecting virus internalization, while proteasome inhibitors only enhanced transduction 45-fold in the absence of ASF. These findings demonstrate that a factor in lung secretions can influence intracellular processing of rAAV1 in a proteasome-dependent fashion.

Impact of the Central Polypurine Tract on the Kinetics of Human Immunodeficiency Virus Type 1 Vector Transduction

PubMed Central

Van Maele, Bénédicte; De Rijck, Jan; De Clercq, Erik; Debyser, Zeger

2003-01-01

Lentiviral vectors derived from human immunodeficiency virus type 1 (HIV-1) show great promise as gene carriers for future gene therapy. Insertion of a fragment containing the central polypurine tract (cPPT) in HIV-1 vector constructs is known to enhance transduction efficiency drastically, reportedly by facilitating the nuclear import of HIV-1 cDNA through a central DNA flap. We have studied the impact of the cPPT on the kinetics of HIV-1 vector transduction by real-time PCR. The kinetics of total HIV-1 DNA, two-long-terminal-repeat (2-LTR) circles, and, by an Alu-PCR, integrated proviral DNA were monitored. About 6 to 12 h after transduction, the total HIV-1 DNA reached a maximum level, followed by a steep decrease. The 2-LTR circles peaked after 24 to 48 h and were diluted upon cell division. Integration of HIV-1 DNA was first detected at 12 h postinfection. When HIV-1 vectors that contained the cPPT were used, DNA synthesis was similar but a threefold higher amount of 2-LTR circles was detected, confirming the impact on nuclear import. Moreover, a 10-fold increase in the amount of integrated DNA was observed in the presence of the cPPT. Only in the absence of the cPPT was a saturation in 2-LTR circle formation seen at a high multiplicity of infection, suggesting a role for the cPPT in overcoming a barrier to the nuclear import of HIV-1 DNA. A major effect of the central DNA flap on the juxtaposition of both LTRs is unlikely, since transduction with HIV-1 vectors containing ectopic cPPT fragments resulted in increased amounts of 2-LTR circles as well as integrated DNA. Inhibitors of transduction by cPPT-containing HIV vectors were also studied by real-time PCR. The reverse transcriptase inhibitor azidothymidine (AZT) and the nonnucleoside reverse transcriptase inhibitor α-APA clearly inhibited viral DNA synthesis, whereas integrase inhibitors such as the diketo acid L-708,906 and the pyranodipyrimidine V-165 specifically inhibited integration. PMID:12663775

Improving the Transduction of Bone Marrow–Derived Cells with an Integrase-Defective Lentiviral Vector

PubMed Central

Pay, S. Louise; Qi, Xiaoping; Willard, Jeffrey F.; Godoy, Juliana; Sankhavaram, Kavya; Horton, Ranier; Mitter, Sayak K.; Quigley, Judith L.; Chang, Lung-Ji; Grant, Maria B.; Boulton, Michael E.

2018-01-01

In lentiviral vector (LV) applications where transient transgene expression is sufficient, integrase-defective lentiviral vectors (IDLVs) are beneficial for reducing the potential for off-target effects associated with insertional mutagenesis. It was previously demonstrated that human RPE65 mRNA expression from an integrating lentiviral vector (ILV) induces endogenous Rpe65 and Cralbp mRNA expression in murine bone marrow–derived cells (BMDCs), initiating programming of the cells to retinal pigment epithelium (RPE)-like cells. These cells regenerate RPE in retinal degeneration models when injected systemically. As transient expression of RPE65 is sufficient to activate endogenous RPE-associated genes for programming BMDCs, use of an ILV is an unnecessary risk. In this study, an IDLV expressing RPE65 (IDLV3-RPE65) was generated. Transduction with IDLV3-RPE65 is less efficient than the integrating vector (ILV3-RPE65). Therefore, IDLV3-RPE65 transduction was enhanced with a combination of preloading 20 × -concentrated viral supernatant on RetroNectin at a multiplicity of infection of 50 and transduction of BMDCs by low-speed centrifugation. RPE65 mRNA levels increased from ∼12-fold to ∼25-fold (p < 0.05) after modification of the IDLV3-RPE65 transduction protocol, achieving expression similar to the ∼27-fold (p < 0.05) increase observed with ILV3-RPE65. Additionally, the study shows that the same preparation of RetroNectin can be used to coat up to three wells with no reduction in transduction. Critically, IDLV3-RPE65 transduction initiates endogenous Rpe65 mRNA expression in murine BMDCs and Cralbp/CRALBP mRNA in both murine and human BMDCs, similar to expression observed in ILV3-RPE65-transduced cells. Systemic administration of ILV3-RPE65 or IDLV3-RPE65 programmed BMDCs in a mouse model of retinal degeneration is sufficient to retain visual function and reduce retinal degeneration compared to mice receiving no treatment or naïve BMDC. It is

Generation of Human Adult Mesenchymal Stromal/Stem Cells Expressing Defined Xenogenic Vascular Endothelial Growth Factor Levels by Optimized Transduction and Flow Cytometry Purification

PubMed Central

Helmrich, Uta; Marsano, Anna; Melly, Ludovic; Wolff, Thomas; Christ, Liliane; Heberer, Michael; Scherberich, Arnaud; Martin, Ivan

2012-01-01

Adult mesenchymal stromal/stem cells (MSCs) are a valuable source of multipotent progenitors for tissue engineering and regenerative medicine, but may require to be genetically modified to widen their efficacy in therapeutic applications. For example, overexpression of the angiogenic factor vascular endothelial growth factor (VEGF) at controlled levels is an attractive strategy to overcome the crucial bottleneck of graft vascularization and to avoid aberrant vascular growth. Since the regenerative potential of MSCs is rapidly lost during in vitro expansion, we sought to develop an optimized technique to achieve high-efficiency retroviral vector transduction of MSCs derived from both adipose tissue (adipose stromal cells, ASCs) or bone marrow (BMSCs) and rapidly select cells expressing desired levels of VEGF with minimal in vitro expansion. The proliferative peak of freshly isolated human ASCs and BMSCs was reached 4 and 6 days after plating, respectively. By performing retroviral vector transduction at this time point, >90% efficiency was routinely achieved before the first passage. MSCs were transduced with vectors expressing rat VEGF164 quantitatively linked to a syngenic cell surface marker (truncated rat CD8). Retroviral transduction and VEGF expression did not affect MSC phenotype nor impair their in vitro proliferation and differentiation potential. Transgene expression was also maintained during in vitro differentiation. Furthermore, three subpopulations of transduced BMSCs homogeneously producing specific low, medium, and high VEGF doses could be prospectively isolated by flow cytometry based on the intensity of their CD8 expression already at the first passage. In conclusion, this optimized platform allowed the generation of populations of genetically modified MSCs, expressing specific levels of a therapeutic transgene, already at the first passage, thereby minimizing in vitro expansion and loss of regenerative potential. PMID:22070632

Restoring functional neurofibromin by protein transduction.

PubMed

Mellert, K; Lechner, S; Lüdeke, M; Lamla, M; Möller, P; Kemkemer, R; Scheffzek, K; Kaufmann, D

2018-04-18

In Neurofibromatosis 1 (NF1) germ line loss of function mutations result in reduction of cellular neurofibromin content (NF1+/-, NF1 haploinsufficiency). The Ras-GAP neurofibromin is a very large cytoplasmic protein (2818 AA, 319 kDa) involved in the RAS-MAPK pathway. Aside from regulation of proliferation, it is involved in mechanosensoric of cells. We investigated neurofibromin replacement in cultured human fibroblasts showing reduced amount of neurofibromin. Full length neurofibromin was produced recombinantly in insect cells and purified. Protein transduction into cultured fibroblasts was performed employing cell penetrating peptides along with photochemical internalization. This combination of transduction strategies ensures the intracellular uptake and the translocation to the cytoplasm of neurofibromin. The transduced neurofibromin is functional, indicated by functional rescue of reduced mechanosensoric blindness and reduced RasGAP activity in cultured fibroblasts of NF1 patients or normal fibroblasts treated by NF1 siRNA. Our study shows that recombinant neurofibromin is able to revert cellular effects of NF1 haploinsuffiency in vitro, indicating a use of protein transduction into cells as a potential treatment strategy for the monogenic disease NF1.

Membrane guanylate cyclase, a multimodal transduction machine: history, present, and future directions

PubMed Central

Sharma, Rameshwar K.; Duda, Teresa

2014-01-01

A sequel to these authors' earlier comprehensive reviews which covered the field of mammalian membrane guanylate cyclase (MGC) from its origin to the year 2010, this article contains 13 sections. The first is historical and covers MGC from the year 1963–1987, summarizing its colorful developmental stages from its passionate pursuit to its consolidation. The second deals with the establishment of its biochemical identity. MGC becomes the transducer of a hormonal signal and founder of the peptide hormone receptor family, and creates the notion that hormone signal transduction is its sole physiological function. The third defines its expansion. The discovery of ROS-GC subfamily is made and it links ROS-GC with the physiology of phototransduction. Sections ROS-GC, a Ca2+-Modulated Two Component Transduction System to Migration Patterns and Translations of the GCAP Signals Into Production of Cyclic GMP are Different cover its biochemistry and physiology. The noteworthy events are that augmented by GCAPs, ROS-GC proves to be a transducer of the free Ca2+ signals generated within neurons; ROS-GC becomes a two-component transduction system and establishes itself as a source of cyclic GMP, the second messenger of phototransduction. Section ROS-GC1 Gene Linked Retinal Dystrophies demonstrates how this knowledge begins to be translated into the diagnosis and providing the molecular definition of retinal dystrophies. Section Controlled By Low and High Levels of [Ca2+]i, ROS-GC1 is a Bimodal Transduction Switch discusses a striking property of ROS-GC where it becomes a “[Ca2+]i bimodal switch” and transcends its signaling role in other neural processes. In this course, discovery of the first CD-GCAP (Ca2+-dependent guanylate cyclase activator), the S100B protein, is made. It extends the role of the ROS-GC transduction system beyond the phototransduction to the signaling processes in the synapse region between photoreceptor and cone ON-bipolar cells; in section Ca2

Application of Petri net based analysis techniques to signal transduction pathways.

PubMed

Sackmann, Andrea; Heiner, Monika; Koch, Ina

2006-11-02

Signal transduction pathways are usually modelled using classical quantitative methods, which are based on ordinary differential equations (ODEs). However, some difficulties are inherent in this approach. On the one hand, the kinetic parameters involved are often unknown and have to be estimated. With increasing size and complexity of signal transduction pathways, the estimation of missing kinetic data is not possible. On the other hand, ODEs based models do not support any explicit insights into possible (signal-) flows within the network. Moreover, a huge amount of qualitative data is available due to high-throughput techniques. In order to get information on the systems behaviour, qualitative analysis techniques have been developed. Applications of the known qualitative analysis methods concern mainly metabolic networks. Petri net theory provides a variety of established analysis techniques, which are also applicable to signal transduction models. In this context special properties have to be considered and new dedicated techniques have to be designed. We apply Petri net theory to model and analyse signal transduction pathways first qualitatively before continuing with quantitative analyses. This paper demonstrates how to build systematically a discrete model, which reflects provably the qualitative biological behaviour without any knowledge of kinetic parameters. The mating pheromone response pathway in Saccharomyces cerevisiae serves as case study. We propose an approach for model validation of signal transduction pathways based on the network structure only. For this purpose, we introduce the new notion of feasible t-invariants, which represent minimal self-contained subnets being active under a given input situation. Each of these subnets stands for a signal flow in the system. We define maximal common transition sets (MCT-sets), which can be used for t-invariant examination and net decomposition into smallest biologically meaningful functional units. The

Transduction of ferret airway epithelia using a pre-treatment and lentiviral gene vector.

PubMed

Cmielewski, Patricia; Farrow, Nigel; Donnelley, Martin; McIntyre, Chantelle; Penny-Dimri, Jahan; Kuchel, Tim; Parsons, David

2014-11-21

The safety and efficiency of gene therapies for cystic fibrosis (CF) need to be assessed in pre-clinical models. Using the normal ferret, this study sought to determine whether ferret airway epithelia could be transduced with a lysophosphatidylcholine (LPC) pre-treatment followed by a VSV-G pseudotyped HIV-1 based lentiviral (LV) vector, in preparation for future studies in CF ferrets. Six normal ferrets (7 -8 weeks old) were treated with a 150 μL LPC pre-treatment, followed one hour later by a 500 μL LV vector dose containing the LacZ transgene. LacZ gene expression in the conducting airways and lung was assessed by X-gal staining after 7 days. The presence of transduction in the lung, as well as off-target transduction in the liver, spleen and gonads, were assessed by qPCR. The levels of LV vector p24 protein bio-distribution in blood sera were assessed by ELISA at 0, 1, 3, 5 and 7 days. The dosing protocol was well tolerated. LacZ gene expression was observed en face in the trachea of all animals. Histology showed that ciliated and basal cells were transduced in the trachea, with rare LacZ transduced single cells noted in lung. p24 levels was not detectable in the sera of 5 of the 6 animals. The LacZ gene was not detected in the lung tissue and no off-target transduction was detected by qPCR. This study shows that ferret airway epithelia are transducible using our unique two-step pre-treatment and LV vector dosing protocol. We have identified a number of unusual anatomical factors that are likely to influence the level of transduction that can be achieved in ferret airways. The ability to transduce ferret airway epithelium is a promising step towards therapeutic LV-CFTR testing in a CF ferret model.

Postentry Processing of Recombinant Adeno-Associated Virus Type 1 and Transduction of the Ferret Lung Are Altered by a Factor in Airway Secretions

PubMed Central

Yan, Ziying; Sun, Xingshen; Evans, Idil A.; Tyler, Scott R.; Song, Yi; Liu, Xiaoming; Sui, Hongshu

2013-01-01

Abstract We recently created a cystic fibrosis ferret model that acquires neonatal lung infection. To develop lung gene therapies for this model, we evaluated recombinant adeno-associated virus (rAAV)-mediated gene transfer to the neonatal ferret lung. Unlike in vitro ferret airway epithelial (FAE) cells, in vivo infection of the ferret lung with rAAV1 required proteasome inhibitors to achieve efficient airway transduction. We hypothesized that differences in transduction between these two systems were because of an in vivo secreted factor that alter the transduction biology of rAAV1. Indeed, treatment of rAAV1 with ferret airway secretory fluid (ASF) strongly inhibited rAAV1, but not rAAV2, transduction of primary FAE and HeLa cells. Properties of the ASF inhibitory factor included a strong affinity for the AAV1 capsid, heat-stability, negative charge, and sensitivity to endoproteinase Glu-C. ASF-treated rAAV1 dramatically inhibited apical transduction of FAE ALI cultures (512-fold), while only reducing viral entry by 55-fold, suggesting that postentry processing of virus was influenced by the inhibitor factor. Proteasome inhibitors rescued transduction in the presence of ASF (∼1600-fold) without effecting virus internalization, while proteasome inhibitors only enhanced transduction 45-fold in the absence of ASF. These findings demonstrate that a factor in lung secretions can influence intracellular processing of rAAV1 in a proteasome-dependent fashion. PMID:23948055

Reversible mechanosensitive ion pumping as a part of mechanoelectrical transduction.

PubMed Central

Markin, V. S.; Tsong, T. Y.

1991-01-01

To explain the ability of some mechanosensitive cells to reverse the process of mechanotransduction and to generate mechanical oscillations and emit sound, a piezo-conformational coupling model (PCC model) is proposed. The model includes a transport protein which changes either its volume (PV-coupling) or its area in the membrane (gamma A-coupling) when undergoing conformational transitions. Such a protein can interact with an oscillating pressure to pump ions and create a transmembrane gradient if the affinities of the protein for ions are different at the two sides of membrane. The frequency and concentration windows for mechanical energy transduction were determined. Under optimal conditions, the efficiency of energy transduction can approach the theoretical maximum of 100%. If the concentration gradient exceeds the static head value (quasi-equilibrium which can be built up and maintained by this transport system), the energy transduction reverses and the transporter becomes a generator of mechanical oscillations at the expense of a concentration gradient. Estimation of thermodynamic parameters of the pump shows that the PV-coupling model would require large pressure oscillations to work while the gamma A-coupling model could work in physiological conditions. The gamma A-coupling mechanism may be used by cells for two purposes. In the reverse mode, it can be a force generator for various applications. In the direct mode, it may serve bioenergetic purposes by harvesting the energy of mechanical oscillations and storing it in the form of a concentration gradient. This pump has an unusual thermodynamic feature: it can distinguish the two components of the electrochemical potential gradient,i.e., the concentration gradient and the electrical potential, the latter serving as a permissive switch to open, or close, the pump when the potential reaches the threshold value.Predictions of the PCC model and its probable involvement in biological mechanotransduction are

Signal transduction networks and the biology of plant cells.

PubMed

Chrispeels, M J; Holuigue, L; Latorre, R; Luan, S; Orellana, A; Peña-Cortes, H; Raikhel, N V; Ronald, P C; Trewavas, A

1999-01-01

The development of plant transformation in the mid-1980s and of many new tools for cell biology, molecular genetics, and biochemistry has resulted in enormous progress in plant biology in the past decade. With the completion of the genome sequence of Arabidopsis thaliana just around the corner, we can expect even faster progress in the next decade. The interface between cell biology and signal transduction is emerging as a new and important field of research. In the past we thought of cell biology strictly in terms of organelles and their biogenesis and function, and researchers focused on questions such as, how do proteins enter chloroplasts? or, what is the structure of the macromolecules of the cell wall and how are these molecules secreted? Signal transduction dealt primarily with the perception of light (photomorphogenesis) or hormones and with the effect such signals have on enhancing the activity of specific genes. Now we see that the fields of cell biology and signal transduction are merging because signals pass between organelles and a single signal transduction pathway usually involves multiple organelles or cellular structures. Here are some examples to illustrate this new paradigm. How does abscisic acid (ABA) regulate stomatal closure? This pathway involves not only ABA receptors whose location is not yet known, but cation and anion channels in the plasma membrane, changes in the cytoskeleton, movement of water through water channels in the tonoplast and the plasma membrane, proteins with a farnesyl tail that can be located either in the cytosol or attached to a membrane, and probably unidentified ion channels in the tonoplast. In addition there are highly localized calcium oscillations in the cytoplasm resulting from the release of calcium stored in various compartments. The activities of all these cellular structures need to be coordinated during ABA-induced stomatal closure. For another example of the interplay between the proteins of signal

Disruption of Microtubules Post-Virus Entry Enhances Adeno-Associated Virus Vector Transduction

PubMed Central

Xiao, Ping-Jie; Mitchell, Angela M.; Huang, Lu; Li, Chengwen; Samulski, R. Jude

2016-01-01

Perinuclear retention of viral particles is a poorly understood phenomenon observed during many virus infections. In this study, we investigated whether perinuclear accumulation acts as a barrier to limit recombinant adeno-associated virus (rAAV) transduction. After nocodazole treatment to disrupt microtubules at microtubule-organization center (MT-MTOC) after virus entry, we observed higher rAAV transduction. To elucidate the role of MT-MTOC in rAAV infection and study its underlying mechanisms, we demonstrated that rAAV's perinuclear localization was retained by MT-MTOC with fluorescent analysis, and enhanced rAAV transduction from MT-MTOC disruption was dependent on the rAAV capsid's nuclear import signals. Interestingly, after knocking down RhoA or inhibiting its downstream effectors (ROCK and Actin), MT-MTOC disruption failed to increase rAAV transduction or nuclear entry. These data suggest that enhancement of rAAV transduction is the result of increased trafficking to the nucleus via the RhoA-ROCK-Actin pathway. Ten-fold higher rAAV transduction was also observed by disrupting MT-MTOC in brain, liver, and tumor in vivo. In summary, this study indicates that virus perinuclear accumulation at MT-MTOC is a barrier-limiting parameter for effective rAAV transduction and defines a novel defense mechanism by which host cells restrain viral invasion. PMID:26942476

The effect of the inner-hair-cell mediated transduction on the shape of neural tuning curves

NASA Astrophysics Data System (ADS)

Altoè, Alessandro; Pulkki, Ville; Verhulst, Sarah

2018-05-01

The inner hair cells of the mammalian cochlea transform the vibrations of their stereocilia into releases of neurotransmitter at the ribbon synapses, thereby controlling the activity of the afferent auditory fibers. The mechanical-to-neural transduction is a highly nonlinear process and it introduces differences between the frequency-tuning of the stereocilia and that of the afferent fibers. Using a computational model of the inner hair cell that is based on in vitro data, we estimated that smaller vibrations of the stereocilia are necessary to drive the afferent fibers above threshold at low (≤0.5 kHz) than at high (≥4 kHz) driving frequencies. In the base of the cochlea, the transduction process affects the low-frequency tails of neural tuning curves. In particular, it introduces differences between the frequency-tuning of the stereocilia and that of the auditory fibers resembling those between basilar membrane velocity and auditory fibers tuning curves in the chinchilla base. For units with a characteristic frequency between 1 and 4 kHz, the transduction process yields shallower neural than stereocilia tuning curves as the characteristic frequency decreases. This study proposes that transduction contributes to the progressive broadening of neural tuning curves from the base to the apex.

Sweet taste transduction in hamster: role of protein kinases.

PubMed

Varkevisser, B; Kinnamon, S C

2000-05-01

Two different second-messenger pathways have been implicated in sweet taste transduction: sugars produce cyclic AMP (cAMP), whereas synthetic sweeteners stimulate production of inositol 1,4, 5-tris-phosphate (IP(3)) and diacylglycerol (DAG). Both sugars and sweeteners depolarize taste cells by blocking the same resting K(+) conductance, but the intermediate steps in the transduction pathways have not been examined. In this study, the loose-patch recording technique was used to examine the role of protein kinases and other downstream regulatory proteins in the two sweet transduction pathways. Bursts of action currents were elicited from approximately 35% of fungiform taste buds in response to sucrose (200 mM) or NC-00274-01 (NC-01, 200 microM), a synthetic sweetener. To determine whether protein kinase C (PKC) plays a role in sweet transduction, taste buds were stimulated with the PKC activator PDBu (10 microM). In all sweet-responsive taste buds tested (n = 11), PDBu elicited burst of action currents. In contrast, PDBu elicited responses in only 4 of 19 sweet-unresponsive taste buds. Inhibition of PKC by bisindolylmaleimide I (0.15 microM) resulted in inhibition of the NC-01 response by approximately 75%, whereas the response to sucrose either increased or remained unchanged. These data suggest that activation of PKC is required for the transduction of synthetic sweeteners. To determine whether protein kinase A (PKA) is required for the transduction of sugars, sweet responses were examined in the presence of the membrane-permeant PKA inhibitor H-89 (10 and 19 microM). Surprisingly, H-89 did not decrease responses to either sucrose or NC-01. Instead, responses to both compounds were increased in the presence of the inhibitor. These data suggest that PKA is not required for the transduction of sugars, but may play a modulatory role in both pathways, such as adaptation of the response. We also examined whether Ca(2+)-calmodulin dependent cAMP phosphodiesterase (Ca

Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation

DTIC Science & Technology

2012-07-01

Std. Z39.18 Victoria Seewaldt, M.D. Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation Duke University Durham...attomole- zeptomole range. Internal dilution curves insure a high-dynamic calibration range. DU -26 8L DU -26 6L DU -29 5R DU -22 9.2 L DU...3: Nanobiosensor technology is translated to test for pathway deregulation in RPFNA cytology obtained from 10 high-risk women with cytological

Signal transduction and amplification through enzyme-triggered ligand release and accelerated catalysis.

PubMed

Goggins, Sean; Marsh, Barrie J; Lubben, Anneke T; Frost, Christopher G

2015-08-01

Signal transduction and signal amplification are both important mechanisms used within biological signalling pathways. Inspired by this process, we have developed a signal amplification methodology that utilises the selectivity and high activity of enzymes in combination with the robustness and generality of an organometallic catalyst, achieving a hybrid biological and synthetic catalyst cascade. A proligand enzyme substrate was designed to selectively self-immolate in the presence of the enzyme to release a ligand that can bind to a metal pre-catalyst and accelerate the rate of a transfer hydrogenation reaction. Enzyme-triggered catalytic signal amplification was then applied to a range of catalyst substrates demonstrating that signal amplification and signal transduction can both be achieved through this methodology.

Quantitative Biology of Exercise-Induced Signal Transduction Pathways.

PubMed

Liu, Timon Cheng-Yi; Liu, Gang; Hu, Shao-Juan; Zhu, Ling; Yang, Xiang-Bo; Zhang, Quan-Guang

2017-01-01

Exercise is essential in regulating energy metabolism. Exercise activates cellular, molecular, and biochemical pathways with regulatory roles in training response adaptation. Among them, endurance/strength training of an individual has been shown to activate its respective signal transduction pathways in skeletal muscle. This was further studied from the viewpoint of quantitative difference (QD). For the mean values, [Formula: see text], of two sets of data, their QD is defined as [Formula: see text] ([Formula: see text]). The function-specific homeostasis (FSH) of a function of a biosystem is a negative-feedback response of the biosystem to maintain the function-specific conditions inside the biosystem so that the function is perfectly performed. A function in/far from its FSH is called a normal/dysfunctional function. A cellular normal function can resist the activation of other signal transduction pathways so that there are normal function-specific signal transduction pathways which full activation maintains the normal function. An acute endurance/strength training may be dysfunctional, but its regular training may be normal. The normal endurance/strength training of an individual may resist the activation of other signal transduction pathways in skeletal muscle so that there may be normal endurance/strength training-specific signal transduction pathways (NEPs/NSPs) in skeletal muscle. The endurance/strength training may activate NSPs/NEPs, but the QD from the control is smaller than 0.80. The simultaneous activation of both NSPs and NEPs may enhance their respective activation, and the QD from the control is larger than 0.80. The low level laser irradiation pretreatment of rats may promote the activation of NSPs in endurance training skeletal muscle. There may be NEPs/NSPs in skeletal muscle trained by normal endurance/strength training.

Signal transduction networks in rheumatoid arthritis

PubMed Central

Hammaker, D; Sweeney, S; Firestein, G

2003-01-01

Signal transduction pathways regulate cellular responses to stress and play a critical role in inflammation. The complexity and specificity of signalling mechanisms represent major hurdles for developing effective, safe therapeutic interventions that target specific molecules. One approach is to dissect the pathways methodically to determine their hierarchy in various cell types and diseases. This approach contributed to the identification and prioritisation of specific kinases that regulate NF-κB and the mitogen activated protein (MAP) kinase cascade as especially attractive targets. Although significant issues remain with regard to the discovery of truly selective kinase inhibitors, the risks that accompany inhibition of fundamental signal transduction mechanisms can potentially be decreased by careful dissection of the pathways and rational target selection. PMID:14532158

Development of automated high throughput single molecular microfluidic detection platform for signal transduction analysis

NASA Astrophysics Data System (ADS)

Huang, Po-Jung; Baghbani Kordmahale, Sina; Chou, Chao-Kai; Yamaguchi, Hirohito; Hung, Mien-Chie; Kameoka, Jun

2016-03-01

Signal transductions including multiple protein post-translational modifications (PTM), protein-protein interactions (PPI), and protein-nucleic acid interaction (PNI) play critical roles for cell proliferation and differentiation that are directly related to the cancer biology. Traditional methods, like mass spectrometry, immunoprecipitation, fluorescence resonance energy transfer, and fluorescence correlation spectroscopy require a large amount of sample and long processing time. "microchannel for multiple-parameter analysis of proteins in single-complex (mMAPS)"we proposed can reduce the process time and sample volume because this system is composed by microfluidic channels, fluorescence microscopy, and computerized data analysis. In this paper, we will present an automated mMAPS including integrated microfluidic device, automated stage and electrical relay for high-throughput clinical screening. Based on this result, we estimated that this automated detection system will be able to screen approximately 150 patient samples in a 24-hour period, providing a practical application to analyze tissue samples in a clinical setting.

Application of Petri net based analysis techniques to signal transduction pathways

PubMed Central

Sackmann, Andrea; Heiner, Monika; Koch, Ina

2006-01-01

Background Signal transduction pathways are usually modelled using classical quantitative methods, which are based on ordinary differential equations (ODEs). However, some difficulties are inherent in this approach. On the one hand, the kinetic parameters involved are often unknown and have to be estimated. With increasing size and complexity of signal transduction pathways, the estimation of missing kinetic data is not possible. On the other hand, ODEs based models do not support any explicit insights into possible (signal-) flows within the network. Moreover, a huge amount of qualitative data is available due to high-throughput techniques. In order to get information on the systems behaviour, qualitative analysis techniques have been developed. Applications of the known qualitative analysis methods concern mainly metabolic networks. Petri net theory provides a variety of established analysis techniques, which are also applicable to signal transduction models. In this context special properties have to be considered and new dedicated techniques have to be designed. Methods We apply Petri net theory to model and analyse signal transduction pathways first qualitatively before continuing with quantitative analyses. This paper demonstrates how to build systematically a discrete model, which reflects provably the qualitative biological behaviour without any knowledge of kinetic parameters. The mating pheromone response pathway in Saccharomyces cerevisiae serves as case study. Results We propose an approach for model validation of signal transduction pathways based on the network structure only. For this purpose, we introduce the new notion of feasible t-invariants, which represent minimal self-contained subnets being active under a given input situation. Each of these subnets stands for a signal flow in the system. We define maximal common transition sets (MCT-sets), which can be used for t-invariant examination and net decomposition into smallest biologically

Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, Anna W.; Satyshur, Kenneth A.; Moreno Morales, Neydis

2016-02-01

ABSTRACT Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacteriumRamlibacter tataouinensis. RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, theR. tataouinensisbacteriophytochrome response regulatormore » (RtBRR), and a homolog, AtBRR fromAgrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRR mon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems. IMPORTANCEBphP histidine kinases and their cognate response regulators comprise widespread red light-sensing two-component systems. Much work on BphPs has focused on structural understanding of light sensing and on enhancing the natural infrared fluorescence of

Protein phosphorylation and its role in archaeal signal transduction

PubMed Central

Esser, Dominik; Hoffmann, Lena; Pham, Trong Khoa; Bräsen, Christopher; Qiu, Wen; Wright, Phillip C.; Albers, Sonja-Verena; Siebers, Bettina

2016-01-01

Reversible protein phosphorylation is the main mechanism of signal transduction that enables cells to rapidly respond to environmental changes by controlling the functional properties of proteins in response to external stimuli. However, whereas signal transduction is well studied in Eukaryotes and Bacteria, the knowledge in Archaea is still rather scarce. Archaea are special with regard to protein phosphorylation, due to the fact that the two best studied phyla, the Euryarchaeota and Crenarchaeaota, seem to exhibit fundamental differences in regulatory systems. Euryarchaeota (e.g. halophiles, methanogens, thermophiles), like Bacteria and Eukaryotes, rely on bacterial-type two-component signal transduction systems (phosphorylation on His and Asp), as well as on the protein phosphorylation on Ser, Thr and Tyr by Hanks-type protein kinases. Instead, Crenarchaeota (e.g. acidophiles and (hyper)thermophiles) only depend on Hanks-type protein phosphorylation. In this review, the current knowledge of reversible protein phosphorylation in Archaea is presented. It combines results from identified phosphoproteins, biochemical characterization of protein kinases and protein phosphatases as well as target enzymes and first insights into archaeal signal transduction by biochemical, genetic and polyomic studies. PMID:27476079

Human Bocavirus Type-1 Capsid Facilitates the Transduction of Ferret Airways by Adeno-Associated Virus Genomes.

PubMed

Yan, Ziying; Feng, Zehua; Sun, Xingshen; Zhang, Yulong; Zou, Wei; Wang, Zekun; Jensen-Cody, Chandler; Liang, Bo; Park, Soo-Yeun; Qiu, Jianming; Engelhardt, John F

2017-08-01

Human bocavirus type-1 (HBoV1) has a high tropism for the apical membrane of human airway epithelia. The packaging of a recombinant adeno-associated virus 2 (rAAV2) genome into HBoV1 capsid produces a chimeric vector (rAAV2/HBoV1) that also efficiently transduces human airway epithelia. As such, this vector is attractive for use in gene therapies to treat lung diseases such as cystic fibrosis. However, preclinical development of rAAV2/HBoV1 vectors has been hindered by the fact that humans are the only known host for HBoV1 infection. This study reports that rAAV2/HBoV1 vector is capable of efficiently transducing the lungs of both newborn (3- to 7-day-old) and juvenile (29-day-old) ferrets, predominantly in the distal airways. Analyses of in vivo, ex vivo, and in vitro models of the ferret proximal airway demonstrate that infection of this particular region is less effective than it is in humans. Studies of vector binding and endocytosis in polarized ferret proximal airway epithelial cultures revealed that a lack of effective vector endocytosis is the main cause of inefficient transduction in vitro. While transgene expression declined proportionally with growth of the ferrets following infection at 7 days of age, reinfection of ferrets with rAAV2/HBoV1 at 29 days gave rise to approximately 5-fold higher levels of transduction than observed in naive infected 29-day-old animals. The findings presented here lay the foundation for clinical development of HBoV1 capsid-based vectors for lung gene therapy in cystic fibrosis using ferret models.

Sensory Transduction in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Brown, Austin L.; Ramot, Daniel; Goodman, Miriam B.

The roundworm Caenorhabditis elegans has a well-defined and comparatively simple repertoire of sensory-guided behaviors, all of which rely on its ability to detect chemical, mechanical or thermal stimuli. In this chapter, we review what is known about the ion channels that mediate sensation in this remarkable model organism. Genetic screens for mutants defective in sensory-guided behaviors have identified genes encoding channel proteins, which are likely transducers of chemical, thermal, and mechanical stimuli. Such classical genetic approaches are now being coupled with molecular genetics and in vivo cellular physiology to elucidate how these channels are activated in specific sensory neurons. The ion channel superfamilies implicated in sensory transduction in C. elegans - CNG, TRP, and DEG/ENaC - are conserved across phyla and also appear to contribute to sensory transduction in other organisms, including vertebrates. What we learn about the role of these ion channels in C. elegans sensation is likely to illuminate analogous processes in other animals, including humans.

Efficient expansion of human keratinocyte stem/progenitor cells carrying a transgene with lentiviral vector

PubMed Central

2013-01-01

Introduction The development of an appropriate procedure for lentiviral gene transduction into keratinocyte stem cells is crucial for stem cell biology and regenerative medicine for genetic disorders of the skin. However, there is little information available on the efficiency of lentiviral transduction into human keratinocyte stem/progenitor cells and the effects of gene transduction procedures on growth potential of the stem cells by systematic assessment. Methods In this study, we explored the conditions for efficient expansion of human keratinocyte stem/progenitor cells carrying a transgene with a lentiviral vector, by using the culture of keratinocytes on a feeder layer of 3 T3 mouse fibroblasts. The gene transduction and expansion of keratinocytes carrying a transgene were analyzed by Western blotting, quantitative PCR, and flow cytometry. Results Polybrene (hexadiamine bromide) markedly enhanced the efficiency of lentiviral gene transduction, but negatively affected the maintenance of the keratinocyte stem/progenitor cells at a concentration higher than 5 μg/ml. Rho-assiciated kinase (ROCK) inhibitor Y-27632, a small molecule which enhanced keratinocyte proliferation, significantly interfered with the lentiviral transduction into cultured human keratinocytes. However, a suitable combination of polybrene and Y-27632 effectively expanded keratinocytes carrying a transgene. Conclusions This study provides information for effective expansion of cultured human keratinocyte stem/progenitor cells carrying a transgene. This point is particularly significant for the application of genetically modified keratinocyte stem/progenitor stem cells in regenerative medicine. PMID:24406242

EDITORIAL: Special section on signal transduction Special section on signal transduction

NASA Astrophysics Data System (ADS)

Shvartsman, Stanislav

2012-08-01

This special section of Physical Biology focuses on multiple aspects of signal transduction, broadly defined as the study of the mechanisms by which cells communicate with their environment. Mechanisms of cell communication involve detection of incoming signals, which can be chemical, mechanical or electromagnetic, relaying these signals to intracellular processes, such as cytoskeletal networks or gene expression systems, and, ultimately, converting these signals to responses such as cell differentiation or death. Given the multiscale nature of signal transduction systems, they must be studied at multiple levels, from the identities and structures of molecules comprising signal detection and interpretation networks, to the systems-level properties of these networks. The 11 papers in this special section illustrate some of the most exciting aspects of signal transduction research. The first two papers, by Marie-Anne Félix [1] and by Efrat Oron and Natalia Ivanova [2], focus on cell-cell interactions in developing tissues, using vulval patterning in worm and cell fate specification in mammalian embryos as prime examples of emergent cell behaviors. Next come two papers from the groups of Julio Saez-Rodriguez [3] and Kevin Janes [4]. These papers discuss how the causal relationships between multiple components of signaling systems can be inferred using multivariable statistical analysis of empirical data. An authoritative review by Zarnitsyna and Zhu [5] presents a detailed discussion of the sequence of signaling events involved in T-cell triggering. Once the structure and components of the signaling systems are determined, they can be modeled using approaches that have been successful in other physical sciences. As two examples of such approaches, reviews by Rubinstein [6] and Kholodenko [7], present reaction-diffusion models of cell polarization and thermodynamics-based models of gene regulation. An important class of models takes the form of enzymatic networks

Effects of protein transduction domain (PTD) selection and position for improved intracellular delivery of PTD-Hsp27 fusion protein formulations.

PubMed

Ul Ain, Qurrat; Lee, Jong Hwan; Woo, Young Sun; Kim, Yong-Hee

2016-09-01

Protein drugs have attracted considerable attention as therapeutic agents due to their diversity and biocompatibility. However, hydrophilic proteins possess difficulty in penetrating lipophilic cell membrane. Although protein transduction domains (PTDs) have shown effectiveness in protein delivery, the importance of selection and position of PTDs in recombinant protein vector constructs has not been investigated. This study intends to investigate the significance of PTD selection and position for therapeutic protein delivery. Heat shock protein 27 (Hsp27) would be a therapeutic protein for the treatment of ischemic heart diseases, but itself is insufficient to prevent systemic degradation and overcoming biochemical barriers during cellular transport. Among all PTD-Hsp27 fusion proteins we cloned, Tat-Hsp27 fusion protein showed the highest efficacy. Nona-arginine (9R) conjugation to the N-terminal of Hsp27 (Hsp27-T) showed higher efficacy than C-terminal. To test the synergistic effect of two PTDs, Tat was inserted to the N-terminal of Hsp27-9R. Tat-Hsp27-9R exhibited enhanced transduction efficiency and significant improvement against oxidative stress and apoptosis. PTD-Hsp27 fusion proteins have strong potential to be developed as therapeutic proteins for the treatment of ischemic heart diseases and selection and position of PTDs for improved efficacy of PTD-fusion proteins need to be optimized considering protein's nature, transduction efficiency and stability.

Report of an Army Workshop on Convergence Forecasting: Mechanochemical Transduction

DTIC Science & Technology

2012-07-01

Breakout Session 1, Group 1.........................................................................10  Figure 3. Potential Ultrasound -Mediated...Capabilities in Mechanochemical Transduction ..........10  Figure 4. Factors that Limit Potential Ultrasound -Mediated Mechanochemical Transduction... ultrasound as a mechanism to induce mechanochemical reactions. If ultrasound is to be used to provide the mechanical energy for subsequent chemical

Optical Microresonators for Sensing and Transduction: A Materials Perspective.

PubMed

Heylman, Kevin D; Knapper, Kassandra A; Horak, Erik H; Rea, Morgan T; Vanga, Sudheer K; Goldsmith, Randall H

2017-08-01

Optical microresonators confine light to a particular microscale trajectory, are exquisitely sensitive to their microenvironment, and offer convenient readout of their optical properties. Taken together, this is an immensely attractive combination that makes optical microresonators highly effective as sensors and transducers. Meanwhile, advances in material science, fabrication techniques, and photonic sensing strategies endow optical microresonators with new functionalities, unique transduction mechanisms, and in some cases, unparalleled sensitivities. In this progress report, the operating principles of these sensors are reviewed, and different methods of signal transduction are evaluated. Examples are shown of how choice of materials must be suited to the analyte, and how innovations in fabrication and sensing are coupled together in a mutually reinforcing cycle. A tremendously broad range of capabilities of microresonator sensors is described, from electric and magnetic field sensing to mechanical sensing, from single-molecule detection to imaging and spectroscopy, from operation at high vacuum to in live cells. Emerging sensing capabilities are highlighted and put into context in the field. Future directions are imagined, where the diverse capabilities laid out are combined and advances in scalability and integration are implemented, leading to the creation of a sensor unparalleled in sensitivity and information content. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Targeted Lymphoma Cell Death by Novel Signal Transduction Modifications

DTIC Science & Technology

2010-07-14

CD22 -binding peptides that initiate signal transduction and apoptosis in non-Hodgkin’s lymphoma (NHL), 2) optimize CD22 -mediated signal transduction...and lymphomacidal properties of ligand blocking anti- CD22 monoclonal antibodies (mAbs) and peptides with CD22 -specific phosphatase inhibition and 3...correlate mAb-mediated and anti- CD22 peptide-mediated in vivo physiologic changes, efficacy, and tumor targeting using advanced immuno-positron

Experimental and theoretical investigation of an impact vibration harvester with triboelectric transduction

NASA Astrophysics Data System (ADS)

Ibrahim, Alwathiqbellah; Ramini, Abdallah; Towfighian, Shahrzad

2018-03-01

There has been remarkable interest in triboelectric mechanisms because of their high efficiency, wide availability, and low-cost generation of sustainable power. Using impact vibrations, we introduce piece-wise stiffness to the system to enlarge frequency bandwidth. The triboelectric layers consist of Aluminum, which also serves as an electrode, and Polydimethylsiloxane (PDMS) with micro semi-cylindrical patterns. At the bottom of the PDMS layer, there is another Al electrode. The layers are sandwiched between the center mass of a clamped-clamped beam and its base. The center mass enhances the impact force on the triboelectric layers subjected to external vibrations. Upon impact, alternating current, caused by the contact electrification and electrostatic induction, flows between the Al electrodes. Because of the impact, the equivalent stiffness of the structure increases and as a result, the frequency bandwidth gets wider. The output voltage and power reach as large as 5.5 V, 15 μW, respectively at 0.8 g vibrational amplitude. In addition, we report how the surface charge density increases with the excitation levels. The analysis delineates the interactions between impact vibrations and triboelectric transductions. The ability of the system to achieve wider bandwidth paves the way for efficient triboelectric vibrational energy harvesters.

Transduction of Human Primitive Repopulating Hematopoietic Cells With Lentiviral Vectors Pseudotyped With Various Envelope Proteins

PubMed Central

Kim, Yoon-Sang; Wielgosz, Matthew M; Hargrove, Phillip; Kepes, Steven; Gray, John; Persons, Derek A; Nienhuis, Arthur W

2010-01-01

Lentiviral vectors are useful for transducing primitive hematopoietic cells. We examined four envelope proteins for their ability to mediate lentiviral transduction of mobilized human CD34+ peripheral blood cells. Lentiviral particles encoding green fluorescent protein (GFP) were pseudotyped with the vesicular stomatitis virus envelope glycoprotein (VSV-G), the amphotropic (AMPHO) murine leukemia virus envelope protein, the endogenous feline leukemia viral envelope protein or the feline leukemia virus type C envelope protein. Because the relative amount of genome RNA per ml was similar for each pseudotype, we transduced CD34+ cells with a fixed volume of each vector preparation. Following an overnight transduction, CD34+ cells were transplanted into immunodeficient mice which were sacrificed 12 weeks later. The average percentages of engrafted human CD45+ cells in total bone marrow were comparable to that of the control, mock-transduced group (37–45%). Lenti-particles pseudotyped with the VSV-G envelope protein transduced engrafting cells two- to tenfold better than particles pseudotyped with any of the γ-retroviral envelope proteins. There was no correlation between receptor mRNA levels for the γ-retroviral vectors and transduction efficiency of primitive hematopoietic cells. These results support the use of the VSV-G envelope protein for the development of lentiviral producer cell lines for manufacture of clinical-grade vector. PMID:20372106

Discovery of Intramolecular Signal Transduction Network Based on a New Protein Dynamics Model of Energy Dissipation

PubMed Central

Ma, Cheng-Wei; Xiu, Zhi-Long; Zeng, An-Ping

2012-01-01

A novel approach to reveal intramolecular signal transduction network is proposed in this work. To this end, a new algorithm of network construction is developed, which is based on a new protein dynamics model of energy dissipation. A key feature of this approach is that direction information is specified after inferring protein residue-residue interaction network involved in the process of signal transduction. This enables fundamental analysis of the regulation hierarchy and identification of regulation hubs of the signaling network. A well-studied allosteric enzyme, E. coli aspartokinase III, is used as a model system to demonstrate the new method. Comparison with experimental results shows that the new approach is able to predict all the sites that have been experimentally proved to desensitize allosteric regulation of the enzyme. In addition, the signal transduction network shows a clear preference for specific structural regions, secondary structural types and residue conservation. Occurrence of super-hubs in the network indicates that allosteric regulation tends to gather residues with high connection ability to collectively facilitate the signaling process. Furthermore, a new parameter of propagation coefficient is defined to determine the propagation capability of residues within a signal transduction network. In conclusion, the new approach is useful for fundamental understanding of the process of intramolecular signal transduction and thus has significant impact on rational design of novel allosteric proteins. PMID:22363664

New insights into the organization of plasma membrane and its role in signal transduction.

PubMed

Suzuki, Kenichi G N

2015-01-01

Plasma membranes have heterogeneous structures for efficient signal transduction, required to perform cell functions. Recent evidence indicates that the heterogeneous structures are produced by (1) compartmentalization by actin-based membrane skeleton, (2) raft domains, (3) receptor-receptor interactions, and (4) the binding of receptors to cytoskeletal proteins. This chapter provides an overview of recent studies on diffusion, clustering, raft association, actin binding, and signal transduction of membrane receptors, especially glycosylphosphatidylinositol (GPI)-anchored receptors. Studies on diffusion of GPI-anchored receptors suggest that rafts may be small and/or short-lived in plasma membranes. In steady state conditions, GPI-anchored receptors form transient homodimers, which may represent the "standby state" for the stable homodimers and oligomers upon ligation. Furthermore, It is proposed that upon ligation, the binding of GPI-anchored receptor clusters to cytoskeletal actin filaments produces a platform for downstream signaling, and that the pulse-like signaling easily maintains the stability of the overall signaling activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Signal Transduction in Histidine Kinases: Insights from New Structures

PubMed Central

Bhate, Manasi P.; Molnar, Kathleen S.; Goulian, Mark; DeGrado, William F.

2015-01-01

Histidine kinases (HKs) are major players in bacterial signaling. There has been an explosion of new HK crystal structures in the last five years. We globally analyze the structures of HKs to yield insights into the mechanisms by which signals are transmitted to and across protein structures in this family. We interpret known enzymological data in the context of new structural data to show how asymmetry across the dimer interface is a key feature of signal transduction in HKs, and discuss how different HK domains undergo asymmetric-to-symmetric transitions during signal transduction and catalysis. A thermodynamic framework for signaling that encompasses these various properties is presented and the consequences of weak thermodynamic coupling are discussed. The synthesis of observations from enzymology, structural biology, protein engineering and thermodynamics paves the way for a deeper molecular understanding of histidine kinase signal transduction. PMID:25982528

Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells

PubMed Central

Hindriksen, Sanne; Bramer, Arne J.; Truong, My Anh; Vromans, Martijn J. M.; Post, Jasmin B.; Verlaan-Klink, Ingrid; Snippert, Hugo J.; Lens, Susanne M. A.

2017-01-01

The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited capacity in the genetic information they can carry. Baculovirus however is capable of carrying large exogenous DNA fragments. Here we investigate the use of baculoviral vectors as a delivery vehicle for CRISPR/Cas9 based genome-editing tools. We demonstrate transduction of a panel of cell lines with Cas9 and an sgRNA sequence, which results in efficient knockout of all four targeted subunits of the chromosomal passenger complex (CPC). We further show that introduction of a homology directed repair template into the same CRISPR/Cas9 baculovirus facilitates introduction of specific point mutations and endogenous gene tags. Tagging of the CPC recruitment factor Haspin with the fluorescent reporter YFP allowed us to study its native localization as well as recruitment to the cohesin subunit Pds5B. PMID:28640891

Modeling evolution of crosstalk in noisy signal transduction networks

NASA Astrophysics Data System (ADS)

Tareen, Ammar; Wingreen, Ned S.; Mukhopadhyay, Ranjan

2018-02-01

Signal transduction networks can form highly interconnected systems within cells due to crosstalk between constituent pathways. To better understand the evolutionary design principles underlying such networks, we study the evolution of crosstalk for two parallel signaling pathways that arise via gene duplication. We use a sequence-based evolutionary algorithm and evolve the network based on two physically motivated fitness functions related to information transmission. We find that one fitness function leads to a high degree of crosstalk while the other leads to pathway specificity. Our results offer insights on the relationship between network architecture and information transmission for noisy biomolecular networks.

Efficient mRNA-Based Genetic Engineering of Human NK Cells with High-Affinity CD16 and CCR7 Augments Rituximab-Induced ADCC against Lymphoma and Targets NK Cell Migration toward the Lymph Node-Associated Chemokine CCL19.

PubMed

Carlsten, Mattias; Levy, Emily; Karambelkar, Amrita; Li, Linhong; Reger, Robert; Berg, Maria; Peshwa, Madhusudan V; Childs, Richard W

2016-01-01

For more than a decade, investigators have pursued methods to genetically engineer natural killer (NK) cells for use in clinical therapy against cancer. Despite considerable advances in viral transduction of hematopoietic stem cells and T cells, transduction efficiencies for NK cells have remained disappointingly low. Here, we show that NK cells can be genetically reprogramed efficiently using a cGMP-compliant mRNA electroporation method that induces rapid and reproducible transgene expression in nearly all transfected cells, without negatively influencing their viability, phenotype, and cytotoxic function. To study its potential therapeutic application, we used this approach to improve key aspects involved in efficient lymphoma targeting by adoptively infused ex vivo-expanded NK cells. Electroporation of NK cells with mRNA coding for the chemokine receptor CCR7 significantly promoted migration toward the lymph node-associated chemokine CCL19. Further, introduction of mRNA coding for the high-affinity antibody-binding receptor CD16 (CD16-158V) substantially augmented NK cell cytotoxicity against rituximab-coated lymphoma cells. Based on these data, we conclude that this approach can be utilized to genetically modify multiple modalities of NK cells in a highly efficient manner with the potential to improve multiple facets of their in vivo tumor targeting, thus, opening a new arena for the development of more efficacious adoptive NK cell-based cancer immunotherapies.

Potential insight for drug discovery from high fidelity receptor-mediated transduction mechanisms in insects

PubMed Central

Raffa, Robert B.; Raffa, Kenneth F.

2011-01-01

Introduction There is a pervasive and growing concern about the small number of new pharmaceutical agents. There are many proposed explanations for this trend that do not involve the drug-discovery process per se, but the discovery process itself has also come under scrutiny. If the current paradigms are indeed not working, where are novel ideas to come from? Perhaps it is time to look to novel sources. Areas covered The receptor-signaling and 2nd-messenger transduction processes present in insects are quite similar to those in mammals (involving G proteins, ion channels, etc.). However, a review of these systems reveals an unprecedented degree of high potency and receptor selectivity to an extent greater than that modeled in most current drug-discovery approaches. Expert opinion A better understanding of insect receptor pharmacology could stimulate novel theoretical and practical ideas in mammalian pharmacology (drug discovery) and, conversely, the application of pharmacology and medicinal chemistry principles could stimulate novel advances in entomology (safer and more targeted control of pest species). PMID:21984882

Olfactory transduction pathways in the Senegalese sole Solea senegalensis.

PubMed

Velez, Z; Hubbard, P C; Barata, E N; Canário, A V M

2013-09-01

This study tested whether differences in sensitivity between the upper and lower olfactory epithelia of Solea senegalensis are associated with different odorant receptors and transduction pathways, using the electro-olfactogram. Receptor mechanisms were assessed by cross-adaptation with amino acids (L-cysteine, L-phenylalanine and 1-methyl-L-tryptophan) and bile acids (taurocholic acid and cholic acid). This suggested that relatively specific receptors exist for 1-methyl-L-tryptophan and L-phenylalanine (food-related odorants) in the lower epithelium, and for taurocholic acid (conspecific-derived odorant) in the upper. Inhibition by U73122 [a phospholipase C (PLC) inhibitor] suggested that olfactory responses to amino acids were mediated mostly, but not entirely, by PLC-mediated transduction (IC50 ; 15-55 nM), whereas bile acid responses were mediated by both PLC and adenylate cyclase-cyclic adenosine monophosphate (AC-cAMP) (using SQ-22536; an AC inhibitor). Simultaneous application of both drugs rarely inhibited responses completely, suggesting possible involvement of non-PLC and non-AC mediated mechanisms. For aromatic amino acids and bile acids, there were differences in the contribution of each transduction pathway (PLC, AC and non-PLC and non-AC) between the two epithelia. These results suggest that differences in sensitivity of the two epithelia are associated with differences in odorant receptors and transduction mechanisms. © 2013 The Fisheries Society of the British Isles.

Antidepressive effects of targeting ELK-1 signal transduction.

PubMed

Apazoglou, Kallia; Farley, Séverine; Gorgievski, Victor; Belzeaux, Raoul; Lopez, Juan Pablo; Grenier, Julien; Ibrahim, El Chérif; El Khoury, Marie-Anne; Tse, Yiu C; Mongredien, Raphaele; Barbé, Alexandre; de Macedo, Carlos E A; Jaworski, Wojciech; Bochereau, Ariane; Orrico, Alejandro; Isingrini, Elsa; Guinaudie, Chloé; Mikasova, Lenka; Louis, Franck; Gautron, Sophie; Groc, Laurent; Massaad, Charbel; Yildirim, Ferah; Vialou, Vincent; Dumas, Sylvie; Marti, Fabio; Mechawar, Naguib; Morice, Elise; Wong, Tak P; Caboche, Jocelyne; Turecki, Gustavo; Giros, Bruno; Tzavara, Eleni T

2018-05-07

Depression, a devastating psychiatric disorder, is a leading cause of disability worldwide. Current antidepressants address specific symptoms of the disease, but there is vast room for improvement 1 . In this respect, new compounds that act beyond classical antidepressants to target signal transduction pathways governing synaptic plasticity and cellular resilience are highly warranted 2-4 . The extracellular signal-regulated kinase (ERK) pathway is implicated in mood regulation 5-7 , but its pleiotropic functions and lack of target specificity prohibit optimal drug development. Here, we identified the transcription factor ELK-1, an ERK downstream partner 8 , as a specific signaling module in the pathophysiology and treatment of depression that can be targeted independently of ERK. ELK1 mRNA was upregulated in postmortem hippocampal tissues from depressed suicides; in blood samples from depressed individuals, failure to reduce ELK1 expression was associated with resistance to treatment. In mice, hippocampal ELK-1 overexpression per se produced depressive behaviors; conversely, the selective inhibition of ELK-1 activation prevented depression-like molecular, plasticity and behavioral states induced by stress. Our work stresses the importance of target selectivity for a successful approach for signal-transduction-based antidepressants, singles out ELK-1 as a depression-relevant transducer downstream of ERK and brings proof-of-concept evidence for the druggability of ELK-1.

The ethylene signal transduction pathway in Arabidopsis

NASA Technical Reports Server (NTRS)

Kieber, J. J.; Evans, M. L. (Principal Investigator)

1997-01-01

The gaseous hormone ethylene is an important regulator of plant growth and development. Using a simple response of etiolated seedlings to ethylene as a genetic screen, genes involved in ethylene signal transduction have been identified in Arabidopsis. Analysis of two of these genes that have been cloned reveals that ethylene signalling involves a combination of a protein (ETR1) with similarity to bacterial histidine kinases and a protein (CTR1) with similarity to Raf-1, a protein kinase involved in multiple signalling cascades in eukaryotic cells. Several lines of investigation provide compelling evidence that ETR1 encodes an ethylene receptor. For the first time there is a glimpse of the molecular circuitry underlying the signal transduction pathway for a plant hormone.

Highly efficient gene inactivation by adenoviral CRISPR/Cas9 in human primary cells

PubMed Central

Tielen, Frans; Elstak, Edo; Benschop, Julian; Grimbergen, Max; Stallen, Jan; Janssen, Richard; van Marle, Andre; Essrich, Christian

2017-01-01

Phenotypic assays using human primary cells are highly valuable tools for target discovery and validation in drug discovery. Expression knockdown (KD) of such targets in these assays allows the investigation of their role in models of disease processes. Therefore, efficient and fast modes of protein KD in phenotypic assays are required. The CRISPR/Cas9 system has been shown to be a versatile and efficient means of gene inactivation in immortalized cell lines. Here we describe the use of adenoviral (AdV) CRISPR/Cas9 vectors for efficient gene inactivation in two human primary cell types, normal human lung fibroblasts and human bronchial epithelial cells. The effects of gene inactivation were studied in the TGF-β-induced fibroblast to myofibroblast transition assay (FMT) and the epithelial to mesenchymal transition assay (EMT), which are SMAD3 dependent and reflect pathogenic mechanisms observed in fibrosis. Co-transduction (co-TD) of AdV Cas9 with SMAD3-targeting guide RNAs (gRNAs) resulted in fast and efficient genome editing judged by insertion/deletion (indel) formation, as well as significant reduction of SMAD3 protein expression and nuclear translocation. This led to phenotypic changes downstream of SMAD3 inhibition, including substantially decreased alpha smooth muscle actin and fibronectin 1 expression, which are markers for FMT and EMT, respectively. A direct comparison between co-TD of separate Cas9 and gRNA AdV, versus TD with a single “all-in-one” Cas9/gRNA AdV, revealed that both methods achieve similar levels of indel formation. These data demonstrate that AdV CRISPR/Cas9 is a useful and efficient tool for protein KD in human primary cell phenotypic assays. The use of AdV CRISPR/Cas9 may offer significant advantages over the current existing tools and should enhance target discovery and validation opportunities. PMID:28800587

SPINDLY, a tetratricopeptide repeat protein involved in gibberellin signal transduction in Arabidopsis.

PubMed Central

Jacobsen, S E; Binkowski, K A; Olszewski, N E

1996-01-01

Gibberellins (GAs) are a major class of plant hormones that control many developmental processes, including seed development and germination, flower and fruit development, and flowering time. Genetic studies with Arabidopsis thaliana have identified two genes involved in GA perception or signal transduction. A semidominant mutation at the GIBBERELLIN INSENSITIVE (GAI) locus results in plants resembling GA-deficient mutants but exhibiting reduced sensitivity to GA. Recessive mutations at the SPINDLY (SPY) locus cause a phenotype that is consistent with constitutive activation of GA signal transduction. Here we show that a strong allele of spy is completely epistatic to gai, indicating that SPY acts downstream of GAI. We have cloned the SPY gene and shown that it encodes a new type of signal transduction protein, which contains a tetratricopeptide repeat region, likely serving as a protein interaction domain, and a novel C-terminal region. Mutations in both domains increase GA signal transduction. The presence of a similar gene in Caenorhabditis elegans suggests that SPY represents a class of signal transduction proteins that is present throughout the eukaryotes. Images Fig. 1 Fig. 2 Fig. 3 PMID:8799194

Ras-Mediated Signal Transduction and Virulence in Human Pathogenic Fungi

PubMed Central

Fortwendel, Jarrod R.

2013-01-01

Signal transduction pathways regulating growth and stress responses are areas of significant study in the effort to delineate pathogenic mechanisms of fungi. In-depth knowledge of signal transduction events deepens our understanding of how a fungal pathogen is able to sense changes in the environment and respond accordingly by modulation of gene expression and re-organization of cellular activities to optimize fitness. Members of the Ras protein family are important regulators of growth and differentiation in eukaryotic organisms, and have been the focus of numerous studies exploring fungal pathogenesis. Here, the current data regarding Ras signal transduction are reviewed for three major pathogenic fungi: Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus. Particular emphasis is placed on Ras-protein interactions during control of morphogenesis, stress response and virulence. PMID:24855584

Dynamic Receptor Team Formation Can Explain the High Signal Transduction Gain in Escherichia coli

PubMed Central

Albert, Réka; Chiu, Yu-wen; Othmer, Hans G.

2004-01-01

Evolution has provided many organisms with sophisticated sensory systems that enable them to respond to signals in their environment. The response frequently involves alteration in the pattern of movement, either by directed movement, a process called taxis, or by altering the speed or frequency of turning, which is called kinesis. Chemokinesis has been most thoroughly studied in the peritrichous bacterium Escherichia coli, which has four helical flagella distributed over the cell surface, and swims by rotating them. When rotated counterclockwise the flagella coalesce into a propulsive bundle, producing a relatively straight “run,” and when rotated clockwise they fly apart, resulting in a “tumble” which reorients the cell with little translocation. A stochastic process generates the runs and tumbles, and in a chemoeffector gradient, runs that carry the cell in a favorable direction are extended. The cell senses spatial gradients as temporal changes in receptor occupancy and changes the probability of counterclockwise rotation (the bias) on a fast timescale, but adaptation returns the bias to baseline on a slow timescale, enabling the cell to detect and respond to further concentration changes. The overall structure of the signal transduction pathways is well characterized in E. coli, but important details are still not understood. Only recently has a source of gain in the signal transduction network been identified experimentally, and here we present a mathematical model based on dynamic assembly of receptor teams that can explain this observation. PMID:15111386

Dynamic receptor team formation can explain the high signal transduction gain in Escherichia coli.

PubMed

Albert, Réka; Chiu, Yu-Wen; Othmer, Hans G

2004-05-01

Evolution has provided many organisms with sophisticated sensory systems that enable them to respond to signals in their environment. The response frequently involves alteration in the pattern of movement, either by directed movement, a process called taxis, or by altering the speed or frequency of turning, which is called kinesis. Chemokinesis has been most thoroughly studied in the peritrichous bacterium Escherichia coli, which has four helical flagella distributed over the cell surface, and swims by rotating them. When rotated counterclockwise the flagella coalesce into a propulsive bundle, producing a relatively straight "run," and when rotated clockwise they fly apart, resulting in a "tumble" which reorients the cell with little translocation. A stochastic process generates the runs and tumbles, and in a chemoeffector gradient, runs that carry the cell in a favorable direction are extended. The cell senses spatial gradients as temporal changes in receptor occupancy and changes the probability of counterclockwise rotation (the bias) on a fast timescale, but adaptation returns the bias to baseline on a slow timescale, enabling the cell to detect and respond to further concentration changes. The overall structure of the signal transduction pathways is well characterized in E. coli, but important details are still not understood. Only recently has a source of gain in the signal transduction network been identified experimentally, and here we present a mathematical model based on dynamic assembly of receptor teams that can explain this observation.

Polymerase chain reaction-based detection of myc transduction in feline leukemia virus-infected cats.

PubMed

Sumi, Ryosuke; Miyake, Ariko; Endo, Taiji; Ohsato, Yoshiharu; Ngo, Minh Ha; Nishigaki, Kazuo

2018-04-01

Feline lymphomas are associated with the transduction and activation of cellular proto-oncogenes, such as c-myc, by feline leukemia virus (FeLV). We describe a polymerase chain reaction assay for detection of myc transduction usable in clinical diagnosis. The assay targets c-myc exons 2 and 3, which together result in a FeLV-specific fusion gene following c-myc transduction. When this assay was conducted on FeLV-infected feline tissues submitted for clinical diagnosis of tumors, myc transduction was detected in 14% of T-cell lymphoma/leukemias. This newly established system could become a useful diagnostic tool in veterinary medicine.

Reduced modeling of signal transduction – a modular approach

PubMed Central

Koschorreck, Markus; Conzelmann, Holger; Ebert, Sybille; Ederer, Michael; Gilles, Ernst Dieter

2007-01-01

Background Combinatorial complexity is a challenging problem in detailed and mechanistic mathematical modeling of signal transduction. This subject has been discussed intensively and a lot of progress has been made within the last few years. A software tool (BioNetGen) was developed which allows an automatic rule-based set-up of mechanistic model equations. In many cases these models can be reduced by an exact domain-oriented lumping technique. However, the resulting models can still consist of a very large number of differential equations. Results We introduce a new reduction technique, which allows building modularized and highly reduced models. Compared to existing approaches further reduction of signal transduction networks is possible. The method also provides a new modularization criterion, which allows to dissect the model into smaller modules that are called layers and can be modeled independently. Hallmarks of the approach are conservation relations within each layer and connection of layers by signal flows instead of mass flows. The reduced model can be formulated directly without previous generation of detailed model equations. It can be understood and interpreted intuitively, as model variables are macroscopic quantities that are converted by rates following simple kinetics. The proposed technique is applicable without using complex mathematical tools and even without detailed knowledge of the mathematical background. However, we provide a detailed mathematical analysis to show performance and limitations of the method. For physiologically relevant parameter domains the transient as well as the stationary errors caused by the reduction are negligible. Conclusion The new layer based reduced modeling method allows building modularized and strongly reduced models of signal transduction networks. Reduced model equations can be directly formulated and are intuitively interpretable. Additionally, the method provides very good approximations especially for

Mitochondria-derived hydrogen peroxide selectively enhances T cell receptor-initiated signal transduction.

PubMed

Gill, Tejpal; Levine, Alan D

2013-09-06

T cell receptor (TCR)-initiated signal transduction is reported to increase production of intracellular reactive oxygen species, such as superoxide (O2˙(-)) and hydrogen peroxide (H2O2), as second messengers. Although H2O2 can modulate signal transduction by inactivating protein phosphatases, the mechanism and the subcellular localization of intracellular H2O2 as a second messenger of the TCR are not known. The antioxidant enzyme superoxide dismutase (SOD) catalyzes the dismutation of highly reactive O2˙(-) into H2O2 and thus acts as an intracellular generator of H2O2. As charged O2˙(-) is unable to diffuse through intracellular membranes, cells express distinct SOD isoforms in the cytosol (Cu,Zn-SOD) and mitochondria (Mn-SOD), where they locally scavenge O2˙(-) leading to production of H2O2. A 2-fold organelle-specific overexpression of either SOD in Jurkat T cell lines increases intracellular production of H2O2 but does not alter the levels of intracellular H2O2 scavenging enzymes such as catalase, membrane-bound peroxiredoxin1 (Prx1), and cytosolic Prx2. We report that overexpression of Mn-SOD enhances tyrosine phosphorylation of TCR-associated membrane proximal signal transduction molecules Lck, LAT, ZAP70, PLCγ1, and SLP76 within 1 min of TCR cross-linking. This increase in mitochondrial H2O2 specifically modulates MAPK signaling through the JNK/cJun pathway, whereas overexpressing Cu,Zn-SOD had no effect on any of these TCR-mediated signaling molecules. As mitochondria translocate to the immunological synapse during TCR activation, we hypothesize this translocation provides the effective concentration of H2O2 required to selectively modulate downstream signal transduction pathways.

In Vivo Stable Transduction of Humanized Liver Tissue in Chimeric Mice via High-Capacity Adenovirus–Lentivirus Hybrid Vector

PubMed Central

Kataoka, Miho; Tateno, Chise; Yoshizato, Katsutoshi; Kawasaki, Yoshiko; Kimura, Takahiro; Faure-Kumar, Emmanuelle; Palmer, Donna J.; Ng, Philip; Okamura, Haruki; Kasahara, Noriyuki

2010-01-01

Abstract We developed hybrid vectors employing high-capacity adenovirus as a first-stage carrier encoding all the components required for in situ production of a second-stage lentivirus, thereby achieving stable transgene expression in secondary target cells. Such vectors have never previously been tested in normal tissues, because of the scarcity of suitable in vivo systems permissive for second-stage lentivirus assembly. Here we employed a novel murine model in which endogenous liver tissue is extensively reconstituted with engrafted human hepatocytes, and successfully achieved stable transduction by the second-stage lentivirus produced in situ from first-stage adenovirus. This represents the first demonstration of the functionality of adenoviral-lentiviral hybrid vectors in a normal parenchymal organ in vivo. PMID:19725756

Magnetic levitation-based electromagnetic energy harvesting: a semi-analytical non-linear model for energy transduction

NASA Astrophysics Data System (ADS)

Soares Dos Santos, Marco P.; Ferreira, Jorge A. F.; Simões, José A. O.; Pascoal, Ricardo; Torrão, João; Xue, Xiaozheng; Furlani, Edward P.

2016-01-01

Magnetic levitation has been used to implement low-cost and maintenance-free electromagnetic energy harvesting. The ability of levitation-based harvesting systems to operate autonomously for long periods of time makes them well-suited for self-powering a broad range of technologies. In this paper, a combined theoretical and experimental study is presented of a harvester configuration that utilizes the motion of a levitated hard-magnetic element to generate electrical power. A semi-analytical, non-linear model is introduced that enables accurate and efficient analysis of energy transduction. The model predicts the transient and steady-state response of the harvester a function of its motion (amplitude and frequency) and load impedance. Very good agreement is obtained between simulation and experiment with energy errors lower than 14.15% (mean absolute percentage error of 6.02%) and cross-correlations higher than 86%. The model provides unique insight into fundamental mechanisms of energy transduction and enables the geometric optimization of harvesters prior to fabrication and the rational design of intelligent energy harvesters.

Magnetic levitation-based electromagnetic energy harvesting: a semi-analytical non-linear model for energy transduction

PubMed Central

Soares dos Santos, Marco P.; Ferreira, Jorge A. F.; Simões, José A. O.; Pascoal, Ricardo; Torrão, João; Xue, Xiaozheng; Furlani, Edward P.

2016-01-01

Magnetic levitation has been used to implement low-cost and maintenance-free electromagnetic energy harvesting. The ability of levitation-based harvesting systems to operate autonomously for long periods of time makes them well-suited for self-powering a broad range of technologies. In this paper, a combined theoretical and experimental study is presented of a harvester configuration that utilizes the motion of a levitated hard-magnetic element to generate electrical power. A semi-analytical, non-linear model is introduced that enables accurate and efficient analysis of energy transduction. The model predicts the transient and steady-state response of the harvester a function of its motion (amplitude and frequency) and load impedance. Very good agreement is obtained between simulation and experiment with energy errors lower than 14.15% (mean absolute percentage error of 6.02%) and cross-correlations higher than 86%. The model provides unique insight into fundamental mechanisms of energy transduction and enables the geometric optimization of harvesters prior to fabrication and the rational design of intelligent energy harvesters. PMID:26725842

From receptor binding kinetics to signal transduction; a missing link in predicting in vivo drug-action.

PubMed

Nederpelt, Indira; Kuzikov, Maria; de Witte, Wilbert E A; Schnider, Patrick; Tuijt, Bruno; Gul, Sheraz; IJzerman, Adriaan P; de Lange, Elizabeth C M; Heitman, Laura H

2017-10-26

An important question in drug discovery is how to overcome the significant challenge of high drug attrition rates due to lack of efficacy and safety. A missing link in the understanding of determinants for drug efficacy is the relation between drug-target binding kinetics and signal transduction, particularly in the physiological context of (multiple) endogenous ligands. We hypothesized that the kinetic binding parameters of both drug and endogenous ligand play a crucial role in determining cellular responses, using the NK1 receptor as a model system. We demonstrated that the binding kinetics of both antagonists (DFA and aprepitant) and endogenous agonists (NKA and SP) have significantly different effects on signal transduction profiles, i.e. potency values, in vitro efficacy values and onset rate of signal transduction. The antagonistic effects were most efficacious with slowly dissociating aprepitant and slowly associating NKA while the combination of rapidly dissociating DFA and rapidly associating SP had less significant effects on the signal transduction profiles. These results were consistent throughout different kinetic assays and cellular backgrounds. We conclude that knowledge of the relationship between in vitro drug-target binding kinetics and cellular responses is important to ultimately improve the understanding of drug efficacy in vivo.

Recombinant adeno-associated virus mediates a high level of gene transfer but less efficient integration in the K562 human hematopoietic cell line.

PubMed Central

Malik, P; McQuiston, S A; Yu, X J; Pepper, K A; Krall, W J; Podsakoff, G M; Kurtzman, G J; Kohn, D B

1997-01-01

We tested the ability of a recombinant adeno-associated virus (rAAV) vector to express and integrate exogenous DNA into human hematopoietic cells in the absence of selection. We developed an rAAV vector, AAV-tNGFR, carrying a truncated rat nerve growth factor receptor (tNGFR) cDNA as a cell surface reporter under the control of the Moloney murine leukemia virus (MoMuLV) long terminal repeat. An analogous MoMuLV-based retroviral vector (L-tNGFR) was used in parallel, and gene transfer and expression in human hematopoietic cells were assessed by flow cytometry and DNA analyses. Following gene transfer into K562 cells with AAV-tNGFR at a multiplicity of infection (MOI) of 13 infectious units (IU), 26 to 38% of cells expressed tNGFR on the surface early after transduction, but the proportion of tNGFR expressing cells steadily declined to 3.0 to 3.5% over 1 month of culture. At an MOI of 130 IU, nearly all cells expressed tNGFR immediately posttransduction, but the proportion of cells expressing tNGFR declined to 62% over 2 months of culture. The decline in the proportion of AAV-tNGFR-expressing cells was associated with ongoing losses of vector genomes. In contrast, K562 cells transduced with the retroviral vector L-tNGFR expressed tNGFR in a constant fraction. Integration analyses on clones showed that integration occurred at different sites. Integration frequencies were estimated at about 49% at an MOI of 130 and 2% at an MOI of 1.3. Transduction of primary human CD34+ progenitor cells by AAV-tNGFR was less efficient than with K562 cells and showed a declining percentage of cells expressing tNGFR over 2 weeks of culture. Thus, purified rAAV caused very high gene transfer and expression in human hematopoietic cells early after transduction, which steadily declined during cell passage in the absence of selection. Although the efficiency of integration was low, overall integration was markedly improved at a high MOI. While prolonged episomal persistence may be adequate

Recombinant adeno-associated virus mediates a high level of gene transfer but less efficient integration in the K562 human hematopoietic cell line.

PubMed

Malik, P; McQuiston, S A; Yu, X J; Pepper, K A; Krall, W J; Podsakoff, G M; Kurtzman, G J; Kohn, D B

1997-03-01

We tested the ability of a recombinant adeno-associated virus (rAAV) vector to express and integrate exogenous DNA into human hematopoietic cells in the absence of selection. We developed an rAAV vector, AAV-tNGFR, carrying a truncated rat nerve growth factor receptor (tNGFR) cDNA as a cell surface reporter under the control of the Moloney murine leukemia virus (MoMuLV) long terminal repeat. An analogous MoMuLV-based retroviral vector (L-tNGFR) was used in parallel, and gene transfer and expression in human hematopoietic cells were assessed by flow cytometry and DNA analyses. Following gene transfer into K562 cells with AAV-tNGFR at a multiplicity of infection (MOI) of 13 infectious units (IU), 26 to 38% of cells expressed tNGFR on the surface early after transduction, but the proportion of tNGFR expressing cells steadily declined to 3.0 to 3.5% over 1 month of culture. At an MOI of 130 IU, nearly all cells expressed tNGFR immediately posttransduction, but the proportion of cells expressing tNGFR declined to 62% over 2 months of culture. The decline in the proportion of AAV-tNGFR-expressing cells was associated with ongoing losses of vector genomes. In contrast, K562 cells transduced with the retroviral vector L-tNGFR expressed tNGFR in a constant fraction. Integration analyses on clones showed that integration occurred at different sites. Integration frequencies were estimated at about 49% at an MOI of 130 and 2% at an MOI of 1.3. Transduction of primary human CD34+ progenitor cells by AAV-tNGFR was less efficient than with K562 cells and showed a declining percentage of cells expressing tNGFR over 2 weeks of culture. Thus, purified rAAV caused very high gene transfer and expression in human hematopoietic cells early after transduction, which steadily declined during cell passage in the absence of selection. Although the efficiency of integration was low, overall integration was markedly improved at a high MOI. While prolonged episomal persistence may be adequate

Falsification of the ionic channel theory of hair cell transduction.

PubMed

Rossetto, Michelangelo

2013-11-01

The hair cell provides the transduction of mechanical vibrations in the balance and acoustic sense of all vertebrates that swim, walk, or fly. The current theory places hair cell transduction in a mechanically controlled ion channel. Although the theory of a mechanical input modulating the flow of ions through an ion pore has been a useful tool, it is falsified by experimental data in the literature and can be definitively falsified by a proposed experiment.

Measles virus envelope pseudotyped lentiviral vectors transduce quiescent human HSCs at an efficiency without precedent

PubMed Central

Lévy, Camille; Amirache, Fouzia; Girard-Gagnepain, Anais; Frecha, Cecilia; Roman-Rodríguez, Francisco J.; Bernadin, Ornellie; Costa, Caroline; Nègre, Didier; Gutierrez-Guerrero, Alejandra; Vranckx, Lenard S.; Clerc, Isabelle; Taylor, Naomi; Thielecke, Lars; Cornils, Kerstin; Bueren, Juan A.; Rio, Paula; Gijsbers, Rik; Cosset, François-Loïc

2017-01-01

Hematopoietic stem cell (HSC)–based gene therapy trials are now moving toward the use of lentiviral vectors (LVs) with success. However, one challenge in the field remains: efficient transduction of HSCs without compromising their stem cell potential. Here we showed that measles virus glycoprotein–displaying LVs (hemagglutinin and fusion protein LVs [H/F-LVs]) were capable of transducing 100% of early-acting cytokine-stimulated human CD34+ (hCD34+) progenitor cells upon a single application. Strikingly, these H/F-LVs also allowed transduction of up to 70% of nonstimulated quiescent hCD34+ cells, whereas conventional vesicular stomatitis virus G (VSV-G)–LVs reached 5% at the most with H/F-LV entry occurring exclusively through the CD46 complement receptor. Importantly, reconstitution of NOD/SCIDγc−/− (NSG) mice with H/F-LV transduced prestimulated or resting hCD34+ cells confirmed these high transduction levels in all myeloid and lymphoid lineages. Remarkably, for resting CD34+ cells, secondary recipients exhibited increasing transduction levels of up to 100%, emphasizing that H/F-LVs efficiently gene-marked HSCs in the resting state. Because H/F-LVs promoted ex vivo gene modification of minimally manipulated CD34+ progenitors that maintained stemness, we assessed their applicability in Fanconi anemia, a bone marrow (BM) failure with chromosomal fragility. Notably, only H/F-LVs efficiently gene-corrected minimally stimulated hCD34+ cells in unfractionated BM from these patients. These H/F-LVs improved HSC gene delivery in the absence of cytokine stimulation while maintaining their stem cell potential. Thus, H/F-LVs will facilitate future clinical applications requiring HSC gene modification, including BM failure syndromes, for which treatment has been very challenging up to now. PMID:29296856

Coupled stochastic spatial and non-spatial simulations of ErbB1 signaling pathways demonstrate the importance of spatial organization in signal transduction.

PubMed

Costa, Michelle N; Radhakrishnan, Krishnan; Wilson, Bridget S; Vlachos, Dionisios G; Edwards, Jeremy S

2009-07-23

The ErbB family of receptors activates intracellular signaling pathways that control cellular proliferation, growth, differentiation and apoptosis. Given these central roles, it is not surprising that overexpression of the ErbB receptors is often associated with carcinogenesis. Therefore, extensive laboratory studies have been devoted to understanding the signaling events associated with ErbB activation. Systems biology has contributed significantly to our current understanding of ErbB signaling networks. However, although computational models have grown in complexity over the years, little work has been done to consider the spatial-temporal dynamics of receptor interactions and to evaluate how spatial organization of membrane receptors influences signaling transduction. Herein, we explore the impact of spatial organization of the epidermal growth factor receptor (ErbB1/EGFR) on the initiation of downstream signaling. We describe the development of an algorithm that couples a spatial stochastic model of membrane receptors with a nonspatial stochastic model of the reactions and interactions in the cytosol. This novel algorithm provides a computationally efficient method to evaluate the effects of spatial heterogeneity on the coupling of receptors to cytosolic signaling partners. Mathematical models of signal transduction rarely consider the contributions of spatial organization due to high computational costs. A hybrid stochastic approach simplifies analyses of the spatio-temporal aspects of cell signaling and, as an example, demonstrates that receptor clustering contributes significantly to the efficiency of signal propagation from ligand-engaged growth factor receptors.

Physics of transduction in ionic liquid-swollen Nafion membranes

NASA Astrophysics Data System (ADS)

Bennett, Matthew; Leo, Donald

2006-03-01

Ionic polymer transducers are a class of electroactive polymers that are able to generate large strains (1-5%) in response to low voltage inputs (1-5 V). Additionally, these materials generate electrical charge in response to mechanical strain and are therefore able to operate as soft, distributed sensors. Traditionally, ionic polymer transducers have been limited in their application by their hydration dependence. This work seeks to overcome this limitation by replacing the water with an ionic liquid. Ionic liquids are molten salts that exhibit very high thermal and electrochemical stability while also possessing high ionic conductivity. Results have shown that an ionic liquid-swollen ionic polymer transducer can operate for more than 250,000 cycles in air as compared to about 2,000 cycles for a water-swollen transducer. The current work examines the mechanisms of transduction in ionic liquid-swollen transducers based on Nafion polymer membranes. Specifically, the morphology and relevant ion associations within these membranes are investigated by the use of small-angle X-ray scattering (SAXS), Fourier transform infrared spectroscopy (FTIR), and nuclear magnetic resonance spectroscopy (NMR). These results reveal that the ionic liquid interacts with the membrane in much the same way that water does, and that the counterions of the Nafion polymer are the primary charge carriers. The results of these analyses are compared to the macroscopic transduction behavior in order to develop a model of the charge transport mechanism responsible for electromechanical coupling in these membranes.

Effects of electrode surface structure on the mechanoelectrical transduction of IPMC sensors

NASA Astrophysics Data System (ADS)

Palmre, Viljar; Pugal, David; Kim, Kwang

2014-03-01

This study investigates the effects of electrode surface structure on the mechanoelectrical transduction of IPMC sensors. A physics-based mechanoelectrical transduction model was developed that takes into account the electrode surface profile (shape) by describing the polymer-electrode interface as a Koch fractal structure. Based on the model, the electrode surface effects were experimentally investigated in case of IPMCs with Pd-Pt electrodes. IPMCs with different electrode surface structures were fabricated through electroless plating process by appropriately controlling the synthesis parameters and conditions. The changes in the electrode surface morphology and the corresponding effects on the IPMC mechanoelectrical transduction were examined. Our experimental results indicate that increasing the dispersion of Pd particles near the membrane surface, and thus the polymer-electrode interfacial area, leads to a higher peak mechanoelectrically induced voltage of IPMC. However, the overall effect of the electrode surface structure is relatively low compared to the electromechanical transduction, which is in good agreement with theoretical prediction.

Discriminative clustering on manifold for adaptive transductive classification.

PubMed

Zhang, Zhao; Jia, Lei; Zhang, Min; Li, Bing; Zhang, Li; Li, Fanzhang

2017-10-01

In this paper, we mainly propose a novel adaptive transductive label propagation approach by joint discriminative clustering on manifolds for representing and classifying high-dimensional data. Our framework seamlessly combines the unsupervised manifold learning, discriminative clustering and adaptive classification into a unified model. Also, our method incorporates the adaptive graph weight construction with label propagation. Specifically, our method is capable of propagating label information using adaptive weights over low-dimensional manifold features, which is different from most existing studies that usually predict the labels and construct the weights in the original Euclidean space. For transductive classification by our formulation, we first perform the joint discriminative K-means clustering and manifold learning to capture the low-dimensional nonlinear manifolds. Then, we construct the adaptive weights over the learnt manifold features, where the adaptive weights are calculated through performing the joint minimization of the reconstruction errors over features and soft labels so that the graph weights can be joint-optimal for data representation and classification. Using the adaptive weights, we can easily estimate the unknown labels of samples. After that, our method returns the updated weights for further updating the manifold features. Extensive simulations on image classification and segmentation show that our proposed algorithm can deliver the state-of-the-art performance on several public datasets. Copyright © 2017 Elsevier Ltd. All rights reserved.

Signal transduction in T lymphocytes in microgravity

NASA Technical Reports Server (NTRS)

Cogoli, A.

1997-01-01

More than 120 experiments conducted in space in the last 15 years have shown that dramatic changes are occurring in several types of single cells during their exposure to microgravity. One focus of today's research on cells in space is on signal transduction, especially those steps involving the cytoskeleton and cell-cell interactions. Signal transduction is often altered in microgravity as well as in hypergravity. This leads to changes in cell proliferation, genetic expression and differentiation. Interesting examples are leukocytes, HeLa cells, epidermoid cells and osteoblastic cells. Signalling pathways were studied in T lymphocytes in microgravity by several investigators after the discovery that mitogenic activation in vitro is virtually nil at 0g. T cells are a good model to study signal transduction because three extracellular signals (mitogen, IL-1 and IL-2) are required for full activation, and two classical pathways (via proteins G and PKC) are activated within the cell. In addition, low molecular weight GTP-binding proteins (Ras and Rap) are interacting with the cytoskeleton. The data at 0g support the notion that the expression of IL-2 receptor is inhibited at 0g, while mitogen binding and the transmission of IL-1 by accessory cells occur normally. In addition, alterations of the cytoskeleton suggest that the interaction with Rap proteins is disturbed. Data obtained with phorbol esters indicate that the function of PKC is changed in microgravity. Similar conclusions are drawn from the results with epidermoid cells A431.

Falsification of the ionic channel theory of hair cell transduction

PubMed Central

Rossetto, Michelangelo

2013-01-01

The hair cell provides the transduction of mechanical vibrations in the balance and acoustic sense of all vertebrates that swim, walk, or fly. The current theory places hair cell transduction in a mechanically controlled ion channel. Although the theory of a mechanical input modulating the flow of ions through an ion pore has been a useful tool, it is falsified by experimental data in the literature and can be definitively falsified by a proposed experiment. PMID:24563711

Signal Transduction Pathways of TNAP: Molecular Network Analyses.

PubMed

Négyessy, László; Györffy, Balázs; Hanics, János; Bányai, Mihály; Fonta, Caroline; Bazsó, Fülöp

2015-01-01

Despite the growing body of evidence pointing on the involvement of tissue non-specific alkaline phosphatase (TNAP) in brain function and diseases like epilepsy and Alzheimer's disease, our understanding about the role of TNAP in the regulation of neurotransmission is severely limited. The aim of our study was to integrate the fragmented knowledge into a comprehensive view regarding neuronal functions of TNAP using objective tools. As a model we used the signal transduction molecular network of a pyramidal neuron after complementing with TNAP related data and performed the analysis using graph theoretic tools. The analyses show that TNAP is in the crossroad of numerous pathways and therefore is one of the key players of the neuronal signal transduction network. Through many of its connections, most notably with molecules of the purinergic system, TNAP serves as a controller by funnelling signal flow towards a subset of molecules. TNAP also appears as the source of signal to be spread via interactions with molecules involved among others in neurodegeneration. Cluster analyses identified TNAP as part of the second messenger signalling cascade. However, TNAP also forms connections with other functional groups involved in neuronal signal transduction. The results indicate the distinct ways of involvement of TNAP in multiple neuronal functions and diseases.

High-performance graphdiyne-based electrochemical actuators.

PubMed

Lu, Chao; Yang, Ying; Wang, Jian; Fu, Ruoping; Zhao, Xinxin; Zhao, Lei; Ming, Yue; Hu, Ying; Lin, Hongzhen; Tao, Xiaoming; Li, Yuliang; Chen, Wei

2018-02-21

Electrochemical actuators directly converting electrical energy to mechanical energy are critically important for artificial intelligence. However, their energy transduction efficiency is always lower than 1.0% because electrode materials lack active units in microstructure, and their assembly systems can hardly express the intrinsic properties. Here, we report a molecular-scale active graphdiyne-based electrochemical actuator with a high electro-mechanical transduction efficiency of up to 6.03%, exceeding that of the best-known piezoelectric ceramic, shape memory alloy and electroactive polymer reported before, and its energy density (11.5 kJ m -3 ) is comparable to that of mammalian skeletal muscle (~8 kJ m -3 ). Meanwhile, the actuator remains responsive at frequencies from 0.1 to 30 Hz with excellent cycling stability over 100,000 cycles. Furthermore, we verify the alkene-alkyne complex transition effect responsible for the high performance through in situ sum frequency generation spectroscopy. This discovery sheds light on our understanding of actuation mechanisms and will accelerate development of smart actuators.

Notch2 transduction by feline leukemia virus in a naturally infected cat.

PubMed

Watanabe, Shinya; Ito, Jumpei; Baba, Takuya; Hiratsuka, Takahiro; Kuse, Kyohei; Ochi, Haruyo; Anai, Yukari; Hisasue, Masaharu; Tsujimoto, Hajime; Nishigaki, Kazuo

2014-04-01

Feline leukemia virus (FeLV) induces neoplastic and nonneoplastic diseases in cats. The transduction of cellular genes by FeLV is sometimes observed and associated with neoplastic diseases including lymphoma and sarcoma. Here, we report the first natural case of feline Notch2 transduction by FeLV in an infected cat with multicentric lymphoma and hypercalcemia. We cloned recombinant FeLVs harboring Notch2 in the env gene. Notch2 was able to activate expression of a reporter gene, similar to what was previously reported in cats with experimental FeLV-induced thymic lymphoma. Our findings suggest that the transduction of Notch2 strongly correlates with FeLV-induced lymphoma.

Modelling protein functional domains in signal transduction using Maude

NASA Technical Reports Server (NTRS)

Sriram, M. G.

2003-01-01

Modelling of protein-protein interactions in signal transduction is receiving increased attention in computational biology. This paper describes recent research in the application of Maude, a symbolic language founded on rewriting logic, to the modelling of functional domains within signalling proteins. Protein functional domains (PFDs) are a critical focus of modern signal transduction research. In general, Maude models can simulate biological signalling networks and produce specific testable hypotheses at various levels of abstraction. Developing symbolic models of signalling proteins containing functional domains is important because of the potential to generate analyses of complex signalling networks based on structure-function relationships.

Studying Cellular Signal Transduction with OMIC Technologies.

PubMed

Landry, Benjamin D; Clarke, David C; Lee, Michael J

2015-10-23

In the gulf between genotype and phenotype exists proteins and, in particular, protein signal transduction systems. These systems use a relatively limited parts list to respond to a much longer list of extracellular, environmental, and/or mechanical cues with rapidity and specificity. Most signaling networks function in a highly non-linear and often contextual manner. Furthermore, these processes occur dynamically across space and time. Because of these complexities, systems and "OMIC" approaches are essential for the study of signal transduction. One challenge in using OMIC-scale approaches to study signaling is that the "signal" can take different forms in different situations. Signals are encoded in diverse ways such as protein-protein interactions, enzyme activities, localizations, or post-translational modifications to proteins. Furthermore, in some cases, signals may be encoded only in the dynamics, duration, or rates of change of these features. Accordingly, systems-level analyses of signaling may need to integrate multiple experimental and/or computational approaches. As the field has progressed, the non-triviality of integrating experimental and computational analyses has become apparent. Successful use of OMIC methods to study signaling will require the "right" experiments and the "right" modeling approaches, and it is critical to consider both in the design phase of the project. In this review, we discuss common OMIC and modeling approaches for studying signaling, emphasizing the philosophical and practical considerations for effectively merging these two types of approaches to maximize the probability of obtaining reliable and novel insights into signaling biology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Information content and cross-talk in biological signal transduction: An information theory study

NASA Astrophysics Data System (ADS)

Prasad, Ashok; Lyons, Samanthe

2014-03-01

Biological cells respond to chemical cues provided by extra-cellular chemical signals, but many of these chemical signals and the pathways they activate interfere and overlap with one another. How well cells can distinguish between interfering extra-cellular signals is thus an important question in cellular signal transduction. Here we use information theory with stochastic simulations of networks to address the question of what happens to total information content when signals interfere. We find that both total information transmitted by the biological pathway, as well as its theoretical capacity to discriminate between overlapping signals, are relatively insensitive to cross-talk between the extracellular signals, until significantly high levels of cross-talk have been reached. This robustness of information content against cross-talk requires that the average amplitude of the signals are large. We predict that smaller systems, as exemplified by simple phosphorylation relays (two-component systems) in bacteria, should be significantly much less robust against cross-talk. Our results suggest that mammalian signal transduction can tolerate a high amount of cross-talk without degrading information content, while smaller bacterial systems cannot.

Nonparametric Simulation of Signal Transduction Networks with Semi-Synchronized Update

PubMed Central

Nassiri, Isar; Masoudi-Nejad, Ali; Jalili, Mahdi; Moeini, Ali

2012-01-01

Simulating signal transduction in cellular signaling networks provides predictions of network dynamics by quantifying the changes in concentration and activity-level of the individual proteins. Since numerical values of kinetic parameters might be difficult to obtain, it is imperative to develop non-parametric approaches that combine the connectivity of a network with the response of individual proteins to signals which travel through the network. The activity levels of signaling proteins computed through existing non-parametric modeling tools do not show significant correlations with the observed values in experimental results. In this work we developed a non-parametric computational framework to describe the profile of the evolving process and the time course of the proportion of active form of molecules in the signal transduction networks. The model is also capable of incorporating perturbations. The model was validated on four signaling networks showing that it can effectively uncover the activity levels and trends of response during signal transduction process. PMID:22737250

E-cadherin-mediated force transduction signals regulate global cell mechanics

PubMed Central

Muhamed, Ismaeel; Wu, Jun; Sehgal, Poonam; Kong, Xinyu; Tajik, Arash; Wang, Ning

2016-01-01

ABSTRACT This report elucidates an E-cadherin-based force-transduction pathway that triggers changes in cell mechanics through a mechanism requiring epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase (PI3K), and the downstream formation of new integrin adhesions. This mechanism operates in addition to local cytoskeletal remodeling triggered by conformational changes in the E-cadherin-associated protein α-catenin, at sites of mechanical perturbation. Studies using magnetic twisting cytometry (MTC), together with traction force microscopy (TFM) and confocal imaging identified force-activated E-cadherin-specific signals that integrate cadherin force transduction, integrin activation and cell contractility. EGFR is required for the downstream activation of PI3K and myosin-II-dependent cell stiffening. Our findings also demonstrated that α-catenin-dependent cytoskeletal remodeling at perturbed E-cadherin adhesions does not require cell stiffening. These results broaden the repertoire of E-cadherin-based force transduction mechanisms, and define the force-sensitive signaling network underlying the mechano-chemical integration of spatially segregated adhesion receptors. PMID:26966187

A CRISPR-Based Toolbox for Studying T Cell Signal Transduction

PubMed Central

Chi, Shen; Weiss, Arthur; Wang, Haopeng

2016-01-01

CRISPR/Cas9 system is a powerful technology to perform genome editing in a variety of cell types. To facilitate the application of Cas9 in mapping T cell signaling pathways, we generated a toolbox for large-scale genetic screens in human Jurkat T cells. The toolbox has three different Jurkat cell lines expressing distinct Cas9 variants, including wild-type Cas9, dCas9-KRAB, and sunCas9. We demonstrated that the toolbox allows us to rapidly disrupt endogenous gene expression at the DNA level and to efficiently repress or activate gene expression at the transcriptional level. The toolbox, in combination with multiple currently existing genome-wide sgRNA libraries, will be useful to systematically investigate T cell signal transduction using both loss-of-function and gain-of-function genetic screens. PMID:27057542

Transduction of cultured fish cells with recombinant baculoviruses.

PubMed

Leisy, Douglas J; Lewis, Teresa D; Leong, Jo-Ann C; Rohrmann, George F

2003-05-01

Five fish cell lines were tested for their ability to be transduced by Ac-CAlacZ, a recombinant baculovirus that is capable of expressing a beta-galactosidase reporter gene from the CAG promoter (consisting of a cytomegalovirus enhancer element, a chicken actin promoter and rabbit beta-globin termination sequences). TO (Tilapia ovary), EPC (carp), CHH-1 (Chum salmon heart fibroblast) and CHSE-214 (chinook salmon embryo) cells were transducible, as demonstrated by an in situ beta-galactosidase assay, whereas RTG-2 (rainbow trout gonad) cells were not. The EPC cell line was used for more detailed studies on baculovirus transduction. The transduction frequency was found to be higher at 28 degrees C than at 21 degrees C. Addition of the histone deacetylase inhibitor sodium butyrate increased the number of blue cells detected 5- to 7-fold. The m.o.i. was positively correlated with transduction frequency, although the relationship did not appear to be strictly linear, as has been observed with mammalian cells. The temperature at which baculoviruses were adsorbed to EPC cells did not affect levels of beta-galactosidase expression. We also examined expression levels of beta-galactosidase in EPC cells after infection with a baculovirus construct that overexpresses the vesicular stomatitis virus G protein and displays it on the virion surface. Expression levels with this virus were approximately 15-fold higher than were observed with Ac-CAlacZ.

Revisiting Theories of Humidity Transduction: A Focus on Electrophysiological Data

PubMed Central

Tichy, Harald; Hellwig, Maria; Kallina, Wolfgang

2017-01-01

Understanding the mechanism of humidity transduction calls for experimental data and a theory to interpret the data and design new experiments. A comprehensive theory of humidity transduction must start with agreement on what humidity parameters are measured by hygroreceptors and processed by the brain. Hygroreceptors have been found in cuticular sensilla of a broad range of insect species. Their structural features are far from uniform. Nevertheless, these sensilla always contain an antagonistic pair of a moist cell and a dry cell combined with a thermoreceptive cold cell. The strategy behind this arrangement remains unclear. Three main models of humidity transduction have been proposed. Hygroreceptors could operate as mechanical hygrometers, psychrometers or evaporation detectors. Each mode of action measures a different humidity parameter. Mechanical hygrometers measure the relative humidity, psychrometers indicate the wet-bulb temperature, and evaporimeters refer to the saturation deficit of the air. Here we assess the validity of the different functions by testing specific predictions drawn from each of the models. The effect of air temperature on the responses to humidity stimulation rules out the mechanical hygrometer function, but it supports the psychrometer function and highlights the action as evaporation rate detector. We suggest testing the effect of the flow rate of the air stream used for humidity stimulation. As the wind speed strongly affects the power of evaporation, experiments with changing saturation deficit at different flow rates would improve our knowledge on humidity transduction. PMID:28928673

Revisiting Theories of Humidity Transduction: A Focus on Electrophysiological Data.

PubMed

Tichy, Harald; Hellwig, Maria; Kallina, Wolfgang

2017-01-01

Understanding the mechanism of humidity transduction calls for experimental data and a theory to interpret the data and design new experiments. A comprehensive theory of humidity transduction must start with agreement on what humidity parameters are measured by hygroreceptors and processed by the brain. Hygroreceptors have been found in cuticular sensilla of a broad range of insect species. Their structural features are far from uniform. Nevertheless, these sensilla always contain an antagonistic pair of a moist cell and a dry cell combined with a thermoreceptive cold cell. The strategy behind this arrangement remains unclear. Three main models of humidity transduction have been proposed. Hygroreceptors could operate as mechanical hygrometers, psychrometers or evaporation detectors. Each mode of action measures a different humidity parameter. Mechanical hygrometers measure the relative humidity, psychrometers indicate the wet-bulb temperature, and evaporimeters refer to the saturation deficit of the air. Here we assess the validity of the different functions by testing specific predictions drawn from each of the models. The effect of air temperature on the responses to humidity stimulation rules out the mechanical hygrometer function, but it supports the psychrometer function and highlights the action as evaporation rate detector. We suggest testing the effect of the flow rate of the air stream used for humidity stimulation. As the wind speed strongly affects the power of evaporation, experiments with changing saturation deficit at different flow rates would improve our knowledge on humidity transduction.

High Efficiency CRISPR/Cas9-mediated Gene Editing in Primary Human T-cells Using Mutant Adenoviral E4orf6/E1b55k "Helper" Proteins.

PubMed

Gwiazda, Kamila S; Grier, Alexandra E; Sahni, Jaya; Burleigh, Stephen M; Martin, Unja; Yang, Julia G; Popp, Nicholas A; Krutein, Michelle C; Khan, Iram F; Jacoby, Kyle; Jensen, Michael C; Rawlings, David J; Scharenberg, Andrew M

2016-09-29

Many future therapeutic applications of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 and related RNA-guided nucleases are likely to require their use to promote gene targeting, thus necessitating development of methods that provide for delivery of three components-Cas9, guide RNAs and recombination templates-to primary cells rendered proficient for homology-directed repair. Here, we demonstrate an electroporation/transduction codelivery method that utilizes mRNA to express both Cas9 and mutant adenoviral E4orf6 and E1b55k helper proteins in association with adeno-associated virus (AAV) vectors expressing guide RNAs and recombination templates. By transiently enhancing target cell permissiveness to AAV transduction and gene editing efficiency, this novel approach promotes efficient gene disruption and/or gene targeting at multiple loci in primary human T-cells, illustrating its broad potential for application in translational gene editing.

Bacteriophage Transduction in Staphylococcus aureus.

PubMed

Olson, Michael E

2016-01-01

The genetic manipulation of Staphylococcus aureus for molecular experimentation is a valuable tool for assessing gene function and virulence. Genetic variability between strains coupled with difficult laboratory techniques for strain construction is a frequent roadblock in S. aureus research. Bacteriophage transduction greatly increases the speed and ease of S. aureus studies by allowing movement of chromosomal markers and plasmids between strains. This technique enables the S. aureus research community to focus investigations on clinically relevant isolates.

Specific Retrograde Transduction of Spinal Motor Neurons Using Lentiviral Vectors Targeted to Presynaptic NMJ Receptors

PubMed Central

Eleftheriadou, I; Trabalza, A; Ellison, SM; Gharun, K; Mazarakis, ND

2014-01-01

To understand how receptors are involved in neuronal trafficking and to be able to utilize them for specific targeting via the peripheral route would be of great benefit. Here, we describe the generation of novel lentiviral vectors with tropism to motor neurons that were made by coexpressing onto the lentiviral surface a fusogenic glycoprotein (mutated sindbis G) and an antibody against a cell-surface receptor (Thy1.1, p75NTR, or coxsackievirus and adenovirus receptor) on the presynaptic terminal of the neuromuscular junction. These vectors exhibit binding specificity and efficient transduction of receptor positive cell lines and primary motor neurons in vitro. Targeting of each of these receptors conferred to these vectors the capability of being transported retrogradely from the axonal tip, leading to transduction of motor neurons in vitro in compartmented microfluidic cultures. In vivo delivery of coxsackievirus and adenovirus receptor-targeted vectors in leg muscles of mice resulted in predicted patterns of motor neuron labeling in lumbar spinal cord. This opens up the clinical potential of these vectors for minimally invasive administration of central nervous system-targeted therapeutics in motor neuron diseases. PMID:24670531

Vitamin E: A Role in Signal Transduction.

PubMed

Zingg, Jean-Marc

2015-01-01

Vitamin E modulates the activity of several signal transduction enzymes with consequent alterations of gene expression. At the molecular level, vitamin E may directly bind to these enzymes and compete with their substrates, or it may change their activity by redox regulation. The translocation of several of these enzymes to the plasma membrane is regulated by vitamin E, suggesting the modulation of protein-membrane interactions as a common mechanism for vitamin E action. Enzyme-membrane interactions can be affected by vitamin E by interference with binding to specific membrane lipids or by altering cellular structures such as membrane microdomains (lipid rafts). Moreover, competition by vitamin E for common binding sites within lipid transport proteins may alter the traffic of lipid mediators and thus affect their signaling and enzymatic conversion. In this review, the main effects of vitamin E on enzymes involved in signal transduction are summarized and possible molecular mechanisms leading to enzyme modulation are evaluated.

Transduction of NeuroD2 protein induced neural cell differentiation.

PubMed

Noda, Tomohide; Kawamura, Ryuzo; Funabashi, Hisakage; Mie, Masayasu; Kobatake, Eiry

2006-11-01

NeuroD2, one of the neurospecific basic helix-loop-helix transcription factors, has the ability to induce neural differentiation in undifferentiated cells. In this paper, we show that transduction of NeuroD2 protein induced mouse neuroblastoma cell line N1E-115 into neural differentiation. NeuroD2 has two basic-rich domains, one is nuclear localization signal (NLS) and the other is basic region of basic helix-loop-helix (basic). We constructed some mutants of NeuroD2, ND2(Delta100-115) (lack of NLS), ND2(Delta123-134) (lack of basic) and ND2(Delta100-134) (lack of both NLS and basic) for transduction experiments. Using these proteins, we have shown that NLS region of NeuroD2 plays a role of protein transduction. Continuous addition of NeuroD2 protein resulted in N1E-115 cells adopting neural morphology after 4 days and Tau mRNA expression was increased. These results suggest that neural differentiation can be induced by direct addition of NeuroD2 protein.

Insulin Therapy Improves Adeno-Associated Virus Transduction of Liver and Skeletal Muscle in Mice and Cultured Cells.

PubMed

Carrig, Sean; Bijjiga, Enoch; Wopat, Mitchell J; Martino, Ashley T

2016-11-01

Adeno-associated virus (AAV) gene transfer is a promising treatment for genetic abnormalities. Optimal AAV vectors are showing success in clinical trials. Gene transfer to skeletal muscle and liver is being explored as a potential therapy for some conditions, that is, α 1 -antitrypsin (AAT) disorder and hemophilia B. Exploring approaches that enhance transduction of liver and skeletal muscle, using these vectors, is beneficial for gene therapy. Regulating hormones as an approach to improve AAV transduction is largely unexplored. In this study we tested whether insulin therapy improves liver and skeletal muscle gene transfer. In vitro studies demonstrated that the temporary coadministration (2, 8, and 24 hr) of insulin significantly improves AAV2-CMV-LacZ transduction of cultured liver cells and differentiated myofibers, but not of lung cells. In addition, there was a dose response related to this improved transduction. Interestingly, when insulin was not coadministered with the virus but given 24 hr afterward, there was no increase in the transgene product. Insulin receptor gene (INSR) expression levels were increased 5- to 13-fold in cultured liver cells and differentiated myofibers when compared with lung cells. Similar INSR gene expression profiles occurred in mouse tissues. Insulin therapy was performed in mice, using a subcutaneously implanted insulin pellet or a high-carbohydrate diet. Insulin treatment began just before intramuscular delivery of AAV1-CMV-schFIX or liver-directed delivery of AAV8-CMV-schFIX and continued for 28 days. Both insulin augmentation therapies improved skeletal muscle- and liver-directed gene transduction in mice as seen by a 3.0- to 4.5-fold increase in human factor IX (hFIX) levels. The improvement was observed even after the insulin therapy ended. Monitoring insulin showed that insulin levels increased during the brief period of rAAV delivery and during the entire insulin augmentation period (28 days). This study demonstrates

Comparative biology of rAAV transduction in ferret, pig and human airway epithelia.

PubMed

Liu, X; Luo, M; Guo, C; Yan, Z; Wang, Y; Engelhardt, J F

2007-11-01

Differences between rodent and human airway cell biology have made it difficult to translate recombinant adeno-associated virus (rAAV)-mediated gene therapies to the lung for cystic fibrosis (CF). As new ferret and pig models for CF become available, knowledge about host cell/vector interactions in these species will become increasingly important for testing potential gene therapies. To this end, we have compared the transduction biology of three rAAV serotypes (AAV1, 2 and 5) in human, ferret, pig and mouse-polarized airway epithelia. Our results indicate that apical transduction of ferret and pig airway epithelia with these rAAV serotypes closely mirrors that observed in human epithelia (rAAV1>rAAV2 congruent withrAAV5), while transduction of mouse epithelia was significantly different (rAAV1>rAAV5>rAAV2). Similarly, ferret, pig and human epithelia also shared serotype-specific differences in the polarity (apical vs basolateral) and proteasome dependence of rAAV transduction. Despite these parallels, N-linked sialic acid receptors were required for rAAV1 and rAAV5 transduction of human and mouse airway epithelia, but not ferret or pig airway epithelia. Hence, although the airway tropisms of rAAV serotypes 1, 2 and 5 are conserved better among ferret, pig and human as compared to mouse, viral receptors/co-receptors appear to maintain considerable species diversity.

Ca2+-sensors and ROS-GC: interlocked sensory transduction elements: a review

PubMed Central

Sharma, Rameshwar K.; Duda, Teresa

2012-01-01

From its initial discovery that ROS-GC membrane guanylate cyclase is a mono-modal Ca2+-transduction system linked exclusively with the photo-transduction machinery to the successive finding that it embodies a remarkable bimodal Ca2+ signaling device, its widened transduction role in the general signaling mechanisms of the sensory neuron cells was envisioned. A theoretical concept was proposed where Ca2+-modulates ROS-GC through its generated cyclic GMP via a nearby cyclic nucleotide gated channel and creates a hyper- or depolarized sate in the neuron membrane (Ca2+ Binding Proteins 1:1, 7–11, 2006). The generated electric potential then becomes a mode of transmission of the parent [Ca2+]i signal. Ca2+ and ROS-GC are interlocked messengers in multiple sensory transduction mechanisms. This comprehensive review discusses the developmental stages to the present status of this concept and demonstrates how neuronal Ca2+-sensor (NCS) proteins are the interconnected elements of this elegant ROS-GC transduction system. The focus is on the dynamism of the structural composition of this system, and how it accommodates selectivity and elasticity for the Ca2+ signals to perform multiple tasks linked with the SENSES of vision, smell, and possibly of taste and the pineal gland. An intriguing illustration is provided for the Ca2+ sensor GCAP1 which displays its remarkable ability for its flexibility in function from being a photoreceptor sensor to an odorant receptor sensor. In doing so it reverses its function from an inhibitor of ROS-GC to the stimulator of ONE-GC membrane guanylate cyclase. PMID:22509149

Lipid and cationic polymer based transduction of botulinum holotoxin, or toxin protease alone, extends the target cell range and improves the efficiency of intoxication

PubMed Central

Kuo, Chueh-Ling; Oyler, George; Shoemaker, Charles B.

2009-01-01

Botulinum neurotoxin (BoNT) heavy chain (Hc) facilitates receptor-mediated endocytosis into neuronal cells and transport of the light chain (Lc) protease to the cytosol where neurotransmission is inhibited as a result of SNARE protein cleavage. Here we show that the role of BoNT Hc in cell intoxication can be replaced by commercial lipid-based and polycationic polymer DNA transfection reagents. BoNT “transduction” by these reagents permits efficient intoxication of neuronal cells as well as some non-neuronal cell lines normally refractory to BoNT. Surprisingly, the reagents facilitate delivery of recombinant BoNT Lc protease to the cytosol of both neuronal and non-neuronal cells in the absence of BoNT Hc, and with sensitivities approaching that of BoNT holotoxin. Transduction of BoNT, as with natural intoxication, is inhibited by bafilomycin A1, methylamine and ammonium chloride indicating that both pathways require endosome acidification. DNA transfection reagents facilitate intoxication by holotoxins, or isolated Lc proteases, of all three BoNT serotypes tested (A, B, E). These results suggest that lipid and cationic polymer transfection reagents facilitate cytosolic delivery of BoNT holotoxins and isolated Lc proteases by an endosomal uptake pathway. PMID:19852976

Novel Insights on Thyroid-Stimulating Hormone Receptor Signal Transduction

PubMed Central

Neumann, Susanne; Grüters, Annette; Krude, Heiko

2013-01-01

The TSH receptor (TSHR) is a member of the glycoprotein hormone receptors, a subfamily of family A G protein-coupled receptors. The TSHR is of great importance for the growth and function of the thyroid gland. The TSHR and its endogenous ligand TSH are pivotal proteins with respect to a variety of physiological functions and malfunctions. The molecular events of TSHR regulation can be summarized as a process of signal transduction, including signal reception, conversion, and amplification. The steps during signal transduction from the extra- to the intracellular sites of the cell are not yet comprehensively understood. However, essential new insights have been achieved in recent years on the interrelated mechanisms at the extracellular region, the transmembrane domain, and intracellular components. This review contains a critical summary of available knowledge of the molecular mechanisms of signal transduction at the TSHR, for example, the key amino acids involved in hormone binding or in the structural conformational changes that lead to G protein activation or signaling regulation. Aspects of TSHR oligomerization, signaling promiscuity, signaling selectivity, phenotypes of genetic variations, and potential extrathyroidal receptor activity are also considered, because these are relevant to an understanding of the overall function of the TSHR, including physiological, pathophysiological, and pharmacological perspectives. Directions for future research are discussed. PMID:23645907

Nucleotide Signaling and Cutaneous Mechanisms of Pain Transduction

PubMed Central

Dussor, G.; Koerber, H.R.; Oaklander, AL; Rice, F.L.; Molliver, D.C.

2009-01-01

Sensory neurons that innervate the skin provide critical information about physical contact between the organism and the environment, including information about potentially-damaging stimuli that give rise to the sensation of pain. These afferents also contribute to the maintenance of tissue homeostasis, inflammation and wound healing, while sensitization of sensory afferents after injury results in painful hypersensitivity and protective behavior. In contrast to the traditional view of primary afferent terminals as the sole site of sensory transduction, recent reports have lead to the intriguing idea that cells of the skin play an active role in the transduction of sensory stimuli. The search for molecules that transduce different types of sensory stimuli (mechanical, heat, chemical) at the axon terminal has yielded a wide range of potential effectors, many of which are expressed by keratinocytes as well as neurons. Emerging evidence underscores the importance of nucleotide signaling through P2X ionotropic and P2Y metabotropic receptors in pain processing, and implicates nucleotide signaling as a critical form of communication between cells of the skin, immune cells and sensory neurons. It is of great interest to determine whether pathological changes in these mechanisms contribute to chronic pain in human disease states such as complex regional pain syndrome (CRPS). This review discusses recent advances in our understanding of communication mechanisms between cells of the skin and sensory axons in the transduction of sensory input leading to pain. PMID:19171165

[Signal transduction mechanisms of hormones through membrane receptors].

PubMed

Yasufuku-Takano, Junko; Takano, Koji

2002-02-01

Hormones exert their effect on cells either via membrane receptors or intracellular receptors. This paper aims to review membrane receptors and the intracellular signal transduction mechanisms. Membrane receptors could be classified according to their structural characteristics and the way they initiate the intracellular signal transduction. These include 1) Seven transmembrane(or G-protein coupled) receptors--heterotrimeric G-proteins--effector, system, 2) Receptor tyrosine kinases--protein-protein interaction through SH2, SH3, and PTB domain--MAP kinase cascades and PI3-kinase pathways, 3) Cytokine receptors--JAK--STAT pathways, 4) Receptors of the TGF- beta superfamily--SMAD pathways, 5) Apoptosis-related receptors--caspase pathways, and 6) ligand-gated ion channels. There are growing knowledge of cross-talks between these pathways. It is being recognized that steroid hormones have distinct membrane receptors, which mediate rapid, nongenomic effect.

Progress of OLED devices with high efficiency at high luminance

NASA Astrophysics Data System (ADS)

Nguyen, Carmen; Ingram, Grayson; Lu, Zhenghong

2014-03-01

Organic light emitting diodes (OLEDs) have progressed significantly over the last two decades. For years, OLEDs have been promoted as the next generation technology for flat panel displays and solid-state lighting due to their potential for high energy efficiency and dynamic range of colors. Although high efficiency can readily be obtained at low brightness levels, a significant decline at high brightness is commonly observed. In this report, we will review various strategies for achieving highly efficient phosphorescent OLED devices at high luminance. Specifically, we will provide details regarding the performance and general working principles behind each strategy. We will conclude by looking at how some of these strategies can be combined to produce high efficiency white OLEDs at high brightness.

Simulation of the real efficiencies of high-efficiency silicon solar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sachenko, A. V., E-mail: sach@isp.kiev.ua; Skrebtii, A. I.; Korkishko, R. M.

The temperature dependences of the efficiency η of high-efficiency solar cells based on silicon are calculated. It is shown that the temperature coefficient of decreasing η with increasing temperature decreases as the surface recombination rate decreases. The photoconversion efficiency of high-efficiency silicon-based solar cells operating under natural (field) conditions is simulated. Their operating temperature is determined self-consistently by simultaneously solving the photocurrent, photovoltage, and energy-balance equations. Radiative and convective cooling mechanisms are taken into account. It is shown that the operating temperature of solar cells is higher than the ambient temperature even at very high convection coefficients (~300 W/m{sup 2}more » K). Accordingly, the photoconversion efficiency in this case is lower than when the temperature of the solar cells is equal to the ambient temperature. The calculated dependences for the open-circuit voltage and the photoconversion efficiency of high-quality silicon solar cells under concentrated illumination are discussed taking into account the actual temperature of the solar cells.« less

Structural insight into partner specificity and phosphoryl transfer in two-component signal transduction.

PubMed

Casino, Patricia; Rubio, Vicente; Marina, Alberto

2009-10-16

The chief mechanism used by bacteria for sensing their environment is based on two conserved proteins: a sensor histidine kinase (HK) and an effector response regulator (RR). The signal transduction process involves highly conserved domains of both proteins that mediate autokinase, phosphotransfer, and phosphatase activities whose output is a finely tuned RR phosphorylation level. Here, we report the structure of the complex between the entire cytoplasmic portion of Thermotoga maritima class I HK853 and its cognate, RR468, as well as the structure of the isolated RR468, both free and BeF(3)(-) bound. Our results provide insight into partner specificity in two-component systems, recognition of the phosphorylation state of each partner, and the catalytic mechanism of the phosphatase reaction. Biochemical analysis shows that the HK853-catalyzed autokinase reaction proceeds by a cis autophosphorylation mechanism within the HK subunit. The results suggest a model for the signal transduction mechanism in two-component systems.

Dynamic pathway modeling of signal transduction networks: a domain-oriented approach.

PubMed

Conzelmann, Holger; Gilles, Ernst-Dieter

2008-01-01

Mathematical models of biological processes become more and more important in biology. The aim is a holistic understanding of how processes such as cellular communication, cell division, regulation, homeostasis, or adaptation work, how they are regulated, and how they react to perturbations. The great complexity of most of these processes necessitates the generation of mathematical models in order to address these questions. In this chapter we provide an introduction to basic principles of dynamic modeling and highlight both problems and chances of dynamic modeling in biology. The main focus will be on modeling of s transduction pathways, which requires the application of a special modeling approach. A common pattern, especially in eukaryotic signaling systems, is the formation of multi protein signaling complexes. Even for a small number of interacting proteins the number of distinguishable molecular species can be extremely high. This combinatorial complexity is due to the great number of distinct binding domains of many receptors and scaffold proteins involved in signal transduction. However, these problems can be overcome using a new domain-oriented modeling approach, which makes it possible to handle complex and branched signaling pathways.

Adeno-associated virus (AAV)-3-based vectors transduce haematopoietic cells not susceptible to transduction with AAV-2-based vectors.

PubMed

Handa, A; Muramatsu, S; Qiu, J; Mizukami, H; Brown, K E

2000-08-01

Although adeno-associated virus (AAV)-2 has a broad tissue-host range and can transduce a wide variety of tissue types, some cells, such as erythro-megakaryoblastoid cells, are non-permissive and appear to lack the AAV-2 receptor. However, limited studies have been reported with the related dependovirus AAV-3. We have previously cloned this virus, characterized its genome and produced an infectious clone. In this study, the gene for green fluorescent protein (GFP) was inserted into AAV-2- and AAV-3-based plasmids and recombinant viruses were produced. These viruses were then used to transduce haematopoietic cells and the transduction efficiencies were compared. In contrast to recombinant (r) AAV-2, rAAV-3 successfully transduced erythroid and megakaryoblastoid cells, although rAAV-2 was superior in transduction of lymphocyte-derived cell lines. Recently, it was reported that heparan sulphate can act as a receptor of AAV-2. The infectivity of rAAV-2 and rAAV-3 was tested with mutant cell lines of Chinese hamster ovary cells that were defective for heparin or heparan sulphate expression on the cell surface. There was no correlation between the ability of rAAV-2 or rAAV-3 to infect cells and the cell surface expression of heparan sulphate and, although heparin blocked both rAAV-2 and rAAV-3 transduction, the ID(50) of rAAV-3 was higher than that of rAAV-2. In addition, virus-binding overlay assays indicated that AAV-2 and AAV-3 bound different membrane proteins. These results suggest not only that there are different cellular receptors for AAV-2 and AAV-3, but that rAAV-3 vectors may be preferred for transduction of some haematopoietic cell types.

Adeno-associated virus vector-mediated transduction in the cat brain.

PubMed

Vite, Charles H; Passini, Marco A; Haskins, Mark E; Wolfe, John H

2003-10-01

Adeno-associated virus (AAV) vectors are capable of delivering a therapeutic gene to the mouse brain that can result in long-term and widespread protein production. However, the human infant brain is more than 1000 times larger than the mouse brain, which will make the treatment of global neurometabolic disorders in children more difficult. In this study, we evaluated the ability of three AAV serotypes (1,2, and 5) to transduce cells in the cat brain as a model of a large mammalian brain. The human lysosomal enzyme beta-glucuronidase (GUSB) was used as a reporter gene, because it can be distinguished from feline GUSB by heat stability. The vectors were injected into the cerebral cortex, caudate nucleus, thalamus, corona radiata, internal capsule, and centrum semiovale of 8-week-old cats. The brains were evaluated for gene expression using in situ hybridization and enzyme histochemistry 10 weeks after surgery. The AAV2 vector was capable of transducing cells in the gray matter, while the AAV1 vector resulted in greater transduction of the gray matter than AAV2 as well as transduction of the white matter. AAV5 did not result in detectable transduction in the cat brain.

Interplay between sugar and hormone signaling pathways modulate floral signal transduction

PubMed Central

Matsoukas, Ianis G.

2014-01-01

NOMENCLATURE The following nomenclature will be used in this article: Names of genes are written in italicized upper-case letters, e.g., ABI4.Names of proteins are written in non-italicized upper-case letters, e.g., ABI4.Names of mutants are written in italicized lower-case letters, e.g., abi4. The juvenile-to-adult and vegetative-to-reproductive phase transitions are major determinants of plant reproductive success and adaptation to the local environment. Understanding the intricate molecular genetic and physiological machinery by which environment regulates juvenility and floral signal transduction has significant scientific and economic implications. Sugars are recognized as important regulatory molecules that regulate cellular activity at multiple levels, from transcription and translation to protein stability and activity. Molecular genetic and physiological approaches have demonstrated different aspects of carbohydrate involvement and its interactions with other signal transduction pathways in regulation of the juvenile-to-adult and vegetative-to-reproductive phase transitions. Sugars regulate juvenility and floral signal transduction through their function as energy sources, osmotic regulators and signaling molecules. Interestingly, sugar signaling has been shown to involve extensive connections with phytohormone signaling. This includes interactions with phytohormones that are also important for the orchestration of developmental phase transitions, including gibberellins, abscisic acid, ethylene, and brassinosteroids. This article highlights the potential roles of sugar-hormone interactions in regulation of floral signal transduction, with particular emphasis on Arabidopsis thaliana mutant phenotypes, and suggests possible directions for future research. PMID:25165468

Interplay between sugar and hormone signaling pathways modulate floral signal transduction.

PubMed

Matsoukas, Ianis G

2014-01-01

NOMENCLATURE The following nomenclature will be used in this article: Names of genes are written in italicized upper-case letters, e.g., ABI4.Names of proteins are written in non-italicized upper-case letters, e.g., ABI4.Names of mutants are written in italicized lower-case letters, e.g., abi4. The juvenile-to-adult and vegetative-to-reproductive phase transitions are major determinants of plant reproductive success and adaptation to the local environment. Understanding the intricate molecular genetic and physiological machinery by which environment regulates juvenility and floral signal transduction has significant scientific and economic implications. Sugars are recognized as important regulatory molecules that regulate cellular activity at multiple levels, from transcription and translation to protein stability and activity. Molecular genetic and physiological approaches have demonstrated different aspects of carbohydrate involvement and its interactions with other signal transduction pathways in regulation of the juvenile-to-adult and vegetative-to-reproductive phase transitions. Sugars regulate juvenility and floral signal transduction through their function as energy sources, osmotic regulators and signaling molecules. Interestingly, sugar signaling has been shown to involve extensive connections with phytohormone signaling. This includes interactions with phytohormones that are also important for the orchestration of developmental phase transitions, including gibberellins, abscisic acid, ethylene, and brassinosteroids. This article highlights the potential roles of sugar-hormone interactions in regulation of floral signal transduction, with particular emphasis on Arabidopsis thaliana mutant phenotypes, and suggests possible directions for future research.

Sensory Transduction and Electrical Signaling in Guard Cells

PubMed Central

Serrano, Elba E.; Zeiger, Eduardo

1989-01-01

Guard cells are a valuable model system for the study of photoreception, ion transport, and osmoregulation in plant cells. Changes in stomatal apertures occur when sensing mechanisms within the guard cells transduce environmental stimull into the ion fluxes and biosynthesis of organic solutes that regulate turgor. The electrical events mediating sensory transduction in guard cells can be characterized with a variety of electrophysiological recording techniques. Recent experiments applying the patch clamp method to guard cell protoplasts have demonstrated activation of electrogenic pumps by blue and red light as well as the presence of potassium channels in guard cell plasmalemma. Light activation of electrogenic proton pumping and the ensuing gating of voltage-dependent ion channels appear to be components of sensory transduction of the stomatal response to light. Mechanisms underlying stomatal control by environmental signals can be understood by studying electrical events associated with ion transport. PMID:16667138

The role of viscous fluid flow in cochlear partition transduction

NASA Astrophysics Data System (ADS)

Svobodny, Thomas

2002-11-01

Sound transduction occurs via the forcing of the basilar membrane by a wave set up in the cochlear chamber. At the threshold of hearing the amplitude of the vibrations is on the nanometer scale. Fluid flow in this chamber is at very low Reynolds number. The actual transduction occurs through the mechanism of stereocilia of hair cells. We will describe the three-dimensional distribution of energy and how fluid flow affects stereociliar deflection due to the influence of the dynamics of the endothelial fluid. This talk will emphasis the results of two-dimensional and three-dimensional simulations and will relate these to the analytical solutions previously reported.

Genetic modification of adeno-associated viral vector type 2 capsid enhances gene transfer efficiency in polarized human airway epithelial cells.

PubMed

White, April F; Mazur, Marina; Sorscher, Eric J; Zinn, Kurt R; Ponnazhagan, Selvarangan

2008-12-01

Cystic fibrosis (CF) is a common genetic disease characterized by defects in the expression of the CF transmembrane conductance regulator (CFTR) gene. Gene therapy offers better hope for the treatment of CF. Adeno-associated viral (AAV) vectors are capable of stable expression with low immunogenicity. Despite their potential in CF gene therapy, gene transfer efficiency by AAV is limited because of pathophysiological barriers in these patients. Although a few AAV serotypes have shown better transduction compared with the AAV2-based vectors, gene transfer efficiency in human airway epithelium has still not reached therapeutic levels. To engineer better AAV vectors for enhanced gene delivery in human airway epithelium, we developed and characterized mutant AAV vectors by genetic capsid modification, modeling the well-characterized AAV2 serotype. We genetically incorporated putative high-affinity peptide ligands to human airway epithelium on the GH loop region of AAV2 capsid protein. Six independent mutant AAV were constructed, containing peptide ligands previously reported to bind with high affinity for known and unknown receptors on human airway epithelial cells. The vectors were tested on nonairway cells and nonpolarized and polarized human airway epithelial cells for enhanced infectivity. One of the mutant vectors, with the peptide sequence THALWHT, not only showed the highest transduction in undifferentiated human airway epithelial cells but also indicated significant transduction in polarized cells. Interestingly, this modified vector was also able to infect cells independently of the heparan sulfate proteoglycan receptor. Incorporation of this ligand on other AAV serotypes, which have shown improved gene transfer efficiency in the human airway epithelium, may enhance the application of AAV vectors in CF gene therapy.

Sympathetic vascular transduction is augmented in young normotensive blacks

NASA Technical Reports Server (NTRS)

Ray, Chester A.; Monahan, Kevin D.

2002-01-01

The purpose of the present study was to determine sympathetic vascular transduction in young normotensive black and white adults. We hypothesized that blacks would demonstrate augmented transduction of muscle sympathetic nerve activity (MSNA) into vascular resistance. To test this hypothesis, MSNA, forearm blood flow, heart rate, and arterial blood pressure were measured during lower body negative pressure (LBNP). At rest, no differences existed in arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance (FVR). Likewise, LBNP elicited comparable responses of these variables for blacks and whites. Baseline MSNA did not differ between blacks and whites, but whites demonstrated greater increases during LBNP (28 +/- 7 vs. 55 +/- 18%, 81 +/- 21 vs. 137 +/- 42%, 174 +/- 81 vs. 556 +/- 98% for -5, -15, and -40 mmHg LBNP, respectively; P < 0.001). Consistent with smaller increases in MSNA but similar FVR responses during LBNP, blacks demonstrated greater sympathetic vascular transduction (%FVR/%MSNA) than whites (0.95 +/- 0.07 vs. 0.82 +/- 0.07 U; 0.82 +/- 0.11 vs. 0.64 +/- 0.09 U; 0.95 +/- 0.37 vs. 0.35 +/- 0.09 U; P < 0.01). In summary, young whites demonstrate greater increases in MSNA during baroreceptor unloading than age-matched normotensive blacks. However, more importantly, for a given increase in MSNA, blacks demonstrate greater forearm vasoconstriction than whites. This finding may contribute to augmented blood pressure reactivity in blacks.

Proposed Role for KaiC-Like ATPases as Major Signal Transduction Hubs in Archaea

PubMed Central

2017-01-01

ABSTRACT All organisms must adapt to ever-changing environmental conditions and accordingly have evolved diverse signal transduction systems. In bacteria, the most abundant networks are built around the two-component signal transduction systems that include histidine kinases and receiver domains. In contrast, eukaryotic signal transduction is dominated by serine/threonine/tyrosine protein kinases. Both of these systems are also found in archaea, but they are not as common and diversified as their bacterial and eukaryotic counterparts, suggesting the possibility that archaea have evolved other, still uncharacterized signal transduction networks. Here we propose a role for KaiC family ATPases, known to be key components of the circadian clock in cyanobacteria, in archaeal signal transduction. The KaiC family is notably expanded in most archaeal genomes, and although most of these ATPases remain poorly characterized, members of the KaiC family have been shown to control archaellum assembly and have been found to be a stable component of the gas vesicle system in Halobacteria. Computational analyses described here suggest that KaiC-like ATPases and their homologues with inactivated ATPase domains are involved in many other archaeal signal transduction pathways and comprise major hubs of complex regulatory networks. We predict numerous input and output domains that are linked to KaiC-like proteins, including putative homologues of eukaryotic DEATH domains that could function as adapters in archaeal signaling networks. We further address the relationships of the archaeal family of KaiC homologues to the bona fide KaiC of cyanobacteria and implications for the existence of a KaiC-based circadian clock apparatus in archaea. PMID:29208747

High efficiency quantum cascade laser frequency comb.

PubMed

Lu, Quanyong; Wu, Donghai; Slivken, Steven; Razeghi, Manijeh

2017-03-06

An efficient mid-infrared frequency comb source is of great interest to high speed, high resolution spectroscopy and metrology. Here we demonstrate a mid-IR quantum cascade laser frequency comb with a high power output and narrow beatnote linewidth at room temperature. The active region was designed with a strong-coupling between the injector and the upper lasing level for high internal quantum efficiency and a broadband gain. The group velocity dispersion was engineered for efficient, broadband mode-locking via four wave mixing. The comb device exhibits a narrow intermode beatnote linewidth of 50.5 Hz and a maximum wall-plug efficiency of 6.5% covering a spectral coverage of 110 cm -1 at λ ~ 8 μm. The efficiency is improved by a factor of 6 compared with previous demonstrations. The high power efficiency and narrow beatnote linewidth will greatly expand the applications of quantum cascade laser frequency combs including high-precision remote sensing and spectroscopy.

High efficiency quantum cascade laser frequency comb

PubMed Central

Lu, Quanyong; Wu, Donghai; Slivken, Steven; Razeghi, Manijeh

2017-01-01

An efficient mid-infrared frequency comb source is of great interest to high speed, high resolution spectroscopy and metrology. Here we demonstrate a mid-IR quantum cascade laser frequency comb with a high power output and narrow beatnote linewidth at room temperature. The active region was designed with a strong-coupling between the injector and the upper lasing level for high internal quantum efficiency and a broadband gain. The group velocity dispersion was engineered for efficient, broadband mode-locking via four wave mixing. The comb device exhibits a narrow intermode beatnote linewidth of 50.5 Hz and a maximum wall-plug efficiency of 6.5% covering a spectral coverage of 110 cm−1 at λ ~ 8 μm. The efficiency is improved by a factor of 6 compared with previous demonstrations. The high power efficiency and narrow beatnote linewidth will greatly expand the applications of quantum cascade laser frequency combs including high-precision remote sensing and spectroscopy. PMID:28262834

Cell biology symposium: Membrane trafficking and signal transduction

USDA-ARS?s Scientific Manuscript database

In general, membrane trafficking is a broad group of processes where proteins and other large molecules are distributed throughout the cell as well as adjacent extracellular spaces. Whereas signal transduction is a process where signals are transmitted through a series of chemical or molecular event...

Enhanced radiosensitivity of malignant glioma cells after adenoviral p53 transduction.

PubMed

Broaddus, W C; Liu, Y; Steele, L L; Gillies, G T; Lin, P S; Loudon, W G; Valerie, K; Schmidt-Ullrich, R K; Fillmore, H L

1999-12-01

The goal of this study was to determine whether adenoviral vector-mediated expression of human wildtype p53 can enhance the radiosensitivity of malignant glioma cells that express native wild-type p53. The p53 gene is thought to function abnormally in the majority of malignant gliomas, although it has been demonstrated to be mutated in only approximately 30%. This has led to studies in which adenoviral transduction with wild-type human p53 has been investigated in an attempt to slow tumor cell growth. Recent studies suggest that reconstitution of wild-type p53 can render cells more susceptible to radiation-mediated death, primarily by p53-mediated apoptosis. Rat RT2 glioma cells were analyzed for native p53 status by reverse transcriptase-polymerase chain reaction and sequence analysis and for p53 expression by Western blot analysis. Clonogenic survival and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were used to characterize RT2 cell radiosensitivity and apoptosis, respectively, with and without prior transduction with p53-containing and control adenoviral vectors. Animal survival length was monitored after intracerebral implantation with transduced and nontransduced RT2 cells, with and without cranial radiation. The RT2 cells were demonstrated to express native rat wild-type p53 and to markedly overexpress human p53 following adenoviral p53 transduction. The combination of p53 transduction followed by radiation resulted in marked decreases in RT2 cell survival and increases in apoptosis at radiation doses from 2 to 6 Gy. Animals receiving cranial radiation after intracerebral implantation with RT2 cells previously transduced with p53 survived significantly longer than control animals (p<0.01). The ability to enhance the radiosensitivity of malignant glioma cells that express wild-type p53 by using adenoviral transduction to induce overexpression of p53 offers hope for this approach as a therapeutic strategy

High-Dimensional Mutant and Modular Thermodynamic Cycles, Molecular Switching, and Free Energy Transduction

PubMed Central

Carter, Charles W.

2017-01-01

Understanding how distinct parts of proteins produce coordinated behavior has driven and continues to drive advances in protein science and enzymology. However, despite consensus about the conceptual basis for allostery, the idiosyncratic nature of allosteric mechanisms resists general approaches. Computational methods can identify conformational transition states from structural changes, revealing common switching mechanisms that impose multistate behavior. Thermodynamic cycles use factorial perturbations to measure coupling energies between side chains in molecular switches that mediate shear during domain motion. Such cycles have now been complemented by modular cycles that measure energetic coupling between separable domains. For one model system, energetic coupling between domains has been shown to be quantitatively equivalent to that between dynamic side chains. Linkages between domain motion, switching residues, and catalysis make nucleoside triphosphate hydrolysis conditional on domain movement, confirming an essential yet neglected aspect of free energy transduction and suggesting the potential generality of these studies. PMID:28375734

Linear models of activation cascades: analytical solutions and coarse-graining of delayed signal transduction

PubMed Central

Desikan, Radhika

2016-01-01

Cellular signal transduction usually involves activation cascades, the sequential activation of a series of proteins following the reception of an input signal. Here, we study the classic model of weakly activated cascades and obtain analytical solutions for a variety of inputs. We show that in the special but important case of optimal gain cascades (i.e. when the deactivation rates are identical) the downstream output of the cascade can be represented exactly as a lumped nonlinear module containing an incomplete gamma function with real parameters that depend on the rates and length of the cascade, as well as parameters of the input signal. The expressions obtained can be applied to the non-identical case when the deactivation rates are random to capture the variability in the cascade outputs. We also show that cascades can be rearranged so that blocks with similar rates can be lumped and represented through our nonlinear modules. Our results can be used both to represent cascades in computational models of differential equations and to fit data efficiently, by reducing the number of equations and parameters involved. In particular, the length of the cascade appears as a real-valued parameter and can thus be fitted in the same manner as Hill coefficients. Finally, we show how the obtained nonlinear modules can be used instead of delay differential equations to model delays in signal transduction. PMID:27581482

High efficiency solar cell processing

NASA Technical Reports Server (NTRS)

Ho, F.; Iles, P. A.

1985-01-01

At the time of writing, cells made by several groups are approaching 19% efficiency. General aspects of the processing required for such cells are discussed. Most processing used for high efficiency cells is derived from space-cell or concentrator cell technology, and recent advances have been obtained from improved techniques rather than from better understanding of the limiting mechanisms. Theory and modeling are fairly well developed, and adequate to guide further asymptotic increases in performance of near conventional cells. There are several competitive cell designs with promise of higher performance ( 20%) but for these designs further improvements are required. The available cell processing technology to fabricate high efficiency cells is examined.

Syngeneic AAV pseudo-vectors potentiates full vector transduction

USDA-ARS?s Scientific Manuscript database

An excessive amount of empty capsids are generated during regular AAV vector production process. These pseudo-vectors often remain in final vectors used for animal studies or clinical trials. The potential effects of these pseudo-vectors on AAV transduction have been a major concern. In the current ...

[Characteristics of phosphorus uptake and use efficiency of rice with high yield and high phosphorus use efficiency].

PubMed

Li, Li; Zhang, Xi-Zhou; Li, Tinx-Xuan; Yu, Hai-Ying; Ji, Lin; Chen, Guang-Deng

2014-07-01

A total of twenty seven middle maturing rice varieties as parent materials were divided into four types based on P use efficiency for grain yield in 2011 by field experiment with normal phosphorus (P) application. The rice variety with high yield and high P efficiency was identified by pot experiment with normal and low P applications, and the contribution rates of various P efficiencies to yield were investigated in 2012. There were significant genotype differences in yield and P efficiency of the test materials. GRLu17/AiTTP//Lu17_2 (QR20) was identified as a variety with high yield and high P efficiency, and its yields at the low and normal rates of P application were 1.96 and 1.92 times of that of Yuxiang B, respectively. The contribution rate of P accumulation to yield was greater than that of P grain production efficiency and P harvest index across field and pot experiments. The contribution rates of P accumulation and P grain production efficiency to yield were not significantly different under the normal P condition, whereas obvious differences were observed under the low P condition (66.5% and 26.6%). The minimal contribution to yield was P harvest index (11.8%). Under the normal P condition, the contribution rates of P accumulation to yield and P harvest index were the highest at the jointing-heading stage, which were 93.4% and 85.7%, respectively. In addition, the contribution rate of P accumulation to grain production efficiency was 41.8%. Under the low P condition, the maximal contribution rates of P accumulation to yield and grain production efficiency were observed at the tillering-jointing stage, which were 56.9% and 20.1% respectively. Furthermore, the contribution rate of P accumulation to P harvest index was 16.0%. The yield, P accumulation, and P harvest index of QR20 significantly increased under the normal P condition by 20.6%, 18.1% and 18.2% respectively compared with that in the low P condition. The rank of the contribution rates of P

Genetic analysis of gravity signal transduction in roots

NASA Astrophysics Data System (ADS)

Masson, Patrick; Strohm, Allison; Baldwin, Katherine

To grow downward into the soil, roots use gravity as a guide. Specialized cells, named stato-cytes, enable this directional growth response by perceiving gravity. Located in the columella region of the cap, these cells sense a reorientation of the root within the gravity field through the sedimentation of, and/or tension/pressure exerted by, dense amyloplasts. This process trig-gers a gravity signal transduction pathway that leads to a fast alkalinization of the cytoplasm and a change in the distribution of the plasma membrane-associated auxin-efflux carrier PIN3. The latter protein is uniformly distributed within the plasma membrane on all sides of the cell in vertically oriented roots. However, it quickly accumulates at the bottom side upon gravis-timulation. This process correlates with a preferential transport of auxin to the bottom side of the root cap, resulting in a lateral gradient across the tip. This gradient is then transported to the elongation zone where it promotes differential cellular elongation, resulting in downward curvature. We isolated mutations that affect gravity signal transduction at a step that pre-cedes cytoplasmic alkalinization and/or PIN3 relocalization and lateral auxin transport across the cap. arg1 and arl2 mutations identify a common genetic pathway that is needed for all three gravity-induced processes in the cap statocytes, indicating these genes function early in the pathway. On the other hand, adk1 affects gravity-induced PIN3 relocalization and lateral auxin transport, but it does not interfere with cytoplasmic alkalinization. ARG1 and ARL2 encode J-domain proteins that are associated with membranes of the vesicular trafficking path-way whereas ADK1 encodes adenosine kinase, an enzyme that converts adenosine derived from nucleic acid metabolism and the AdoMet cycle into AMP, thereby alleviating feedback inhibi-tion of this important methyl-donor cycle. Because mutations in ARG1 (and ARL2) do not completely eliminate

High-efficiency, broad band, high-damage threshold high-index gratings for femtosecond pulse compression.

PubMed

Canova, Frederico; Clady, Raphael; Chambaret, Jean-Paul; Flury, Manuel; Tonchev, Svtelen; Fechner, Renate; Parriaux, Olivier

2007-11-12

High efficiency, broad-band TE-polarization diffraction over a wavelength range centered at 800 nm is obtained by high index gratings placed on a non-corrugated mirror. More than 96% efficiency wide band top-hat diffraction efficiency spectra, as well as more than 1 J/cm(2) damage threshold under 50 fs pulses are demonstrated experimentally. This opens the way to high-efficiency Chirped Pulse Amplification for high average power laser machining by means of all-dielectric structures as well as for ultra-short high energy pulses by means of metal-dielectric structures.

Expansion of signal transduction pathways in fungi by extensive genome duplication

PubMed Central

Corrochano, Luis M.; Kuo, Alan; Marcet-Houben, Marina; Polaino, Silvia; Salamov, Asaf; Villalobos-Escobedo, José M.; Grimwood, Jane; Álvarez, M. Isabel; Avalos, Javier; Bauer, Diane; Benito, Ernesto P.; Benoit, Isabelle; Burger, Gertraud; Camino, Lola P.; Cánovas, David; Cerdá-Olmedo, Enrique; Cheng, Jan-Fang; Domínguez, Angel; Eliáš, Marek; Eslava, Arturo P.; Glaser, Fabian; Gutiérrez, Gabriel; Heitman, Joseph; Henrissat, Bernard; Iturriaga, Enrique A.; Lang, B. Franz; Lavín, José L.; Lee, Soo Chan; Li, Wenjun; Lindquist, Erika; López-García, Sergio; Luque, Eva M.; Marcos, Ana T.; Martin, Joel; McCluskey, Kevin; Medina, Humberto R.; Miralles-Durán, Alejandro; Miyazaki, Atsushi; Muñoz-Torres, Elisa; Oguiza, José A.; Ohm, Robin A.; Orejas, Margarita; Ortiz-Castellanos, Lucila; Pisabarro, Antonio G.; Rodríguez-Romero, Julio; Ruiz-Herrera, José; Ruiz-Vázquez, Rosa; Sanz, Catalina; Schackwitz, Wendy; Shahriari, Mahdi; Shelest, Ekaterina; Silva-Franco, Fátima; Soanes, Darren; Syed, Khajamohiddin; Tagua, Víctor G.; Talbot, Nicholas J.; Thon, Michael R.; Tice, Hope; de Vries, Ronald P.; Wiebenga, Ad; Yadav, Jagjit S.; Braun, Edward L.; Baker, Scott E.; Garre, Victoriano; Schmutz, Jeremy; Horwitz, Benjamin A.; Torres-Martínez, Santiago; Idnurm, Alexander; Herrera-Estrella, Alfredo; Gabaldón, Toni; Grigoriev, Igor V.

2016-01-01

Summary Plants and fungi use light and other signals to regulate development, growth, and metabolism. The fruiting bodies of the fungus Phycomyces blakesleeanus are single cells that react to environmental cues, including light, but the mechanisms are largely unknown [1]. The related fungus Mucor circinelloides is an opportunistic human pathogen that changes its mode of growth upon receipt of signals from the environment to facilitate pathogenesis [2]. Understanding how these organisms respond to environmental cues should provide insights into the mechanisms of sensory perception and signal transduction by a single eukaryotic cell, and their role in pathogenesis. We sequenced the genomes of P. blakesleeanus and M. circinelloides, and show that they have been shaped by an extensive genome duplication or, most likely, a whole genome duplication (WGD), which is rarely observed in fungi [3-6]. We show that the genome duplication has expanded gene families, including those involved in signal transduction, and that duplicated genes have specialized, as evidenced by differences in their regulation by light. The transcriptional response to light varies with the developmental stage and is still observed in a photoreceptor mutant of P. blakesleeanus. A phototropic mutant of P. blakesleeanus with a heterozygous mutation in the photoreceptor gene madA demonstrates that photosensor dosage is important for the magnitude of signal transduction. We conclude that the genome duplication provided the means to improve signal transduction for enhanced perception of environmental signals. Our results will help to understand the role of genome dynamics in the evolution of sensory perception in eukaryotes. PMID:27238284

No Evidence for Ionotropic Pheromone Transduction in the Hawkmoth Manduca sexta.

PubMed

Nolte, Andreas; Gawalek, Petra; Koerte, Sarah; Wei, HongYing; Schumann, Robin; Werckenthin, Achim; Krieger, Jürgen; Stengl, Monika

2016-01-01

Insect odorant receptors (ORs) are 7-transmembrane receptors with inverse membrane topology. They associate with the conserved ion channel Orco. As chaperon, Orco maintains ORs in cilia and, as pacemaker channel, Orco controls spontaneous activity in olfactory receptor neurons. Odorant binding to ORs opens OR-Orco receptor ion channel complexes in heterologous expression systems. It is unknown, whether this also occurs in vivo. As an alternative to this ionotropic transduction, experimental evidence is accumulating for metabotropic odor transduction, implicating that insect ORs couple to G-proteins. Resulting second messengers gate various ion channels. They generate the sensillum potential that elicits phasic-tonic action potentials (APs) followed by late, long-lasting pheromone responses. Because it is still unclear how and when Orco opens after odor-OR-binding, we used tip recordings to examine in vivo the effects of the Orco antagonist OLC15 and the amilorides MIA and HMA on bombykal transduction in the hawkmoth Manduca sexta. In contrast to OLC15 both amilorides decreased the pheromone-dependent sensillum potential amplitude and the frequency of the phasic AP response. Instead, OLC15 decreased spontaneous activity, increased latencies of phasic-, and decreased frequencies of late, long-lasting pheromone responses Zeitgebertime-dependently. Our results suggest no involvement for Orco in the primary transduction events, in contrast to amiloride-sensitive channels. Instead of an odor-gated ionotropic receptor, Orco rather acts as a voltage- and apparently second messenger-gated pacemaker channel controlling the membrane potential and hence threshold and kinetics of the pheromone response.

Compact, high power, energy efficient transmit systems for UUVs using single crystal transducers

NASA Astrophysics Data System (ADS)

Robinson, Harold

2004-05-01

UUVs are currently being designed to perform a multiplitude of tasks in ocean exploration and Naval warfighting. Many of these tasks require the use of active acoustic projectors, and many may require the UUV to operate independently for hours, days, or even weeks. In order for a UUV to be as versatile as possible, its active transmit system must be versatile as well, implying that broad acoustic bandwidths are a must. However, due to size and battery life limitations, this broadband system must also be compact and energy efficient. By virtue of their extraordinary material properties, ferroelectric single crystals are the ideal transduction material for developing such broadband systems. The effect of their high coupling factor on transmit systems shall be illustrated by showing the dramatic impact on amplifier size, power factor, and acoustic response that is possible using these materials. In particular, a transducer built with these materials can be well matched to the power amplifier, i.e., 80% or more of the amplifier power reaches the transducer, over decades of frequency. Measured results from several prototype single crystal transducers shall be presented to demonstrate that the theoretical gains are actually realizable in practical devices. [Work sponsored by DARPA.

A multifunctional material based on co-electrospinning for developing biosensors with optical oxygen transduction.

PubMed

Ramon-Marquez, Teresa; Medina-Castillo, Antonio L; Nagiah, Naveen; Fernandez-Gutierrez, Alberto; Fernandez-Sanchez, Jorge F

2018-07-26

A multifunctional material based on co-electrospinning has been developed as a basic material for the development of biosensors with optical oxygen transduction. It is based on coaxial nanofibres: inner fibres containing an oxygen sensitive dye and outer fibres containing aldehyde groups to allow the formation of Schiff bases with the amino groups of the enzyme. The resulting material preserves the oxygen sensing properties of the inner optical transducer as well as exhibits a high capacity for immobilizing molecules on its surface. Uricase has been selected as model enzyme and several parameters (temperature, pH, reaction time, buffer, and enzyme concentration) have been optimised to demonstrate the versatility of this novel multifunctional material in the development of biosensors with optical oxygen transduction for determining uric acid in serum samples. It suggests that the proposed multifunctional material can provide a promising multifunctional platform for biosensing applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Adenoviral transduction supports matrix expression of alginate cultured articular chondrocytes.

PubMed

Pohle, D; Kasch, R; Herlyn, P; Bader, R; Mittlmeier, T; Pützer, B M; Müller-Hilke, B

2012-09-01

The present study examines the effects of adenoviral (Ad) transduction of human primary chondrocyte on transgene expression and matrix production. Primary chondrocytes were isolated from healthy articular cartilage and from cartilage with mild osteoarthritis (OA), transduced with an Ad vector and either immediately cultured in alginate or expanded in monolayer before alginate culture. Proteoglycan production was measured using dimethylmethylene blue (DMMB) assay and matrix gene expression was quantified by real-time PCR. Viral infection of primary chondrocytes results in a stable long time transgene expression for up to 13 weeks. Ad transduction does not significantly alter gene expression and matrix production if chondrocytes are immediately embedded in alginate. However, if expanded prior to three dimension (3D) culture in alginate, chondrocytes produce not only more proteoglycans compared to non-transduced controls, but also display an increased anabolic and decreased catabolic activity compared to non-transduced controls. We therefore suggest that successful autologous chondrocyte transplantation (ACT) should combine adenoviral transduction of primary chondrocytes with expansion in monolayer followed by 3D culture. Future studies will be needed to investigate whether the subsequent matrix production can be further improved by using Ad vectors bearing genes encoding matrix proteins. Copyright © 2012 Wiley Periodicals, Inc.

Transduction channels' gating can control friction on vibrating hair-cell bundles in the ear.

PubMed

Bormuth, Volker; Barral, Jérémie; Joanny, Jean-François; Jülicher, Frank; Martin, Pascal

2014-05-20

Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. Friction is generally thought to result mainly from viscous drag by the surrounding fluid. We demonstrate here that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle. We characterized friction by analyzing hysteresis in the force-displacement relation of single hair-cell bundles in response to periodic triangular stimuli. For bundle velocities high enough to outrun adaptation, we found that frictional forces were maximal within the narrow region of deflections that elicited significant channel gating, plummeted upon application of a channel blocker, and displayed a sublinear growth for increasing bundle velocity. At low velocity, the slope of the relation between the frictional force and velocity was nearly fivefold larger than the hydrodynamic friction coefficient that was measured when the transduction machinery was decoupled from bundle motion by severing tip links. A theoretical analysis reveals that channel friction arises from coupling the dynamics of the conformational change associated with channel gating to tip-link tension. Varying channel properties affects friction, with faster channels producing smaller friction. We propose that this intrinsic source of friction may contribute to the process that sets the hair cell's characteristic frequency of responsiveness.

Activity Dependent Signal Transduction in Skeletal Muscle

NASA Technical Reports Server (NTRS)

Hamilton, Susan L.

1999-01-01

The overall goals of this project are: 1) to define the initial signal transduction events whereby the removal of gravitational load from antigravity muscles, such as the soleus, triggers muscle atrophy, and 2) to develop countermeasures to prevent this from happening. Our rationale for this approach is that, if countermeasures can be developed to regulate these early events, we could avoid having to deal with the multiple cascades of events that occur downstream from the initial event. One of our major findings is that hind limb suspension causes an early and sustained increase in intracellular Ca(2+) concentration ([Ca (2+)](sub i)). In most cells the consequences of changes in ([Ca (2+)](sub i))depend on the amplitude, frequency and duration of the Ca(2+) signal and on other factors in the intracellular environment. We propose that muscle remodeling in microgravity represents a change in the balance among several CA(2+) regulated signal transduction pathways, in particular those involving the transcription factors NFAT and NFkB and the pro-apoptotic protein BAD. Other Ca(2+) sensitive pathways involving PKC, ras, rac, and CaM kinase II may also contribute to muscle remodeling.

High efficiency, long life terrestrial solar panel

NASA Technical Reports Server (NTRS)

Chao, T.; Khemthong, S.; Ling, R.; Olah, S.

1977-01-01

The design of a high efficiency, long life terrestrial module was completed. It utilized 256 rectangular, high efficiency solar cells to achieve high packing density and electrical output. Tooling for the fabrication of solar cells was in house and evaluation of the cell performance was begun. Based on the power output analysis, the goal of a 13% efficiency module was achievable.

Manipulation of light signal transduction as a means of modifying fruit nutritional quality in tomato

PubMed Central

Liu, Yongsheng; Roof, Sherry; Ye, Zhibiao; Barry, Cornelius; van Tuinen, Ageeth; Vrebalov, Julia; Bowler, Chris; Giovannoni, Jim

2004-01-01

Fruit constitutes a major component of human diets, providing fiber, vitamins, and phytonutrients. Carotenoids are a major class of compounds found in many fruits, providing nutritional benefits as precursors to essential vitamins and as antioxidants. Although recent gene isolation efforts and metabolic engineering have primarily targeted genes involved in carotenoid biosynthesis, factors that regulate flux through the carotenoid pathway remain largely unknown. Characterization of the tomato high-pigment mutations (hp1 and hp2) suggests the manipulation of light signal transduction machinery may be an effective approach toward practical manipulation of plant carotenoids. We demonstrate here that hp1 alleles represent mutations in a tomato UV-DAMAGED DNA-BINDING PROTEIN 1 (DDB1) homolog. We further demonstrate that two tomato light signal transduction genes, LeHY5 and LeCOP1LIKE, are positive and negative regulators of fruit pigmentation, respectively. Down-regulated LeHY5 plants exhibit defects in light responses, including inhibited seedling photomorphogenesis, loss of thylakoid organization, and reduced carotenoid accumulation. In contrast, repression of LeCOP1LIKE expression results in plants with exaggerated photomorphogenesis, dark green leaves, and elevated fruit carotenoid levels. These results suggest genes encoding components of light signal transduction machinery also influence fruit pigmentation and represent genetic tools for manipulation of fruit quality and nutritional value. PMID:15178762

Double-stranded RNA innate immune response activation from long-term adeno-associated virus vector transduction.

PubMed

Shao, Wenwei; Earley, Lauriel F; Chai, Zheng; Chen, Xiaojing; Sun, Junjiang; He, Ting; Deng, Meng; Hirsch, Matthew L; Ting, Jenny; Samulski, R Jude; Li, Chengwen

2018-06-21

Data from clinical trials for hemophilia B using adeno-associated virus (AAV) vectors have demonstrated decreased transgenic coagulation factor IX (hFIX) expression 6-10 weeks after administration of a high vector dose. While it is likely that capsid-specific cytotoxic T lymphocytes eliminate vector-transduced hepatocytes, thereby resulting in decreased hFIX, this observation is not intuitively consistent with restored hFIX levels following prednisone application. Although the innate immune response is immediately activated following AAV vector infection via TLR pathways, no studies exist regarding the role of the innate immune response at later time points after AAV vector transduction. Herein, activation of the innate immune response in cell lines, primary human hepatocytes, and hepatocytes in a human chimeric mouse model was observed at later time points following AAV vector transduction. Mechanistic analysis demonstrated that the double-stranded RNA (dsRNA) sensor MDA5 was necessary for innate immune response activation and that transient knockdown of MDA5, or MAVS, decreased IFN-β expression while increasing transgene production in AAV-transduced cells. These results both highlight the role of the dsRNA-triggered innate immune response in therapeutic transgene expression at later time points following AAV transduction and facilitate the execution of effective strategies to block the dsRNA innate immune response in future clinical trials.

[Differentially expressed genes of cell signal transduction associated with benzene poisoning by cDNA microarray].

PubMed

Wang, Hong; Bi, Yongyi; Tao, Ning; Wang, Chunhong

2005-08-01

To detect the differential expression of cell signal transduction genes associated with benzene poisoning, and to explore the pathogenic mechanisms of blood system damage induced by benzene. Peripheral white blood cell gene expression profile of 7 benzene poisoning patients, including one aplastic anemia, was determined by cDNA microarray. Seven chips from normal workers were served as controls. Cluster analysis of gene expression profile was performed. Among the 4265 target genes, 176 genes associated with cell signal transduction were differentially expressed. 35 up-regulated genes including PTPRC, STAT4, IFITM1 etc were found in at least 6 pieces of microarray; 45 down-regulated genes including ARHB, PPP3CB, CDC37 etc were found in at least 5 pieces of microarray. cDNA microarray technology is an effective technique for screening the differentially expressed genes of cell signal transduction. Disorder in cell signal transduction may play certain role in the pathogenic mechanism of benzene poisoning.

High Efficiency, Clean Combustion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donald Stanton

2010-03-31

Energy use in trucks has been increasing at a faster rate than that of automobiles within the U.S. transportation sector. According to the Energy Information Administration (EIA) Annual Energy Outlook (AEO), a 23% increase in fuel consumption for the U.S. heavy duty truck segment is expected between 2009 to 2020. The heavy duty vehicle oil consumption is projected to grow between 2009 and 2050 while light duty vehicle (LDV) fuel consumption will eventually experience a decrease. By 2050, the oil consumption rate by LDVs is anticipated to decrease below 2009 levels due to CAFE standards and biofuel use. In contrast,more » the heavy duty oil consumption rate is anticipated to double. The increasing trend in oil consumption for heavy trucks is linked to the vitality, security, and growth of the U.S. economy. An essential part of a stable and vibrant U.S. economy is a productive U.S. trucking industry. Studies have shown that the U.S. gross domestic product (GDP) is strongly correlated to freight transport. Over 90% of all U.S. freight tonnage is transported by diesel power and over 75% is transported by trucks. Given the vital role that the trucking industry plays in the economy, improving the efficiency of the transportation of goods was a central focus of the Cummins High Efficient Clean Combustion (HECC) program. In a commercial vehicle, the diesel engine remains the largest source of fuel efficiency loss, but remains the greatest opportunity for fuel efficiency improvements. In addition to reducing oil consumption and the dependency on foreign oil, this project will mitigate the impact on the environment by meeting US EPA 2010 emissions regulations. Innovation is a key element in sustaining a U.S. trucking industry that is competitive in global markets. Unlike passenger vehicles, the trucking industry cannot simply downsize the vehicle and still transport the freight with improved efficiency. The truck manufacturing and supporting industries are faced with

Characteristics of High- and Low-Efficiency Hospitals.

PubMed

Rosko, Michael; Wong, Herbert S; Mutter, Ryan

2017-01-01

We compared performance, operating characteristics, and market environments of low- and high-efficiency hospitals in the 37 states that supplied inpatient data to the Healthcare Cost and Utilization Project from 2006 to 2010. Hospital cost-inefficiency estimates using stochastic frontier analysis were generated. Hospitals were then grouped into the 100 most- and 100 least-efficient hospitals for subsequent analysis. Compared with the least efficient hospitals, high-efficiency hospitals tended to have lower average costs, higher labor productivity, and higher profit margins. The most efficient hospitals tended to be nonteaching, investor-owned, and members of multihospital systems. Hospitals in the high-efficiency group were located in areas with lower health maintenance organization penetration and less competition, and they had a higher share of Medicaid and Medicare admissions. Results of the analysis suggest there are opportunities for public policies to support improved efficiency in the hospital sector.

A Prize-Collecting Steiner Tree Approach for Transduction Network Inference

NASA Astrophysics Data System (ADS)

Bailly-Bechet, Marc; Braunstein, Alfredo; Zecchina, Riccardo

Into the cell, information from the environment is mainly propagated via signaling pathways which form a transduction network. Here we propose a new algorithm to infer transduction networks from heterogeneous data, using both the protein interaction network and expression datasets. We formulate the inference problem as an optimization task, and develop a message-passing, probabilistic and distributed formalism to solve it. We apply our algorithm to the pheromone response in the baker’s yeast S. cerevisiae. We are able to find the backbone of the known structure of the MAPK cascade of pheromone response, validating our algorithm. More importantly, we make biological predictions about some proteins whose role could be at the interface between pheromone response and other cellular functions.

FIST: a sensory domain for diverse signal transduction pathways in prokaryotes and ubiquitin signaling in eukaryotes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borziak, Kirill; Jouline, Igor B

2007-01-01

Motivation: Sensory domains that are conserved among Bacteria, Archaea and Eucarya are important detectors of common signals detected by living cells. Due to their high sequence divergence, sensory domains are difficult to identify. We systematically look for novel sensory domains using sensitive profile-based searches initi-ated with regions of signal transduction proteins where no known domains can be identified by current domain models. Results: Using profile searches followed by multiple sequence alignment, structure prediction, and domain architecture analysis, we have identified a novel sensory domain termed FIST, which is present in signal transduction proteins from Bacteria, Archaea and Eucarya. Remote similaritymore » to a known ligand-binding fold and chromosomal proximity of FIST-encoding genes to those coding for proteins involved in amino acid metabolism and transport suggest that FIST domains bind small ligands, such as amino acids.« less

Mobile DNA in cancer. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes.

PubMed

Tubio, Jose M C; Li, Yilong; Ju, Young Seok; Martincorena, Inigo; Cooke, Susanna L; Tojo, Marta; Gundem, Gunes; Pipinikas, Christodoulos P; Zamora, Jorge; Raine, Keiran; Menzies, Andrew; Roman-Garcia, Pablo; Fullam, Anthony; Gerstung, Moritz; Shlien, Adam; Tarpey, Patrick S; Papaemmanuil, Elli; Knappskog, Stian; Van Loo, Peter; Ramakrishna, Manasa; Davies, Helen R; Marshall, John; Wedge, David C; Teague, Jon W; Butler, Adam P; Nik-Zainal, Serena; Alexandrov, Ludmil; Behjati, Sam; Yates, Lucy R; Bolli, Niccolo; Mudie, Laura; Hardy, Claire; Martin, Sancha; McLaren, Stuart; O'Meara, Sarah; Anderson, Elizabeth; Maddison, Mark; Gamble, Stephen; Foster, Christopher; Warren, Anne Y; Whitaker, Hayley; Brewer, Daniel; Eeles, Rosalind; Cooper, Colin; Neal, David; Lynch, Andy G; Visakorpi, Tapio; Isaacs, William B; Veer, Laura Van't; Caldas, Carlos; Desmedt, Christine; Sotiriou, Christos; Aparicio, Sam; Foekens, John A; Eyfjörd, Jórunn Erla; Lakhani, Sunil R; Thomas, Gilles; Myklebost, Ola; Span, Paul N; Børresen-Dale, Anne-Lise; Richardson, Andrea L; Van de Vijver, Marc; Vincent-Salomon, Anne; Van den Eynden, Gert G; Flanagan, Adrienne M; Futreal, P Andrew; Janes, Sam M; Bova, G Steven; Stratton, Michael R; McDermott, Ultan; Campbell, Peter J

2014-08-01

Long interspersed nuclear element-1 (L1) retrotransposons are mobile repetitive elements that are abundant in the human genome. L1 elements propagate through RNA intermediates. In the germ line, neighboring, nonrepetitive sequences are occasionally mobilized by the L1 machinery, a process called 3' transduction. Because 3' transductions are potentially mutagenic, we explored the extent to which they occur somatically during tumorigenesis. Studying cancer genomes from 244 patients, we found that tumors from 53% of the patients had somatic retrotranspositions, of which 24% were 3' transductions. Fingerprinting of donor L1s revealed that a handful of source L1 elements in a tumor can spawn from tens to hundreds of 3' transductions, which can themselves seed further retrotranspositions. The activity of individual L1 elements fluctuated during tumor evolution and correlated with L1 promoter hypomethylation. The 3' transductions disseminated genes, exons, and regulatory elements to new locations, most often to heterochromatic regions of the genome. Copyright © 2014, American Association for the Advancement of Science.

Dual-transduction-mode sensing approach for chemical detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Liang; Swensen, James S.

2012-11-01

Smart devices such as electronic nose have been developed for application in many fields like national security, defense, environmental regulation, health care, pipeline monitoring and food analysis. Despite a large array of individual sensors, these devices still lack the ability to identify a target at a very low concentration out of a mixture of odors, limited by a single type of transduction as the sensing response to distinguish one odor from another. Here, we propose a new sensor architecture empowering each individual sensor with multi-dimensional transduction signals. The resolving power of our proposed electronic nose is thereby multiplied by amore » set of different and independent variables which synergistically will provide a unique combined fingerprint for each analyte. We demonstrate this concept using a Light Emitting Organic Field-Effect Transistor (LEOFET). Sensing response has been observed on both electrical and optical output signals from a green LEOFET upon exposure to an explosive taggant, with optical signal exhibiting much higher sensitivity. This new sensor architecture opens a field of devices for smart detection of chemical and biological targets.« less

High efficiency laser-pumped emerald lasers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lai, S.T.

1987-09-25

Highly efficient laser operation has been achieved in emerald. In a quasi-cw laser-pumped emerald laser, 64% output slope efficiency has been measured at 768 nm, corresponding to a laser quantum yield of 76%. An output power of 1.6 W was reached at 3.6 W of pump power at 647.1 nm from a krypton laser, and was pump power limited. The emerald laser has a tuning range of 720 to 842 nm. The round trip loss excluding the excited state absorption (ESA) is 0.4%/cm. These results indicate the high laser efficiency and the high optical quality of the emerald attainable inmore » the present laser.« less

Altering the threshold of an excitable signal transduction network changes cell migratory modes.

PubMed

Miao, Yuchuan; Bhattacharya, Sayak; Edwards, Marc; Cai, Huaqing; Inoue, Takanari; Iglesias, Pablo A; Devreotes, Peter N

2017-04-01

The diverse migratory modes displayed by different cell types are generally believed to be idiosyncratic. Here we show that the migratory behaviour of Dictyostelium was switched from amoeboid to keratocyte-like and oscillatory modes by synthetically decreasing phosphatidylinositol-4,5-bisphosphate levels or increasing Ras/Rap-related activities. The perturbations at these key nodes of an excitable signal transduction network initiated a causal chain of events: the threshold for network activation was lowered, the speed and range of propagating waves of signal transduction activity increased, actin-driven cellular protrusions expanded and, consequently, the cell migratory mode transitions ensued. Conversely, innately keratocyte-like and oscillatory cells were promptly converted to amoeboid by inhibition of Ras effectors with restoration of directed migration. We use computational analysis to explain how thresholds control cell migration and discuss the architecture of the signal transduction network that gives rise to excitability.

High-efficiency cavity-dumped micro-chip Yb:YAG laser

NASA Astrophysics Data System (ADS)

Nishio, M.; Maruko, A.; Inoue, M.; Takama, M.; Matsubara, S.; Okunishi, H.; Kato, K.; Kyomoto, K.; Yoshida, T.; Shimabayashi, K.; Morioka, M.; Inayoshi, S.; Yamagata, S.; Kawato, S.

2014-09-01

High-efficiency cavity-dumped ytterbium-doped yttrium aluminum garnet (Yb:YAG) laser was developed. Although the high quantum efficiency of ytterbium-doped laser materials is appropriate for high-efficiency laser oscillation, the efficiency is decreased by their quasi-three/four laser natures. High gain operation by high intensity pumping is suitable for high efficiency oscillation on the quasi-three/four lasers without extremely low temperature cooling. In our group, highest efficiency oscillations for continuous wave, nanosecond to picosecond pulse lasers were achieved at room temperature by the high gain operation in which pump intensities were beyond 100 kW/cm2.

High efficiency solar panel /HESP/

NASA Technical Reports Server (NTRS)

Stella, P. M.; Gay, C.; Uno, F.; Scott-Monck, J.

1978-01-01

A family of high efficiency, weldable silicon solar cells, incorporating nearly every feature of advanced cell technology developed in the past four years, was produced and subjected to space qualification testing. This matrix contained both field and non-field cells ranging in thickness from 0.10 mm to 0.30 mm, and in base resistivity from nominal two to one hundred ohm-cm. Initial power outputs as high as 20 mW/sq cm (14.8% AM0 efficiency) were produced by certain cell types within the matrix.

High efficiency SPS klystron design

NASA Technical Reports Server (NTRS)

Nalos, E. J.

1980-01-01

The most likely compact configuration to realize both high efficiency and high gain (approx. 40 dB) is a 5-6 cavity design focused by an electromagnet. The basic klystron efficiency cannot be expected to exceed 70-75% without collector depression. It was estimated that the net benefit of a 5 stage collector over a 2 stage collector is between 1.5 and 3.5 kW per tube. A modulating anode is incorporated in the design to enable rapid shutoff of the beam current in case the r.f. drive should be removed.

Identification of a cardiac specific protein transduction domain by in vivo biopanning using a M13 phage peptide display library in mice.

PubMed

Zahid, Maliha; Phillips, Brett E; Albers, Sean M; Giannoukakis, Nick; Watkins, Simon C; Robbins, Paul D

2010-08-17

A peptide able to transduce cardiac tissue specifically, delivering cargoes to the heart, would be of significant therapeutic potential for delivery of small molecules, proteins and nucleic acids. In order to identify peptide(s) able to transduce heart tissue, biopanning was performed in cell culture and in vivo with a M13 phage peptide display library. A cardiomyoblast cell line, H9C2, was incubated with a M13 phage 12 amino acid peptide display library. Internalized phage was recovered, amplified and then subjected to a total of three rounds of in vivo biopanning where infectious phage was isolated from cardiac tissue following intravenous injection. After the third round, 60% of sequenced plaques carried the peptide sequence APWHLSSQYSRT, termed cardiac targeting peptide (CTP). We demonstrate that CTP was able to transduce cardiomyocytes functionally in culture in a concentration and cell-type dependent manner. Mice injected with CTP showed significant transduction of heart tissue with minimal uptake by lung and kidney capillaries, and no uptake in liver, skeletal muscle, spleen or brain. The level of heart transduction by CTP also was greater than with a cationic transduction domain. Biopanning using a peptide phage display library identified a peptide able to transduce heart tissue in vivo efficiently and specifically. CTP could be used to deliver therapeutic peptides, proteins and nucleic acid specifically to the heart.

Transduction channels’ gating can control friction on vibrating hair-cell bundles in the ear

PubMed Central

Bormuth, Volker; Barral, Jérémie; Joanny, Jean-François; Jülicher, Frank; Martin, Pascal

2014-01-01

Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. Friction is generally thought to result mainly from viscous drag by the surrounding fluid. We demonstrate here that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle. We characterized friction by analyzing hysteresis in the force–displacement relation of single hair-cell bundles in response to periodic triangular stimuli. For bundle velocities high enough to outrun adaptation, we found that frictional forces were maximal within the narrow region of deflections that elicited significant channel gating, plummeted upon application of a channel blocker, and displayed a sublinear growth for increasing bundle velocity. At low velocity, the slope of the relation between the frictional force and velocity was nearly fivefold larger than the hydrodynamic friction coefficient that was measured when the transduction machinery was decoupled from bundle motion by severing tip links. A theoretical analysis reveals that channel friction arises from coupling the dynamics of the conformational change associated with channel gating to tip-link tension. Varying channel properties affects friction, with faster channels producing smaller friction. We propose that this intrinsic source of friction may contribute to the process that sets the hair cell’s characteristic frequency of responsiveness. PMID:24799674

Establishment of a universal and rational gene detection strategy through three-way junction-based remote transduction.

PubMed

Tang, Yidan; Lu, Baiyang; Zhu, Zhentong; Li, Bingling

2018-01-21

The polymerase chain reaction and many isothermal amplifications are able to achieve super gene amplification. Unfortunately, most commonly-used transduction methods, such as dye staining and Taqman-like probing, still suffer from shortcomings including false signals or difficult probe design, or are incompatible with multi-analysis. Here a universal and rational gene detection strategy has been established by translating isothermal amplicons to enzyme-free strand displacement circuits via three-way junction-based remote transduction. An assistant transduction probe was imported to form a partial hybrid with the target single-stranded nucleic acid. After systematic optimization the hybrid could serve as an associative trigger to activate a downstream circuit detector via a strand displacement reaction across the three-way junction. By doing so, the detection selectivity can be double-guaranteed through both amplicon-transducer recognition and the amplicon-circuit reaction. A well-optimized circuit can be immediately applied to a new target detection through simply displacing only 10-12 nt on only one component, according to the target. More importantly, this property for the first time enables multi-analysis and logic-analysis in a single reaction, sharing a single fluorescence reporter. In an applicable model, trace amounts of Cronobacter and Enterobacteria genes have been clearly distinguished from samples with no bacteria or one bacterium, with ultra-high sensitivity and selectivity.

High-efficiency solid state power amplifier

NASA Technical Reports Server (NTRS)

Wallis, Robert E. (Inventor); Cheng, Sheng (Inventor)

2005-01-01

A high-efficiency solid state power amplifier (SSPA) for specific use in a spacecraft is provided. The SSPA has a mass of less than 850 g and includes two different X-band power amplifier sections, i.e., a lumped power amplifier with a single 11-W output and a distributed power amplifier with eight 2.75-W outputs. These two amplifier sections provide output power that is scalable from 11 to 15 watts without major design changes. Five different hybrid microcircuits, including high-efficiency Heterostructure Field Effect Transistor (HFET) amplifiers and Monolithic Microwave Integrated Circuit (MMIC) phase shifters have been developed for use within the SSPA. A highly efficient packaging approach enables the integration of a large number of hybrid circuits into the SSPA.

Peptide Transduction-Based Therapies for Prostate Cancer

DTIC Science & Technology

2004-06-01

using an M13 peptide phage display library. Initial screening of the library for transduction of tumors in vivo has identified peptides able to...marker conjugates may have to be tested. (Months 6-12, Year 1) Progress: These experiments have been initiated. Task 4. An M13 peptide phage display ... phage 12 amino acid control peptide display library (New England Biolabs, Beverly, MA ) was used. Briefly, One nude mouse bearing a human tumor line

Protein Transduction Based Therapies for Breast Cancer

DTIC Science & Technology

2006-07-01

we also have developed a method for screening for tissue-targeted transduction peptides using an M13 peptide phage display library. Using this...Instead the focus was on the ability to identify a tumor specific peptide. Task 4. An M13 peptide phage display library will be used for...cancespecific tumor lines by screening a peptide phage display library both in cell culture as well as in nude micebearing xenografts. Initial results in

Maxwell's demon in biochemical signal transduction with feedback loop

PubMed Central

Ito, Sosuke; Sagawa, Takahiro

2015-01-01

Signal transduction in living cells is vital to maintain life itself, where information transfer in noisy environment plays a significant role. In a rather different context, the recent intensive research on ‘Maxwell's demon'—a feedback controller that utilizes information of individual molecules—have led to a unified theory of information and thermodynamics. Here we combine these two streams of research, and show that the second law of thermodynamics with information reveals the fundamental limit of the robustness of signal transduction against environmental fluctuations. Especially, we find that the degree of robustness is quantitatively characterized by an informational quantity called transfer entropy. Our information-thermodynamic approach is applicable to biological communication inside cells, in which there is no explicit channel coding in contrast to artificial communication. Our result could open up a novel biophysical approach to understand information processing in living systems on the basis of the fundamental information–thermodynamics link. PMID:26099556

Blood-brain barrier shuttle peptides enhance AAV transduction in the brain after systemic administration.

PubMed

Zhang, Xintao; He, Ting; Chai, Zheng; Samulski, R Jude; Li, Chengwen

2018-09-01

The adeno-associated virus (AAV) vector has been used in preclinical and clinical trials of gene therapy for central nervous system (CNS) diseases. One of the biggest challenges of effectively delivering AAV to the brain is to surmount the blood-brain barrier (BBB). Herein, we identified several potential BBB shuttle peptides that significantly enhanced AAV8 transduction in the brain after a systemic administration, the best of which was the THR peptide. The enhancement of AAV8 brain transduction by THR is dose-dependent, and neurons are the primary THR targets. Mechanism studies revealed that THR directly bound to the AAV8 virion, increasing its ability to cross the endothelial cell barrier. Further experiments showed that binding of THR to the AAV virion did not interfere with AAV8 infection biology, and that THR competitively blocked transferrin from binding to AAV8. Taken together, our results demonstrate, for the first time, that BBB shuttle peptides are able to directly interact with AAV and increase the ability of the AAV vectors to cross the BBB for transduction enhancement in the brain. These results will shed important light on the potential applications of BBB shuttle peptides for enhancing brain transduction with systemic administration of AAV vectors. Copyright © 2018 Elsevier Ltd. All rights reserved.

In vivo transduction of primitive mobilized hematopoietic stem cells after intravenous injection of integrating adenovirus vectors

PubMed Central

Richter, Maximilian; Saydaminova, Kamola; Yumul, Roma; Krishnan, Rohini; Liu, Jing; Nagy, Eniko-Eva; Singh, Manvendra; Izsvák, Zsuzsanna; Cattaneo, Roberto; Uckert, Wolfgang; Palmer, Donna; Ng, Philip; Haworth, Kevin G.; Kiem, Hans-Peter; Ehrhardt, Anja; Papayannopoulou, Thalia

2016-01-01

Current protocols for hematopoietic stem/progenitor cell (HSPC) gene therapy, involving the transplantation of ex vivo genetically modified HSPCs are complex and not without risk for the patient. We developed a new approach for in vivo HSPC transduction that does not require myeloablation and transplantation. It involves subcutaneous injections of granulocyte-colony-stimulating factor/AMD3100 to mobilize HSPCs from the bone marrow (BM) into the peripheral blood stream and the IV injection of an integrating, helper-dependent adenovirus (HD-Ad5/35++) vector system. These vectors target CD46, a receptor that is uniformly expressed on HSPCs. We demonstrated in human CD46 transgenic mice and immunodeficient mice with engrafted human CD34+ cells that HSPCs transduced in the periphery home back to the BM where they stably express the transgene. In hCD46 transgenic mice, we showed that our in vivo HSPC transduction approach allows for the stable transduction of primitive HSPCs. Twenty weeks after in vivo transduction, green fluorescent protein (GFP) marking in BM HSPCs (Lin−Sca1+Kit− cells) in most of the mice was in the range of 5% to 10%. The percentage of GFP-expressing primitive HSPCs capable of forming multilineage progenitor colonies (colony-forming units [CFUs]) increased from 4% of all CFUs at week 4 to 16% at week 12, indicating transduction and expansion of long-term surviving HSPCs. Our approach was well tolerated, did not result in significant transduction of nonhematopoietic tissues, and was not associated with genotoxicty. The ability to stably genetically modify HSPCs without the need of myeloablative conditioning is relevant for a broader clinical application of gene therapy. PMID:27554082

High efficiency incandescent lighting

DOEpatents

Bermel, Peter; Ilic, Ognjen; Chan, Walker R.; Musabeyoglu, Ahmet; Cukierman, Aviv Ruben; Harradon, Michael Robert; Celanovic, Ivan; Soljacic, Marin

2014-09-02

Incandescent lighting structure. The structure includes a thermal emitter that can, but does not have to, include a first photonic crystal on its surface to tailor thermal emission coupled to, in a high-view-factor geometry, a second photonic filter selected to reflect infrared radiation back to the emitter while passing visible light. This structure is highly efficient as compared to standard incandescent light bulbs.

Widespread transduction of astrocytes and neurons in the mouse central nervous system after systemic delivery of a self-complementary AAV-PHP.B vector.

PubMed

Rincon, Melvin Y; de Vin, Filip; Duqué, Sandra I; Fripont, Shelly; Castaldo, Stephanie A; Bouhuijzen-Wenger, Jessica; Holt, Matthew G

2018-04-01

Until recently, adeno-associated virus 9 (AAV9) was considered the AAV serotype most effective in crossing the blood-brain barrier (BBB) and transducing cells of the central nervous system (CNS), following systemic injection. However, a newly engineered capsid, AAV-PHP.B, is reported to cross the BBB at even higher efficiency. We investigated how much we could boost CNS transgene expression by using AAV-PHP.B carrying a self-complementary (sc) genome. To allow comparison, 6 weeks old C57BL/6 mice received intravenous injections of scAAV2/9-GFP or scAAV2/PHP.B-GFP at equivalent doses. Three weeks postinjection, transgene expression was assessed in brain and spinal cord. We consistently observed more widespread CNS transduction and higher levels of transgene expression when using the scAAV2/PHP.B-GFP vector. In particular, we observed an unprecedented level of astrocyte transduction in the cortex, when using a ubiquitous CBA promoter. In comparison, neuronal transduction was much lower than previously reported. However, strong neuronal expression (including spinal motor neurons) was observed when the human synapsin promoter was used. These findings constitute the first reported use of an AAV-PHP.B capsid, encapsulating a scAAV genome, for gene transfer in adult mice. Our results underscore the potential of this AAV construct as a platform for safer and more efficacious gene therapy vectors for the CNS.

Resting lymphocyte transduction with measles virus glycoprotein pseudotyped lentiviral vectors relies on CD46 and SLAM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou Qi; Schneider, Irene C.; Gallet, Manuela

2011-05-10

The measles virus (MV) glycoproteins hemagglutinin (H) and fusion (F) were recently shown to mediate transduction of resting lymphocytes by lentiviral vectors. MV vaccine strains use CD46 or signaling lymphocyte activation molecule (SLAM) as receptor for cell entry. A panel of H protein mutants derived from vaccine strain or wild-type MVs that lost or gained CD46 or SLAM receptor usage were investigated for their ability to mediate gene transfer into unstimulated T lymphocytes. The results demonstrate that CD46 is sufficient for efficient vector particle association with unstimulated lymphocytes. For stable gene transfer into these cells, however, both MV receptors weremore » found to be essential.« less

High energy efficient solid state laser sources

NASA Technical Reports Server (NTRS)

Byer, Robert L.

1989-01-01

Recent progress in the development of highly efficient coherent optical sources was reviewed. This work has focused on nonlinear frequency conversion of the highly coherent output of the non-planar ring laser oscillators developed earlier in the program, and includes high efficiency second harmonic generation and the operation of optical parametric oscillators for wavelength diversity and tunability.

High energy efficient solid state laser sources

NASA Technical Reports Server (NTRS)

Byer, Robert L.

1988-01-01

Recent progress in the development of highly efficient coherent optical sources is reviewed. This work focusses on nonlinear frequency conversion of the highly coherent output of the Non-Planar Ring Laser Oscillators developed earlier in the program, and includes high efficiency second harmonic generation and the operation of optical parametric oscillators for wavelength diversity and tunability.

Cilia- and Flagella-Associated Protein 69 Regulates Olfactory Transduction Kinetics in Mice

PubMed Central

Dong, Frederick N.

2017-01-01

Animals detect odorous chemicals through specialized olfactory sensory neurons (OSNs) that transduce odorants into neural electrical signals. We identified a novel and evolutionarily conserved protein, cilia- and flagella-associated protein 69 (CFAP69), in mice that regulates olfactory transduction kinetics. In the olfactory epithelium, CFAP69 is enriched in OSN cilia, where olfactory transduction occurs. Bioinformatic analysis suggests that a large portion of CFAP69 can form Armadillo-type α-helical repeats, which may mediate protein–protein interactions. OSNs lacking CFAP69, remarkably, displayed faster kinetics in both the on and off phases of electrophysiological responses at both the neuronal ensemble level as observed by electroolfactogram and the single-cell level as observed by single-cell suction pipette recordings. In single-cell analysis, OSNs lacking CFAP69 showed faster response integration and were able to fire APs more faithfully to repeated odor stimuli. Furthermore, both male and female mutant mice that specifically lack CFAP69 in OSNs exhibited attenuated performance in a buried food pellet test when a background of the same odor to the food pellet was present even though they should have better temporal resolution of coding olfactory stimulation at the peripheral. Therefore, the role of CFAP69 in the olfactory system seems to be to allow the olfactory transduction machinery to work at a precisely regulated range of response kinetics for robust olfactory behavior. SIGNIFICANCE STATEMENT Sensory receptor cells are generally thought to evolve to respond to sensory cues as fast as they can. This idea is consistent with mutational analyses in various sensory systems, where mutations of sensory receptor cells often resulted in reduced response size and slowed response kinetics. Contrary to this idea, we have found that there is a kinetic “damper” present in the olfactory transduction cascade of the mouse that slows down the response kinetics and

Design of a Retrovirus-Derived Vector for Expression and Transduction of Exogenous Genes in Mammalian Cells

PubMed Central

Perkins, Archibald S.; Kirschmeier, Paul T.; Gattoni-Celli, Sebastiano; Weinstein, I. Bernard

1983-01-01

We have developed a transfection vector for animal cells that contains long terminal repeat (LTR) sequences to promote expression. Plasmid p101/101, a derivative of plasmid pBR322 containing the complete Moloney murine sarcoma virus genome, was cut with restriction enzymes and religated so that both the 5′ and 3′ LTRs were retained and all but about 700 base pairs of the intervening viral sequences were removed. To test this vector, the Escherichia coli gene gpt was cloned into a unique PstI site, between the two LTRs, with guanine and cytosine tailing, a method that can be generalized for insertion of any DNA segment into this vector. When DNA from recombinant plasmids in which the gpt gene was inserted in the same transcriptional polarity as the LTR sequences was transfected onto murine or rat fibroblast cultures, we obtained a high yield of Gpt+ colonies. However, plasmid constructs with the gpt gene in the opposite polarity were virtually devoid of activity. With gpt in the proper orientation, restriction enzyme cuts within the LTRs or between the 5′ LTR and the gpt gene reduced transfection by more than 98%, whereas a cut between the gpt gene and the 3′ LTR gave an 80% reduction in activity. Thus, both 5′ and 3′ LTR sequences are essential for optimal gpt expression, although the 5′ LTR appears to play a more important role. When the LTR-gpt plasmid was transfected onto murine leukemia virus-infected mouse fibroblasts, we obtained evidence that RNA copies became pseudotyped into viral particles which could transfer the Gpt+ phenotype into rodent cells with extremely high efficiency. This vector should prove useful for high-efficiency transduction of a variety of genes in mammalian cells. Images PMID:6308426

Calcium and signal transduction in plants

NASA Technical Reports Server (NTRS)

Poovaiah, B. W.; Reddy, A. S.

1993-01-01

Environmental and hormonal signals control diverse physiological processes in plants. The mechanisms by which plant cells perceive and transduce these signals are poorly understood. Understanding biochemical and molecular events involved in signal transduction pathways has become one of the most active areas of plant research. Research during the last 15 years has established that Ca2+ acts as a messenger in transducing external signals. The evidence in support of Ca2+ as a messenger is unequivocal and fulfills all the requirements of a messenger. The role of Ca2+ becomes even more important because it is the only messenger known so far in plants. Since our last review on the Ca2+ messenger system in 1987, there has been tremendous progress in elucidating various aspects of Ca(2+) -signaling pathways in plants. These include demonstration of signal-induced changes in cytosolic Ca2+, calmodulin and calmodulin-like proteins, identification of different Ca2+ channels, characterization of Ca(2+) -dependent protein kinases (CDPKs) both at the biochemical and molecular levels, evidence for the presence of calmodulin-dependent protein kinases, and increased evidence in support of the role of inositol phospholipids in the Ca(2+) -signaling system. Despite the progress in Ca2+ research in plants, it is still in its infancy and much more needs to be done to understand the precise mechanisms by which Ca2+ regulates a wide variety of physiological processes. The purpose of this review is to summarize some of these recent developments in Ca2+ research as it relates to signal transduction in plants.

Transductive multi-view zero-shot learning.

PubMed

Fu, Yanwei; Hospedales, Timothy M; Xiang, Tao; Gong, Shaogang

2015-11-01

Most existing zero-shot learning approaches exploit transfer learning via an intermediate semantic representation shared between an annotated auxiliary dataset and a target dataset with different classes and no annotation. A projection from a low-level feature space to the semantic representation space is learned from the auxiliary dataset and applied without adaptation to the target dataset. In this paper we identify two inherent limitations with these approaches. First, due to having disjoint and potentially unrelated classes, the projection functions learned from the auxiliary dataset/domain are biased when applied directly to the target dataset/domain. We call this problem the projection domain shift problem and propose a novel framework, transductive multi-view embedding, to solve it. The second limitation is the prototype sparsity problem which refers to the fact that for each target class, only a single prototype is available for zero-shot learning given a semantic representation. To overcome this problem, a novel heterogeneous multi-view hypergraph label propagation method is formulated for zero-shot learning in the transductive embedding space. It effectively exploits the complementary information offered by different semantic representations and takes advantage of the manifold structures of multiple representation spaces in a coherent manner. We demonstrate through extensive experiments that the proposed approach (1) rectifies the projection shift between the auxiliary and target domains, (2) exploits the complementarity of multiple semantic representations, (3) significantly outperforms existing methods for both zero-shot and N-shot recognition on three image and video benchmark datasets, and (4) enables novel cross-view annotation tasks.

Highly Efficient Nondoped Green Organic Light-Emitting Diodes with Combination of High Photoluminescence and High Exciton Utilization.

PubMed

Wang, Chu; Li, Xianglong; Pan, Yuyu; Zhang, Shitong; Yao, Liang; Bai, Qing; Li, Weijun; Lu, Ping; Yang, Bing; Su, Shijian; Ma, Yuguang

2016-02-10

Photoluminescence (PL) efficiency and exciton utilization efficiency are two key parameters to harvest high-efficiency electroluminescence (EL) in organic light-emitting diodes (OLEDs). But it is not easy to simultaneously combine these two characteristics (high PL efficiency and high exciton utilization) into a fluorescent material. In this work, an efficient combination was achieved through two concepts of hybridized local and charge-transfer (CT) state (HLCT) and "hot exciton", in which the former is responsible for high PL efficiency while the latter contributes to high exciton utilization. On the basis of a tiny chemical modification in TPA-BZP, a green-light donor-acceptor molecule, we designed and synthesized CzP-BZP with this efficeient combination of high PL efficiency of η(PL) = 75% in the solid state and maximal exciton utilization efficiency up to 48% (especially, the internal quantum efficiency of η(IQE) = 35% substantially exceed 25% of spin statistics limit) in OLED. The nondoped OLED of CzP-BZP exhibited an excellent performance: a green emission with a CIE coordinate of (0.34, 0.60), a maximum current efficiency of 23.99 cd A(-1), and a maximum external quantum efficiency (EQE, η(EQE)) of 6.95%. This combined HLCT state and "hot exciton" strategy should be a practical way to design next-generation, low-cost, high-efficiency fluorescent OLED materials.

Interferon-α Silencing by Small Interference RNA Increases Adenovirus Transduction and Transgene Expression in Huh7 Cells.

PubMed

Sobrevilla-Navarro, Ana Alondra; Sandoval-Rodríguez, Ana; García-Bañuelos, Jesús Javier; Armendariz-Borunda, Juan; Salazar-Montes, Adriana María

2018-04-01

Adenoviruses are the most common vectors used in clinical trials of gene therapy. In 2017, 21.2% of clinical trials used rAds as vectors. Systemic administration of rAds results in high tropism in the liver. Interferon types α and β are the major antiviral cytokines which orchestrate the host's immune response against rAd, limiting therapeutic gene expression and preventing subsequent vector administration. siRNA is small double-strand RNAs that temporally inhibit the expression of a specific gene. The aim is to evaluate the effect of IFN-α blocking by a specific siRNA on Ad-GFP transduction and on transgene expression in Huh7 cells in culture. Huh7 cells were cultured in DMEM and transfected with 70 nM of siRNA-IFN-α. Six hours later, the cells were exposed to 1 × 10 9  vp/ml of rAd-GFP for 24 h. Expression of IFN-α, TNF-α and the PKR gene was determined by RT-qPCR. Percentage of transduction was analyzed by flow cytometry and by qPCR. GFP expression was determined by western blot. 70 nM of siRNA-IFN-α inhibited 96% of IFN-α and 65% of TNF-α gene expression compared to an irrelevant siRNA. Percentage of transduction and transgene expression increased in these cells compared to an irrelevant siRNA. Inhibition of IFN-α expression by siRNA-IFN-α enabled a higher level of transduction and transgene expression GFP, highlighting the role of IFN-α in the elimination of adenovirus in transduced cells and thus suggesting that its inhibition could be an important strategy for gene therapy in clinical trials using adenovirus as a vector directed to liver diseases.

Enabling High Efficiency Ethanol Engines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szybist, J.; Confer, K.

2011-03-01

Delphi Automotive Systems and ORNL established this CRADA to explore the potential to improve the energy efficiency of spark-ignited engines operating on ethanol-gasoline blends. By taking advantage of the fuel properties of ethanol, such as high compression ratio and high latent heat of vaporization, it is possible to increase efficiency with ethanol blends. Increasing the efficiency with ethanol-containing blends aims to remove a market barrier of reduced fuel economy with E85 fuel blends, which is currently about 30% lower than with petroleum-derived gasoline. The same or higher engine efficiency is achieved with E85, and the reduction in fuel economy ismore » due to the lower energy density of E85. By making ethanol-blends more efficient, the fuel economy gap between gasoline and E85 can be reduced. In the partnership between Delphi and ORNL, each organization brought a unique and complementary set of skills to the project. Delphi has extensive knowledge and experience in powertrain components and subsystems as well as overcoming real-world implementation barriers. ORNL has extensive knowledge and expertise in non-traditional fuels and improving engine system efficiency for the next generation of internal combustion engines. Partnering to combine these knowledge bases was essential towards making progress to reducing the fuel economy gap between gasoline and E85. ORNL and Delphi maintained strong collaboration throughout the project. Meetings were held regularly, usually on a bi-weekly basis, with additional reports, presentations, and meetings as necessary to maintain progress. Delphi provided substantial hardware support to the project by providing components for the single-cylinder engine experiments, engineering support for hardware modifications, guidance for operational strategies on engine research, and hardware support by providing a flexible multi-cylinder engine to be used for optimizing engine efficiency with ethanol-containing fuels.« less

Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems

PubMed Central

Chan, Ken Y; Jang, Min J; Yoo, Bryan B; Greenbaum, Alon; Ravi, Namita; Wu, Wei-Li; Sánchez-Guardado, Luis; Lois, Carlos; Mazmanian, Sarkis K; Deverman, Benjamin E; Gradinaru, Viviana

2017-01-01

Adeno-associated viruses (AAVs) are commonly used for in vivo gene transfer. Nevertheless, AAVs that provide efficient transduction across specific organs or cell populations are needed. Here, we describe AAV-PHP.eB and AAV-PHP.S, capsids that efficiently transduce the central and peripheral nervous systems, respectively. In the adult mouse, intravenous administration of 1×1011 vector genomes (vg) of AAV-PHP.eB transduced 69% of cortical and 55% of striatal neurons, while 1×1012 vg AAV-PHP.S transduced 82% of dorsal root ganglion neurons, as well as cardiac and enteric neurons. The efficiency of these vectors facilitates robust co-transduction and stochastic, multicolor labeling for individual cell morphology studies. To support such efforts, we provide methods for labeling a tunable fraction of cells without compromising color diversity. Furthermore, when used with cell type-specific promoters, these AAVs provide targeted gene expression across the nervous system and enable efficient and versatile gene manipulation throughout the nervous system of transgenic and non-transgenic animals. PMID:28671695

Jaagsiekte Sheep Retrovirus Envelope Efficiently Pseudotypes Human Immunodeficiency Virus Type 1-Based Lentiviral Vectors

PubMed Central

Liu, Shan-Lu; Halbert, Christine L.; Miller, A. Dusty

2004-01-01

Jaagsiekte sheep retrovirus (JSRV) infects lung epithelial cells in sheep, and oncoretroviral vectors bearing JSRV Env can mediate transduction of human cells, suggesting that such vectors might be useful for lung-directed gene therapy. Here we show that JSRV Env can also efficiently pseudotype a human immunodeficiency virus type 1-based lentiviral vector, a more suitable vector for transduction of slowly dividing lung epithelial cells. We created several chimeric Env proteins that, unlike the parental Env, do not transform rodent fibroblasts but are still capable of pseudotyping lentiviral and oncoretroviral vectors. PMID:14963173

Defining Specificity Determinants of cGMP Mediated Gustatory Sensory Transduction in Caenorhabditis elegans

PubMed Central

Smith, Heidi K.; Luo, Linjiao; O’Halloran, Damien; Guo, Dagang; Huang, Xin-Yun; Samuel, Aravinthan D. T.; Hobert, Oliver

2013-01-01

Cyclic guanosine monophosphate (cGMP) is a key secondary messenger used in signal transduction in various types of sensory neurons. The importance of cGMP in the ASE gustatory receptor neurons of the nematode Caenorhabditis elegans was deduced by the observation that multiple receptor-type guanylyl cyclases (rGCs), encoded by the gcy genes, and two presently known cyclic nucleotide-gated ion channel subunits, encoded by the tax-2 and tax-4 genes, are essential for ASE-mediated gustatory behavior. We describe here specific mechanistic features of cGMP-mediated signal transduction in the ASE neurons. First, we assess the specificity of the sensory functions of individual rGC proteins. We have previously shown that multiple rGC proteins are expressed in a left/right asymmetric manner in the functionally lateralized ASE neurons and are required to sense distinct salt cues. Through domain swap experiments among three different rGC proteins, we show here that the specificity of individual rGC proteins lies in their extracellular domains and not in their intracellular, signal-transducing domains. Furthermore, we find that rGC proteins are also sufficient to confer salt sensory responses to other neurons. Both findings support the hypothesis that rGC proteins are salt receptor proteins. Second, we identify a novel, likely downstream effector of the rGC proteins in gustatory signal transduction, a previously uncharacterized cyclic nucleotide-gated (CNG) ion channel, encoded by the che-6 locus. che-6 mutants show defects in gustatory sensory transduction that are similar to defects observed in animals lacking the tax-2 and tax-4 CNG channels. In contrast, thermosensory signal transduction, which also requires tax-2 and tax-4, does not require che-6, but requires another CNG, cng-3. We propose that CHE-6 may form together with two other CNG subunits, TAX-2 and TAX-4, a gustatory neuron-specific heteromeric CNG channel complex. PMID:23695300

Electrokinetic Transduction of Acoustic Waves In Ocean Sediments

DTIC Science & Technology

2002-09-30

acoustic —motion in ocean sediments. The Biot theory of poroelastic media captures much of the sediment physics left out by other models [2]. It fits...in subsurface acoustical imaging, Mine Counter- Measures, and Anti-Submarine Warfare. To obtain essential experimental data to support the modeling ...Electrokinetic Transduction of Acoustic Waves In Ocean Sediments Gareth I. Block Applied Research Laboratories, U.T. Austin P.O. Box 8029

The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis

PubMed Central

Smith, Gina A.; Fearnley, Gareth W.; Tomlinson, Darren C.; Harrison, Michael A.; Ponnambalam, Sreenivasan

2015-01-01

VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR–VEGF complexes with membrane trafficking along the endosome–lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR–VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments. PMID:26285805

Requirements for high-efficiency solar cells

NASA Technical Reports Server (NTRS)

Sah, C. T.

1986-01-01

Minimum recombination and low injection level are essential for high efficiency. Twenty percent AM1 efficiency requires a dark recombination current density of 2 x 10 to the minus 13th power A/sq cm and a recombination center density of less than 10 to the 10th power /cu cm. Recombination mechanisms at thirteen locations in a conventional single crystalline silicon cell design are reviewed. Three additional recombination locations are described at grain boundaries in polycrystalline cells. Material perfection and fabrication process optimization requirements for high efficiency are outlined. Innovative device designs to reduce recombination in the bulk and interfaces of single crystalline cells and in the grain boundary of polycrystalline cells are reviewed.

Presence of Ca2+-dependent K+ channels in chemosensory cilia support a role in odor transduction.

PubMed

Delgado, Ricardo; Saavedra, M Veronica; Schmachtenberg, Oliver; Sierralta, Jimena; Bacigalupo, Juan

2003-09-01

Olfactory receptor neurons (ORNs) respond to odorants with changes in the action potential firing rate. Excitatory responses, consisting of firing increases, are mediated by a cyclic AMP cascade that leads to the activation of cationic nonselective cyclic nucleotide-gated (CNG) channels and Ca2+-dependent Cl- (ClCa) channels. This process takes place in the olfactory cilia, where all protein components of this cascade are confined. ORNs from various vertebrate species have also been shown to generate inhibitory odor responses, expressed as decreases in action potential discharges. Odor inhibition appears to rely on Ca2+-dependent K+ (KCa) channels, but the underlying transduction mechanism remains unknown. If these channels are involved in odor transduction, they are expected to be present in the olfactory cilia. We found that a specific antibody against a large conductance KCa recognized a protein of approximately 116 kDa in Western blots of purified rat olfactory ciliary membranes. Moreover, the antibody labeled ORN cilia in isolated ORNs from rat and toad (Caudiverbera caudiverbera). In addition, single-channel recordings from inside-out membrane patches excised from toad chemosensory cilia showed the presence of 4 different types of KCa channels, with unitary conductances of 210, 60, 12, and 29 and 60 pS, high K+-selectivity, and Ca2+ sensitivities in the low micromolar range. Our work demonstrates the presence of K+ channels in the ORN cilia and supports their participation in odor transduction.

Melanin, Radiation, and Energy Transduction in Fungi.

PubMed

Casadevall, Arturo; Cordero, Radames J B; Bryan, Ruth; Nosanchuk, Joshua; Dadachova, Ekaterina

2017-03-01

Melanin pigments are found in many diverse fungal species, where they serve a variety of functions that promote fitness and cell survival. Melanotic fungi inhabit some of the most extreme habitats on earth such as the damaged nuclear reactor at Chernobyl and the highlands of Antarctica, both of which are high-radiation environments. Melanotic fungi migrate toward radioactive sources, which appear to enhance their growth. This phenomenon, combined with the known capacities of melanin to absorb a broad spectrum of electromagnetic radiation and transduce this radiation into other forms of energy, raises the possibility that melanin also functions in harvesting such energy for biological usage. The ability of melanotic fungi to harness electromagnetic radiation for physiological processes has enormous implications for biological energy flows in the biosphere and for exobiology, since it provides new mechanisms for survival in extraterrestrial conditions. Whereas some features of the way melanin-related energy transduction works can be discerned by linking various observations and circumstantial data, the mechanistic details remain to be discovered.

Excitation and Adaptation in Bacteria–a Model Signal Transduction System that Controls Taxis and Spatial Pattern Formation

PubMed Central

Othmer, Hans G.; Xin, Xiangrong; Xue, Chuan

2013-01-01

The machinery for transduction of chemotactic stimuli in the bacterium E. coli is one of the most completely characterized signal transduction systems, and because of its relative simplicity, quantitative analysis of this system is possible. Here we discuss models which reproduce many of the important behaviors of the system. The important characteristics of the signal transduction system are excitation and adaptation, and the latter implies that the transduction system can function as a “derivative sensor” with respect to the ligand concentration in that the DC component of a signal is ultimately ignored if it is not too large. This temporal sensing mechanism provides the bacterium with a memory of its passage through spatially- or temporally-varying signal fields, and adaptation is essential for successful chemotaxis. We also discuss some of the spatial patterns observed in populations and indicate how cell-level behavior can be embedded in population-level descriptions. PMID:23624608

Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma.

PubMed

Ge, Xuecai; Milenkovic, Ljiljana; Suyama, Kaye; Hartl, Tom; Purzner, Teresa; Winans, Amy; Meyer, Tobias; Scott, Matthew P

2015-09-15

Alterations in Hedgehog (Hh) signaling lead to birth defects and cancers including medulloblastoma, the most common pediatric brain tumor. Although inhibitors targeting the membrane protein Smoothened suppress Hh signaling, acquired drug resistance and tumor relapse call for additional therapeutic targets. Here we show that phosphodiesterase 4D (PDE4D) acts downstream of Neuropilins to control Hh transduction and medulloblastoma growth. PDE4D interacts directly with Neuropilins, positive regulators of Hh pathway. The Neuropilin ligand Semaphorin3 enhances this interaction, promoting PDE4D translocation to the plasma membrane and cAMP degradation. The consequent inhibition of protein kinase A (PKA) enhances Hh transduction. In the developing cerebellum, genetic removal of Neuropilins reduces Hh signaling activity and suppresses proliferation of granule neuron precursors. In mouse medulloblastoma allografts, PDE4D inhibitors suppress Hh transduction and inhibit tumor growth. Our findings reveal a new regulatory mechanism of Hh transduction, and highlight PDE4D as a promising target to treat Hh-related tumors.

Genetic Analysis of Gravity Signal Transduction in Arabidopsis Roots

NASA Astrophysics Data System (ADS)

Masson, Patrick; Strohm, Allison; Barker, Richard; Su, Shih-Heng

Like most other plant organs, roots use gravity as a directional guide for growth. Specialized cells within the columella region of the root cap (the statocytes) sense the direction of gravity through the sedimentation of starch-filled plastids (amyloplasts). Amyloplast movement and/or pressure on sensitive membranes triggers a gravity signal transduction pathway within these cells, which leads to a fast transcytotic relocalization of plasma-membrane associated auxin-efflux carrier proteins of the PIN family (PIN3 and PIN7) toward the bottom membrane. This leads to a polar transport of auxin toward the bottom flank of the cap. The resulting lateral auxin gradient is then transmitted toward the elongation zones where it triggers a curvature that ultimately leads to a restoration of vertical downward growth. Our laboratory is using strategies derived from genetics and systems biology to elucidate the molecular mechanisms that modulate gravity sensing and signal transduction in the columella cells of the root cap. Our previous research uncovered two J-domain-containing proteins, ARG1 and ARL2, as contributing to this process. Mutations in the corresponding paralogous genes led to alterations of root and hypocotyl gravitropism accompanied by an inability for the statocytes to develop a cytoplasmic alkalinization, relocalize PIN3, and transport auxin laterally, in response to gravistimulation. Both proteins are associated peripherally to membranes belonging to various compartments of the vesicular trafficking pathway, potentially modulating the trafficking of defined proteins between plasma membrane and endosomes. MAR1 and MAR2, on the other end, are distinct proteins of the plastidic outer envelope protein import TOC complex (the transmembrane channel TOC75 and the receptor TOC132, respectively). Mutations in the corresponding genes enhance the gravitropic defects of arg1. Using transformation-rescue experiments with truncated versions of TOC132 (MAR2), we have shown

Zinc-finger nuclease-mediated gene correction using single AAV vector transduction and enhancement by Food and Drug Administration-approved drugs

PubMed Central

Ellis, BL; Hirsch, ML; Porter, SN; Samulski, RJ; Porteus, MH

2016-01-01

An emerging strategy for the treatment of monogenic diseases uses genetic engineering to precisely correct the mutation(s) at the genome level. Recent advancements in this technology have demonstrated therapeutic levels of gene correction using a zinc-finger nuclease (ZFN)-induced DNA double-strand break in conjunction with an exogenous DNA donor substrate. This strategy requires efficient nucleic acid delivery and among viral vectors, recombinant adeno-associated virus (rAAV) has demonstrated clinical success without pathology. However, a major limitation of rAAV is the small DNA packaging capacity and to date, the use of rAAV for ZFN gene delivery has yet to be reported. Theoretically, an ideal situation is to deliver both ZFNs and the repair substrate in a single vector to avoid inefficient gene targeting and unwanted mutagenesis, both complications of a rAAV co-transduction strategy. Therefore, a rAAV format was generated in which a single polypeptide encodes the ZFN monomers connected by a ribosome skipping 2A peptide and furin cleavage sequence. On the basis of this arrangement, a DNA repair substrate of 750 nucleotides was also included in this vector. Efficient polypeptide processing to discrete ZFNs is demonstrated, as well as the ability of this single vector format to stimulate efficient gene targeting in a human cell line and mouse model derived fibroblasts. Additionally, we increased rAAV-mediated gene correction up to sixfold using a combination of Food and Drug Administration-approved drugs, which act at the level of AAV vector transduction. Collectively, these experiments demonstrate the ability to deliver ZFNs and a repair substrate by a single AAV vector and offer insights for the optimization of rAAV-mediated gene correction using drug therapy. PMID:22257934

Quantum Transduction with Adaptive Control

NASA Astrophysics Data System (ADS)

Zhang, Mengzhen; Zou, Chang-Ling; Jiang, Liang

2018-01-01

Quantum transducers play a crucial role in hybrid quantum networks. A good quantum transducer can faithfully convert quantum signals from one mode to another with minimum decoherence. Most investigations of quantum transduction are based on the protocol of direct mode conversion. However, the direct protocol requires the matching condition, which in practice is not always feasible. Here we propose an adaptive protocol for quantum transducers, which can convert quantum signals without requiring the matching condition. The adaptive protocol only consists of Gaussian operations, feasible in various physical platforms. Moreover, we show that the adaptive protocol can be robust against imperfections associated with finite squeezing, thermal noise, and homodyne detection, and it can be implemented to realize quantum state transfer between microwave and optical modes.

Quantum Transduction with Adaptive Control.

PubMed

Zhang, Mengzhen; Zou, Chang-Ling; Jiang, Liang

2018-01-12

Quantum transducers play a crucial role in hybrid quantum networks. A good quantum transducer can faithfully convert quantum signals from one mode to another with minimum decoherence. Most investigations of quantum transduction are based on the protocol of direct mode conversion. However, the direct protocol requires the matching condition, which in practice is not always feasible. Here we propose an adaptive protocol for quantum transducers, which can convert quantum signals without requiring the matching condition. The adaptive protocol only consists of Gaussian operations, feasible in various physical platforms. Moreover, we show that the adaptive protocol can be robust against imperfections associated with finite squeezing, thermal noise, and homodyne detection, and it can be implemented to realize quantum state transfer between microwave and optical modes.

IGF-1 signaling mediated cell-specific skeletal mechano-transduction.

PubMed

Tian, Faming; Wang, Yongmei; Bikle, Daniel D

2018-02-01

Mechanical loading preserves bone mass and stimulates bone formation, whereas skeletal unloading leads to bone loss. In addition to osteocytes, which are considered the primary sensor of mechanical load, osteoblasts, and bone specific mesenchymal stem cells also are involved. The skeletal response to mechanical signals is a complex process regulated by multiple signaling pathways including that of insulin-like growth factor-1 (IGF-1). Conditional osteocyte deletion of IGF-1 ablates the osteogenic response to mechanical loading. Similarly, osteocyte IGF-1 receptor (IGF-1R) expression is necessary for reloading-induced periosteal bone formation. Transgenic overexpression of IGF-1 in osteoblasts results in enhanced responsiveness to in vivo mechanical loading in mice, a response which is eliminated by osteoblastic conditional disruption of IGF-1 in vivo. Bone marrow derived stem cells (BMSC) from unloaded bone fail to respond to IGF-1 in vitro. IGF-1R is required for the transduction of a mechanical stimulus to downstream effectors, transduction which is lost when the IGF-1R is deleted. Although the molecular mechanisms are not yet fully elucidated, the IGF signaling pathway and its interactions with potentially interlinked signaling cascades involving integrins, the estrogen receptor, and wnt/β-catenin play an important role in regulating adaptive response of cancer bone cells to mechanical stimuli. In this review, we discuss recent advances investigating how IGF-1 and other interlinked molecules and signaling pathways regulate skeletal mechano-transduction involving different bone cells, providing an overview of the IGF-1 signaling mediated cell-specific response to mechanical stimuli. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:576-583, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

High Efficiency Room Air Conditioner

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bansal, Pradeep

This project was undertaken as a CRADA project between UT-Battelle and Geberal Electric Company and was funded by Department of Energy to design and develop of a high efficiency room air conditioner. A number of novel elements were investigated to improve the energy efficiency of a state-of-the-art WAC with base capacity of 10,000 BTU/h. One of the major modifications was made by downgrading its capacity from 10,000 BTU/hr to 8,000 BTU/hr by replacing the original compressor with a lower capacity (8,000 BTU/hr) but high efficiency compressor having an EER of 9.7 as compared with 9.3 of the original compressor. However,more » all heat exchangers from the original unit were retained to provide higher EER. The other subsequent major modifications included- (i) the AC fan motor was replaced by a brushless high efficiency ECM motor along with its fan housing, (ii) the capillary tube was replaced with a needle valve to better control the refrigerant flow and refrigerant set points, and (iii) the unit was tested with a drop-in environmentally friendly binary mixture of R32 (90% molar concentration)/R125 (10% molar concentration). The WAC was tested in the environmental chambers at ORNL as per the design rating conditions of AHAM/ASHRAE (Outdoor- 95F and 40%RH, Indoor- 80F, 51.5%RH). All these modifications resulted in enhancing the EER of the WAC by up to 25%.« less

Photon-trapping microstructures enable high-speed high-efficiency silicon photodiodes

NASA Astrophysics Data System (ADS)

Gao, Yang; Cansizoglu, Hilal; Polat, Kazim G.; Ghandiparsi, Soroush; Kaya, Ahmet; Mamtaz, Hasina H.; Mayet, Ahmed S.; Wang, Yinan; Zhang, Xinzhi; Yamada, Toshishige; Devine, Ekaterina Ponizovskaya; Elrefaie, Aly F.; Wang, Shih-Yuan; Islam, M. Saif

2017-04-01

High-speed, high-efficiency photodetectors play an important role in optical communication links that are increasingly being used in data centres to handle higher volumes of data traffic and higher bandwidths, as big data and cloud computing continue to grow exponentially. Monolithic integration of optical components with signal-processing electronics on a single silicon chip is of paramount importance in the drive to reduce cost and improve performance. We report the first demonstration of micro- and nanoscale holes enabling light trapping in a silicon photodiode, which exhibits an ultrafast impulse response (full-width at half-maximum) of 30 ps and a high efficiency of more than 50%, for use in data-centre optical communications. The photodiode uses micro- and nanostructured holes to enhance, by an order of magnitude, the absorption efficiency of a thin intrinsic layer of less than 2 µm thickness and is designed for a data rate of 20 gigabits per second or higher at a wavelength of 850 nm. Further optimization can improve the efficiency to more than 70%.

Incremental Transductive Learning Approaches to Schistosomiasis Vector Classification

NASA Astrophysics Data System (ADS)

Fusco, Terence; Bi, Yaxin; Wang, Haiying; Browne, Fiona

2016-08-01

The key issues pertaining to collection of epidemic disease data for our analysis purposes are that it is a labour intensive, time consuming and expensive process resulting in availability of sparse sample data which we use to develop prediction models. To address this sparse data issue, we present the novel Incremental Transductive methods to circumvent the data collection process by applying previously acquired data to provide consistent, confidence-based labelling alternatives to field survey research. We investigated various reasoning approaches for semi-supervised machine learning including Bayesian models for labelling data. The results show that using the proposed methods, we can label instances of data with a class of vector density at a high level of confidence. By applying the Liberal and Strict Training Approaches, we provide a labelling and classification alternative to standalone algorithms. The methods in this paper are components in the process of reducing the proliferation of the Schistosomiasis disease and its effects.

HIGH EFFICIENCY SYNGAS GENERATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robert J. Copeland; Yevgenia Gershanovich; Brian Windecker

2005-02-01

This project investigated an efficient and low cost method of auto-thermally reforming natural gas to hydrogen and carbon monoxide. Reforming is the highest cost step in producing products such as methanol and Fisher Tropsch liquids (i.e., gas to liquids); and reducing the cost of reforming is the key to reducing the cost of these products. Steam reforming is expensive because of the high cost of the high nickel alloy reforming tubes (i.e., indirectly fired reforming tubes). Conventional auto-thermal or Partial Oxidation (POX) reforming minimizes the size and cost of the reformers and provides a near optimum mixture of CO andmore » hydrogen. However POX requires pure oxygen, which consumes power and significantly increases the cost to reforming. Our high efficiency process extracts oxygen from low-pressure air with novel oxygen sorbent and transfers the oxygen to a nickel-catalyzed reformer. The syngas is generated at process pressure (typically 20 to 40 bar) without nitrogen dilution and has a 1CO to 2H{sub 2} ratio that is near optimum for the subsequent production of Fisher-Tropsch liquid to liquids and other chemicals (i.e., Gas to Liquids, GTL). Our high process efficiency comes from the way we transfer the oxygen into the reformer. All of the components of the process, except for the oxygen sorbent, are commonly used in commercial practice. A process based on a longlived, regenerable, oxygen transfer sorbent could substantially reduce the cost of natural gas reforming to syngas. Lower cost syngas (CO + 2H{sub 2}) that is the feedstock for GTL would reduce the cost of GTL and for other commercial applications (e.g., methanol, other organic chemicals). The vast gas resources of Alaska's North Slope (ANS) offer more than 22 Tcf of gas and GTL production in this application alone, and could account for as much as 300,000 to 700,000 bpd for 20 to 30+ years. We developed a new sorbent, which is an essential part of the High Efficiency Oxygen Process (HOP). We

MDA5 and LGP2: Accomplices and Antagonists of Antiviral Signal Transduction

PubMed Central

Rodriguez, Kenny R.; Bruns, Annie M.

2014-01-01

Mammalian cells have the ability to recognize virus infection and mount a powerful antiviral transcriptional response that provides an initial barrier to replication and impacts both innate and adaptive immune responses. Retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) proteins mediate intracellular virus recognition and are activated by viral RNA ligands to induce antiviral signal transduction. While the mechanisms of RIG-I regulation are already well understood, less is known about the more enigmatic melanoma differentiation-associated 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2). Emerging evidence suggests that these two RLRs are intimately associated as both accomplices and antagonists of antiviral signal transduction. PMID:24850739

Analysis of signal transduction in cell-free extracts and rafts of Xenopus eggs.

PubMed

Tokmakov, Alexander A; Iwasaki, Tetsushi; Sato, Ken-Ichi; Fukami, Yasuo

2010-05-01

Intracellular signaling during egg activation/fertilization has been extensively studied using intact eggs, which can be manipulated by microinjection of different mRNAs, proteins, or chemical drugs. Furthermore, egg extracts, which retain high CSF activity (CSF-arrested extracts), were developed for studying fertilization/activation signal transduction, which have significant advantages as a model system. The addition of calcium to CSF-arrested extracts initiates a plethora of signaling events that take place during egg activation. Hence, the signaling downstream of calcium mobilization has been successfully studied in the egg extracts. Moreover, despite disruption of membrane-associated signaling compartments and ordered compartmentalization during extract preparation, CSF-arrested extracts can be successfully used to study early signaling events, which occur upstream of calcium release during egg activation/fertilization. In combination with the CSF-arrested extracts, activated egg rafts can reproduce some events of egg activation, including PLCgamma activation, IP3 production, transient calcium release, MAPK inactivation, and meiotic exit. This becomes possible due to complementation of the sperm-induced egg activation signaling machinery present in the rafts with the components of signal transduction system localized in the extracts. Herein, we describe protocols for studying molecular mechanisms of egg fertilization/activation using cell-free extracts and membrane rafts prepared from metaphase-arrested Xenopus eggs.

High-efficiency chiral meta-lens.

PubMed

Groever, Benedikt; Rubin, Noah A; Mueller, J P Balthasar; Devlin, Robert C; Capasso, Federico

2018-05-08

We present here a compact metasurface lens element that enables simultaneous and spatially separated imaging of light of opposite circular polarization states. The design overcomes a limitation of previous chiral lenses reliant on the traditional geometric phase approach by allowing for independent focusing of both circular polarizations without a 50% efficiency trade-off. We demonstrate circular polarization-dependent imaging at visible wavelengths with polarization contrast greater than 20dB and efficiencies as high as 70%.

Wnt signal transduction pathways: modules, development and evolution.

PubMed

Nayak, Losiana; Bhattacharyya, Nitai P; De, Rajat K

2016-08-01

Wnt signal transduction pathway (Wnt STP) is a crucial intracellular pathway mainly due to its participation in important biological processes, functions, and diseases, i.e., embryonic development, stem-cell management, and human cancers among others. This is why Wnt STP is one of the highest researched signal transduction pathways. Study and analysis of its origin, expansion and gradual development to the present state as found in humans is one aspect of Wnt research. The pattern of development and evolution of the Wnt STP among various species is not clear till date. A phylogenetic tree created from Wnt STPs of multiple species may address this issue. In this respect, we construct a phylogenetic tree from modules of Wnt STPs of diverse species. We term it as the 'Module Tree'. A module is nothing but a self-sufficient minimally-dependent subset of the original Wnt STP. Authenticity of the module tree is tested by comparing it with the two reference trees. The module tree performs better than an alternative phylogenetic tree constructed from pathway topology of Wnt STPs. Moreover, an evolutionary emergence pattern of the Wnt gene family is created and the module tree is tallied with it to showcase the significant resemblances.

Transfer functions for protein signal transduction: application to a model of striatal neural plasticity.

PubMed

Scheler, Gabriele

2013-01-01

We present a novel formulation for biochemical reaction networks in the context of protein signal transduction. The model consists of input-output transfer functions, which are derived from differential equations, using stable equilibria. We select a set of "source" species, which are interpreted as input signals. Signals are transmitted to all other species in the system (the "target" species) with a specific delay and with a specific transmission strength. The delay is computed as the maximal reaction time until a stable equilibrium for the target species is reached, in the context of all other reactions in the system. The transmission strength is the concentration change of the target species. The computed input-output transfer functions can be stored in a matrix, fitted with parameters, and even recalled to build dynamical models on the basis of state changes. By separating the temporal and the magnitudinal domain we can greatly simplify the computational model, circumventing typical problems of complex dynamical systems. The transfer function transformation of biochemical reaction systems can be applied to mass-action kinetic models of signal transduction. The paper shows that this approach yields significant novel insights while remaining a fully testable and executable dynamical model for signal transduction. In particular we can deconstruct the complex system into local transfer functions between individual species. As an example, we examine modularity and signal integration using a published model of striatal neural plasticity. The modularizations that emerge correspond to a known biological distinction between calcium-dependent and cAMP-dependent pathways. Remarkably, we found that overall interconnectedness depends on the magnitude of inputs, with higher connectivity at low input concentrations and significant modularization at moderate to high input concentrations. This general result, which directly follows from the properties of individual transfer

MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the downregulation of WAVE2.

PubMed

Huang, C-L; Ueno, M; Liu, D; Masuya, D; Nakano, J; Yokomise, H; Nakagawa, T; Miyake, M

2006-10-19

Motility-related protein-1 (MRP-1/CD9) is involved in cell motility. We studied the change in the actin cytoskeleton, and the expression of actin-related protein (Arp) 2 and Arp3 and the Wiskott-Aldrich syndrome protein (WASP) family according to MRP-1/CD9 gene transduction into HT1080 cells. The frequency of cells with lamellipodia was significantly lower in MRP-1/CD9-transfected HT1080 cells than in control HT1080 cells (P<0.0001). MRP-1/CD9 gene transduction affected the subcellular localization of Arp2 and Arp3 proteins. Furthermore, MRP-1/CD9 gene transduction induced a downregulation of WAVE2 expression (P<0.0001). However, no difference was observed in the expression of Arp2, Arp3 or other WASPs. A neutralizing anti-MRP-1/CD9 monoclonal antibody inhibited downregulation of WAVE2 in MRP-1/CD9-transfected HT1080 cells (P<0.0001), and reversed the morphological effects of MRP-1/CD9 gene transduction. Furthermore, downregulation of WAVE2 by transfection of WAVE2-specific small interfering RNA (siRNA) mimicked the morphological effects of MRP-1/CD9 gene transduction and suppressed cell motility. However, transfection of each siRNA for Wnt1, Wnt2b1 or Wnt5a did not affect WAVE2 expression. Transfection of WAVE2-specific siRNA also did not affect expressions of these Wnts. These results indicate that MRP-1/CD9 regulates the actin cytoskeleton by downregulating of the WAVE2, through the Wnt-independent signal pathway.

Highly efficient monolithic dye-sensitized solar cells.

PubMed

Kwon, Jeong; Park, Nam-Gyu; Lee, Jun Young; Ko, Min Jae; Park, Jong Hyeok

2013-03-01

Monolithic dye-sensitized solar cells (M-DSSCs) provide an effective way to reduce the fabrication cost of general DSSCs since they do not require transparent conducting oxide substrates for the counter electrode. However, conventional monolithic devices have low efficiency because of the impediments resulting from counter electrode materials and spacer layers. Here, we demonstrate highly efficient M-DSSCs featuring a highly conductive polymer combined with macroporous polymer spacer layers. With M-DSSCs based on a PEDOT/polymer spacer layer, a power conversion efficiency of 7.73% was achieved, which is, to the best of our knowledge, the highest efficiency for M-DSSCs to date. Further, PEDOT/polymer spacer layers were applied to flexible DSSCs and their cell performance was investigated.

Technology Development for High Efficiency Optical Communications

NASA Technical Reports Server (NTRS)

Farr, William H.

2012-01-01

Deep space optical communications is a significantly more challenging operational domain than near Earth space optical communications, primarily due to effects resulting from the vastly increased range between transmitter and receiver. The NASA Game Changing Development Program Deep Space Optical Communications Project is developing four key technologies for the implementation of a high efficiency telecommunications system that will enable greater than 10X the data rate of a state-of-the-art deep space RF system (Ka-band) for similar transceiver mass and power burden on the spacecraft. These technologies are a low mass spacecraft disturbance isolation assembly, a flight qualified photon counting detector array, a high efficiency flight laser amplifier and a high efficiency photon counting detector array for the ground-based receiver.

Transcription factor-based modulation of neural stem cell differentiation using direct protein transduction

PubMed Central

Stock, Kristin; Nolden, Lars; Edenhofer, Frank; Quandel, Tamara

2010-01-01

In contrast to conventional gene transfer strategies, the direct introduction of recombinant proteins into cells bypasses the risk of insertional mutagenesis and offers an alternative to genetic intervention. Here, we explore whether protein transduction of the gliogenic transcription factor Nkx2.2 can be used to promote oligodendroglial differentiation of mouse embryonic stem cell (ESC)-derived neural stem cells (NSC). To that end, a recombinant cell-permeant form of Nkx2.2 protein was generated. Exposure of ESC-derived NSC to the recombinant protein and initiation of differentiation resulted in a two-fold increase in the number of oligodendrocytes. Furthermore, Nkx2.2-transduced cells exhibited a more mature oligodendroglial phenotype. Comparative viral gene transfer studies showed that the biological effect of Nkx2.2 protein transduction is comparable to that obtained by lentiviral transduction. The results of this proof-of-concept study depict direct intracellular delivery of transcription factors as alternative modality to control lineage differentiation in NSC cultures without genetic modification. Electronic supplementary material The online version of this article (doi:10.1007/s00018-010-0347-1) contains supplementary material, which is available to authorized users. PMID:20352468

SigFlux: a novel network feature to evaluate the importance of proteins in signal transduction networks.

PubMed

Liu, Wei; Li, Dong; Zhang, Jiyang; Zhu, Yunping; He, Fuchu

2006-11-27

Measuring each protein's importance in signaling networks helps to identify the crucial proteins in a cellular process, find the fragile portion of the biology system and further assist for disease therapy. However, there are relatively few methods to evaluate the importance of proteins in signaling networks. We developed a novel network feature to evaluate the importance of proteins in signal transduction networks, that we call SigFlux, based on the concept of minimal path sets (MPSs). An MPS is a minimal set of nodes that can perform the signal propagation from ligands to target genes or feedback loops. We define SigFlux as the number of MPSs in which each protein is involved. We applied this network feature to the large signal transduction network in the hippocampal CA1 neuron of mice. Significant correlations were simultaneously observed between SigFlux and both the essentiality and evolutionary rate of genes. Compared with another commonly used network feature, connectivity, SigFlux has similar or better ability as connectivity to reflect a protein's essentiality. Further classification according to protein function demonstrates that high SigFlux, low connectivity proteins are abundant in receptors and transcriptional factors, indicating that SigFlux candescribe the importance of proteins within the context of the entire network. SigFlux is a useful network feature in signal transduction networks that allows the prediction of the essentiality and conservation of proteins. With this novel network feature, proteins that participate in more pathways or feedback loops within a signaling network are proved far more likely to be essential and conserved during evolution than their counterparts.

Genetic Analysis of Gravity Signal Transduction in Arabidopsis thaliana Seedlings

NASA Astrophysics Data System (ADS)

Boonsirichai, K.; Harrison, B.; Stanga, J.; Young, L.-S.; Neal, C.; Sabat, G.; Murthy, N.; Harms, A.; Sedbrook, J.; Masson, P.

The primary roots of Arabidopsis thaliana seedlings respond to gravity stimulation by developing a tip curvature that results from differential cellular elongation on opposite flanks of the elongation zone. This curvature appears modulated by a lateral gradient of auxin that originates in the gravity-perceiving cells (statocytes) of the root cap through an apparent lateral repositioning of a component the auxin efflux carrier complex within these cells (Friml et al, 2002, Nature 415: 806-809). Unfortunately, little is known about the molecular mechanisms that govern early phases of gravity perception and signal transduction within the root-cap statocytes. We have used a molecular genetic approach to uncover some of these mechanisms. Mutations in the Arabidopsis ARG1 and ARL2 genes, which encode J-domain proteins, resulted in specific alterations in root and hypocotyl gravitropism, without pleiotropic phenotypes. Interestingly, ARG1 and ARL2 appear to function in the same genetic pathway. A combination of molecular genetic, biochemical and cell-biological approaches were used to demonstrate that ARG1 functions in early phases of gravity signal transduction within the root and hypocotyl statocytes, and is needed for efficient lateral auxin transport within the cap. The ARG1 protein is associated with components of the secretory and/or endosomal pathways, suggesting its role in the recycling of components of the auxin efflux carrier complex between plasma membrane and endosome (Boonsirichai et al, 2003, Plant Cell 15:2612-2625). Genetic modifiers of arg1-2 were isolated and shown to enhance the gravitropic defect of arg1-2, while resulting in little or no gravitropic defects in a wild type ARG1 background. A slight tendency for arg1-2;mar1-1 and arg1-2;mar2-1 double-mutant organs to display an opposite gravitropic response compared to wild type suggests that all three genes contribute to the interpretation of the gravity-vector information by seedling organs. The

The mechanisms of Ag85A DNA vaccine activates RNA sensors through new signal transduction.

PubMed

Zhai, Jingbo; Wang, Qiubo; Gao, Yunfeng; Zhang, Ran; Li, Shengjun; Wei, Bing; You, Yong; Sun, Xun; Lu, Changlong

2018-06-01

Low immunogenicity is one of the major problems limiting the clinical use for DNA vaccines, which makes it impossible to obtain a strong protective immune response after vaccination. In order to explore whether Ag85A DNA vaccine could mount more efficiently protective immune response through new RNA sensor and its signal transduction pathway of antigen presentation we designed and synthesized Ag85A gene fragment containing multiple points mutations and transfected the gene fragment into the dendritic cell line (DC2.4) by CRISPR/Cas9. Subsequently, we focused on the changes of RNA sensors RIG-I, Mda-5, and the downstream adaptors MAVS, IRF3, IRF7 and IFN-β. The results indicated the significant increases in the mRNA and protein expression of RNA sensors RIG-I, Mda-5 and related adaptors MAVS, IRF3, IRF7, and IFN-β in the mutant DC 2.4 cells. The flow cytometry results demonstrated that the expression of MHC II on the surface of DC 2.4 significantly increased when compared with that in control. Therefore, it is suggested that Ag85A mutant DNA could release immunogenic message through RNA sensors and related adaptors via non protein pathway. There is at least one RNA signal transduction pathway of Ag85A DNA in DC2.4 cell. The work provides a new mode of action for nucleic acid vaccine to improve immunogenicity and meaningful data for the better understanding of the mechanisms of DNA vaccine. Copyright © 2017. Published by Elsevier B.V.

Code TESLA for Modeling and Design of High-Power High-Efficiency Klystrons

DTIC Science & Technology

2011-03-01

CODE TESLA FOR MODELING AND DESIGN OF HIGH - POWER HIGH -EFFICIENCY KLYSTRONS * I.A. Chernyavskiy, SAIC, McLean, VA 22102, U.S.A. S.J. Cooke, B...and multiple-beam klystrons as high - power RF sources. These sources are widely used or proposed to be used in accelerators in the future. Comparison...of TESLA modelling results with experimental data for a few multiple-beam klystrons are shown. INTRODUCTION High - power and high -efficiency

High efficiency novel window air conditioner

DOE PAGES

Bansal, Pradeep

2015-07-24

This paper presents the technical development of a high efficiency window air conditioner. In order to achieve higher energy efficiency ratio (EER), the original capacity of the R410A unit was downgraded by replacing the original compressor with a lower capacity but higher EER compressor, while all heat exchangers and the chassis from the original unit were retained. The other subsequent major modifications included – the AC fan motor being replaced with a brushless high efficiency electronically commuted motor (ECM) motor, the capillary tube being replaced with a needle valve to better control the refrigerant flow and refrigerant set points, andmore » R410A being replaced with drop-in environmentally friendly binary mixture of R32 (85% molar concentration)/R125 (15% molar concentration). All these modifications resulted in significant EER enhancement of the modified unit.« less

High efficiency novel window air conditioner

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bansal, Pradeep

This paper presents the technical development of a high efficiency window air conditioner. In order to achieve higher energy efficiency ratio (EER), the original capacity of the R410A unit was downgraded by replacing the original compressor with a lower capacity but higher EER compressor, while all heat exchangers and the chassis from the original unit were retained. The other subsequent major modifications included – the AC fan motor being replaced with a brushless high efficiency electronically commuted motor (ECM) motor, the capillary tube being replaced with a needle valve to better control the refrigerant flow and refrigerant set points, andmore » R410A being replaced with drop-in environmentally friendly binary mixture of R32 (85% molar concentration)/R125 (15% molar concentration). All these modifications resulted in significant EER enhancement of the modified unit.« less

Development and characterization of high-efficiency, high-specific impulse xenon Hall thrusters

NASA Astrophysics Data System (ADS)

Hofer, Richard Robert

This dissertation presents research aimed at extending the efficient operation of 1600 s specific impulse Hall thruster technology to the 2000--3000 s range. While recent studies of commercially developed Hall thrusters demonstrated greater than 4000 s specific impulse, maximum efficiency occurred at less than 3000 s. It was hypothesized that the efficiency maximum resulted as a consequence of modern magnetic field designs, optimized for 1600 s, which were unsuitable at high-specific impulse. Motivated by the industry efforts and mission studies, the aim of this research was to develop and characterize xenon Hall thrusters capable of both high-specific impulse and high-efficiency operation. The research divided into development and characterization phases. During the development phase, the laboratory-model NASA-173M Hall thrusters were designed with plasma lens magnetic field topographies and their performance and plasma characteristics were evaluated. Experiments with the NASA-173M version 1 (v1) validated the plasma lens design by showing how changing the magnetic field topography at high-specific impulse improved efficiency. Experiments with the NASA-173M version 2 (v2) showed there was a minimum current density and optimum magnetic field topography at which efficiency monotonically increased with voltage. Between 300--1000 V, total specific impulse and total efficiency of the NASA-173Mv2 operating at 10 mg/s ranged from 1600--3400 s and 51--61%, respectively. Comparison of the thrusters showed that efficiency can be optimized for specific impulse by varying the plasma lens design. During the characterization phase, additional plasma properties of the NASA-173Mv2 were measured and a performance model was derived accounting for a multiply-charged, partially-ionized plasma. Results from the model based on experimental data showed how efficient operation at high-specific impulse was enabled through regulation of the electron current with the magnetic field. The

A high-efficiency high-power-generation system for automobiles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naidu, M.; Boules, N.; Henry, R.

This paper presents a new scheme for the efficient generation of high electric power demanded for future automobiles. The new system consists of a permanent-magnet (PM) alternator having high-energy MAGNEQUENCH (MQ) magnets and split winding and a novel electronic voltage-regulation scheme. A proof-of-concept system, capable of providing 100/250 A (idle/cruising) at 14 V, has been built and tested in the laboratory with encouraging results. This high output is provided at 15--20 percentage points higher efficiencies than conventional automotive alternators, which translates into considerable fuel economy savings. The system is 8 dB quieter and has a rotor inertia of only 2/3more » that of an equivalent production alternator, thus allowing for a belt drive without excessive slippage.« less

A high-efficiency, high power generation system for automobiles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naidu, M.; Boules, N.; Henry, R.

The paper presents a new scheme for the efficient generation of high electric power, demands for future automobiles. The new system, consists of a permanent magnet (PM) alternator having high energy MAGNEQUENCH (MQ) magnets and split winding; and a novel electronic voltage regulation scheme. A proof of concept system, capable of providing 100/250 A (idle/cruising) at 14 V, has been built and tested in the laboratory with encouraging results. This high output is provided at 15--20 percentage points higher efficiencies than conventional automotive alternators, which translates into considerable fuel economy savings. The system is 8 dB quieter and has amore » rotor inertia of only 2/3 that of an equivalent production alternator, thus allowing for a belt drive without excessive slippage.« less

High-efficiency white OLEDs based on small molecules

NASA Astrophysics Data System (ADS)

Hatwar, Tukaram K.; Spindler, Jeffrey P.; Ricks, M. L.; Young, Ralph H.; Hamada, Yuuhiko; Saito, N.; Mameno, Kazunobu; Nishikawa, Ryuji; Takahashi, Hisakazu; Rajeswaran, G.

2004-02-01

Eastman Kodak Company and SANYO Electric Co., Ltd. recently demonstrated a 15" full-color, organic light-emitting diode display (OLED) using a high-efficiency white emitter combined with a color-filter array. Although useful for display applications, white emission from organic structures is also under consideration for other applications, such as solid-state lighting, where high efficiency and good color rendition are important. By incorporating adjacent blue and orange emitting layers in a multi-layer structure, highly efficient, stable white emission has been attained. With suitable host and dopant combinations, a luminance yield of 20 cd/A and efficiency of 8 lm/W have been achieved at a drive voltage of less than 8 volts and luminance level of 1000 cd/m2. The estimated external efficiency of this device is 6.3% and a high level of operational stability is observed. To our knowledge, this is the highest performance reported so far for white organic electroluminescent devices. We will review white OLED technology and discuss the fabrication and operating characteristics of these devices.

Rice PLASTOCHRON genes regulate leaf maturation downstream of the gibberellin signal transduction pathway.

PubMed

Mimura, Manaki; Nagato, Yasuo; Itoh, Jun-Ichi

2012-05-01

Rice PLASTOCHRON 1 (PLA1) and PLA2 genes regulate leaf maturation and plastochron, and their loss-of-function mutants exhibit small organs and rapid leaf emergence. They encode a cytochrome P450 protein CYP78A11 and an RNA-binding protein, respectively. Their homologs in Arabidopsis and maize are also associated with plant development/organ size. Despite the importance of PLA genes in plant development, their molecular functions remain unknown. Here, we investigated how PLA1 and PLA2 genes are related to phytohormones. We found that gibberellin (GA) is the major phytohormone that promotes PLA1 and PLA2 expression. GA induced PLA1 and PLA2 expression, and conversely the GA-inhibitor uniconazole suppressed PLA1 and PLA2 expression. In pla1-4 and pla2-1 seedlings, expression levels of GA biosynthesis genes and the signal transduction gene were similar to those in wild-type seedlings. GA treatment slightly down-regulated the GA biosynthesis gene GA20ox2 and up-regulated the GA-catabolizing gene GA2ox4, whereas the GA biosynthesis inhibitor uniconazole up-regulated GA20ox2 and down-regulated GA2ox4 both in wild-type and pla mutants, suggesting that the GA feedback mechanism is not impaired in pla1 and pla2. To reveal how GA signal transduction affects the expression of PLA1 and PLA2, PLA expression in GA-signaling mutants was examined. In GA-insensitive mutant, gid1 and less-sensitive mutant, Slr1-d1, PLA1 and PLA2 expression was down-regulated. On the other hand, the expression levels of PLA1 and PLA2 were highly enhanced in a GA-constitutive-active mutant, slr1-1, causing ectopic overexpression. These results indicate that both PLA1 and PLA2 act downstream of the GA signal transduction pathway to regulate leaf development.

Receptor clustering affects signal transduction at the membrane level in the reaction-limited regime

NASA Astrophysics Data System (ADS)

Caré, Bertrand R.; Soula, Hédi A.

2013-01-01

Many types of membrane receptors are found to be organized as clusters on the cell surface. We investigate the potential effect of such receptor clustering on the intracellular signal transduction stage. We consider a canonical pathway with a membrane receptor (R) activating a membrane-bound intracellular relay protein (G). We use Monte Carlo simulations to recreate biochemical reactions using different receptor spatial distributions and explore the dynamics of the signal transduction. Results show that activation of G by R is severely impaired by R clustering, leading to an apparent blunted biological effect compared to control. Paradoxically, this clustering decreases the half maximal effective dose (ED50) of the transduction stage, increasing the apparent affinity. We study an example of inter-receptor interaction in order to account for possible compensatory effects of clustering and observe the parameter range in which such interactions slightly counterbalance the loss of activation of G. The membrane receptors’ spatial distribution affects the internal stages of signal amplification, suggesting a functional role for membrane domains and receptor clustering independently of proximity-induced receptor-receptor interactions.

Phosphoglycerolipids are master players in plant hormone signal transduction.

PubMed

Janda, Martin; Planchais, Severine; Djafi, Nabila; Martinec, Jan; Burketova, Lenka; Valentova, Olga; Zachowski, Alain; Ruelland, Eric

2013-06-01

Phosphoglycerolipids are essential structural constituents of membranes and some also have important cell signalling roles. In this review, we focus on phosphoglycerolipids that are mediators in hormone signal transduction in plants. We first describe the structures of the main signalling phosphoglycerolipids and the metabolic pathways that generate them, namely the phospholipase and lipid kinase pathways. In silico analysis of Arabidopsis transcriptome data provides evidence that the genes encoding the enzymes of these pathways are transcriptionally regulated in responses to hormones, suggesting some link with hormone signal transduction. The involvement of phosphoglycerolipid signalling in the early responses to abscisic acid, salicylic acid and auxins is then detailed. One of the most important signalling lipids in plants is phosphatidic acid. It can activate or inactivate protein kinases and/or protein phosphatases involved in hormone signalling. It can also activate NADPH oxidase leading to the production of reactive oxygen species. We will interrogate the mechanisms that allow the activation/deactivation of the lipid pathways, in particular the roles of G proteins and calcium. Mediating lipids thus appear as master players of cell signalling, modulating, if not controlling, major transducing steps of hormone signals.

High Efficiency Low Global Warming Potential Compressor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cogswell, Frederick; Verma, Parmesh

During this project UTRC designed a novel compressor for use with new low Global-Warming-Potential (GWP) refrigerants. Through two design and testing iterations, UTRC advanced the compressor technology from TRL3 to TRL5. The target application was a 5 Tons of Refrigeration (TR) capacity Roof-Top Unit (RTU), although this technology may be applied to other low-capacity systems such as residential. The prototype unit met all design goals at the ARI-A rating condition and requires high efficiency motor to meet high performance targets at the ARI-B condition. This technology may be used in high efficiency units and with seasonal energy efficiency rating (SEER)more » exceeding 20. A preliminary cost analysis estimated that there would be less than $25/kbtuh cost impact to the customer.« less

Lentiviral transduction of rat Sertoli cells as a means to modify gene expression

PubMed Central

Nicholls, Peter K.; Stanton, Peter G.; Rainczuk, Katarzyna E.; Qian, Hongwei; Gregorevic, Paul; Harrison, Craig A.

2012-01-01

Primary cell culture is an established and widely used technique to study Sertoli cell function in vitro. However, the relative difficulty of stably overexpressing or knocking down genes in Sertoli cell culture has limited progress in the field. In this technical report, we present a method to transduce 20 dpp rat Sertoli cell cultures with VSV-G pseudotyped lentiviral based vectors at a high rate (~80%), with stable reporter gene expression. Although high transgene expression is desirable, it was noted that at transduction rates > 60% inter-Sertoli cell tight junction integrity and, hence, Sertoli cell function, were transiently compromised. We envisage that this optimized procedure has the potential to stimulate Sertoli cell research, and motivate the use of Sertoli cells in various cell therapy applications. PMID:23248769

FASEB summer research conference on signal transduction in plants. Final report, June 16, 1996--June 21, 1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lomax, T.L.; Quatrano, R.S.

1996-12-31

This is the program from the second FASEB conference on Signal Transduction in Plants. Topic areas included the following: environmental signaling; perception and transduction of light signals; signaling in plant microbe interactions; signaling in plant pathogen interactions; cell, cell communication; cytoskeleton, plasma membrane, and cellwall continuum; signaling molecules in plant growth and development I and II. A list of participants is included.

The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part II: signal transduction.

PubMed

Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

2015-02-01

The unique mechanoelectrochemical environment of cartilage has motivated researchers to investigate the effect of multiple biophysical cues, including mechanical, magnetic, and electrical stimulation, on chondrocyte biology. It is well established that biophysical stimuli promote chondrocyte proliferation, differentiation, and maturation within "biological windows" of defined dose parameters, including mode, frequency, magnitude, and duration of stimuli (see companion review Part I: Cellular Response). However, the underlying molecular mechanisms and signal transduction pathways activated in response to multiple biophysical stimuli remain to be elucidated. Understanding the mechanisms of biophysical signal transduction will deepen knowledge of tissue organogenesis, remodeling, and regeneration and aiding in the treatment of pathologies such as osteoarthritis. Further, this knowledge will provide the tissue engineer with a potent toolset to manipulate and control cell fate and subsequently develop functional replacement cartilage. The aim of this article is to review chondrocyte signal transduction pathways in response to mechanical, magnetic, and electrical cues. Signal transduction does not occur along a single pathway; rather a number of parallel pathways appear to be activated, with calcium signaling apparently common to all three types of stimuli, though there are different modes of activation. Current tissue engineering strategies, such as the development of "smart" functionalized biomaterials that enable the delivery of growth factors or integration of conjugated nanoparticles, may further benefit from targeting known signal transduction pathways in combination with external biophysical cues.

Prediction of Enzyme Mutant Activity Using Computational Mutagenesis and Incremental Transduction

PubMed Central

Basit, Nada; Wechsler, Harry

2011-01-01

Wet laboratory mutagenesis to determine enzyme activity changes is expensive and time consuming. This paper expands on standard one-shot learning by proposing an incremental transductive method (T2bRF) for the prediction of enzyme mutant activity during mutagenesis using Delaunay tessellation and 4-body statistical potentials for representation. Incremental learning is in tune with both eScience and actual experimentation, as it accounts for cumulative annotation effects of enzyme mutant activity over time. The experimental results reported, using cross-validation, show that overall the incremental transductive method proposed, using random forest as base classifier, yields better results compared to one-shot learning methods. T2bRF is shown to yield 90% on T4 and LAC (and 86% on HIV-1). This is significantly better than state-of-the-art competing methods, whose performance yield is at 80% or less using the same datasets. PMID:22007208

Toward high-energy-density, high-efficiency, and moderate-temperature chip-scale thermophotovoltaics

PubMed Central

Chan, Walker R.; Bermel, Peter; Pilawa-Podgurski, Robert C. N.; Marton, Christopher H.; Jensen, Klavs F.; Senkevich, Jay J.; Joannopoulos, John D.; Soljačić, Marin; Celanovic, Ivan

2013-01-01

The challenging problem of ultra-high-energy-density, high-efficiency, and small-scale portable power generation is addressed here using a distinctive thermophotovoltaic energy conversion mechanism and chip-based system design, which we name the microthermophotovoltaic (μTPV) generator. The approach is predicted to be capable of up to 32% efficient heat-to-electricity conversion within a millimeter-scale form factor. Although considerable technological barriers need to be overcome to reach full performance, we have performed a robust experimental demonstration that validates the theoretical framework and the key system components. Even with a much-simplified μTPV system design with theoretical efficiency prediction of 2.7%, we experimentally demonstrate 2.5% efficiency. The μTPV experimental system that was built and tested comprises a silicon propane microcombustor, an integrated high-temperature photonic crystal selective thermal emitter, four 0.55-eV GaInAsSb thermophotovoltaic diodes, and an ultra-high-efficiency maximum power-point tracking power electronics converter. The system was demonstrated to operate up to 800 °C (silicon microcombustor temperature) with an input thermal power of 13.7 W, generating 344 mW of electric power over a 1-cm2 area. PMID:23440220

Adenoviral vector tethering to metal surfaces via hydrolysable cross-linkers for the modulation of vector release and transduction

PubMed Central

Fishbein, Ilia; Forbes, Scott P.; Chorny, Michael; Connolly, Jeanne M.; Adamo, Richard F.; Corrales, Ricardo; Alferiev, Ivan S.; Levy, Robert J.

2013-01-01

The use of arterial stents and other medical implants as a delivery platform for surface immobilized gene vectors allows for safe and efficient localized expression of therapeutic transgenes. In this study we investigate the use of hydrolysable cross-linkers with distinct kinetics of hydrolysis for delivery of gene vectors from polyallylamine bisphosphonate-modified metal surfaces. Three cross-linkers with the estimated t1/2 of ester bonds hydrolysis of 5, 12 and 50 days demonstrated a cumulative 20%, 39% and 45% vector release, respectively, after 30 days exposure to physiological buffer at 37°C. Transgene expression in endothelial and smooth muscles cells transduced with substrate immobilized adenovirus resulted in significantly different expression profiles for each individual cross-linker. Furthermore, immobilization of adenoviral vectors effectively extended their transduction effectiveness beyond the initial phase of release. Transgene expression driven by adenovirus-tethered stents in rat carotid arteries demonstrated that a faster rate of cross-linker hydrolysis resulted in higher expression levels at day 1, which declined by day 8 after stent implantation, while inversely, slower hydrolysis was associated with increased arterial expression at day 8 in comparison with day 1. In conclusion, adjustable release of transduction-competent adenoviral vectors from metallic surfaces can be achieved, both in vitro and in vivo, through surface immobilization of adenoviral vectors using hydrolysable cross-linkers with structure-specific release kinetics. PMID:23777912

Highly efficient and specific modulation of cardiac calcium homeostasis by adenovector-derived short hairpin RNA targeting phospholamban.

PubMed

Fechner, H; Suckau, L; Kurreck, J; Sipo, I; Wang, X; Pinkert, S; Loschen, S; Rekittke, J; Weger, S; Dekkers, D; Vetter, R; Erdmann, V A; Schultheiss, H-P; Paul, M; Lamers, J; Poller, W

2007-02-01

Impaired function of the phospholamban (PLB)-regulated sarcoplasmic reticulum Ca(2+) pump (SERCA2a) contributes to cardiac dysfunction in heart failure (HF). PLB downregulation may increase SERCA2a activity and improve cardiac function. Small interfering (si)RNAs mediate efficient gene silencing by RNA interference (RNAi). However, their use for in vivo gene therapy is limited by siRNA instability in plasma and tissues, and by low siRNA transfer rates into target cells. To address these problems, we developed an adenoviral vector (AdV) transcribing short hairpin (sh)RNAs against rat PLB and evaluated its potential to silence the PLB gene and to modulate SERCA2a-mediated Ca(2+) sequestration in primary neonatal rat cardiomyocytes (PNCMs). Over a period of 13 days, vector transduction resulted in stable > 99.9% ablation of PLB-mRNA at a multiplicity of infection of 100. PLB protein gradually decreased until day 7 (7+/-2% left), whereas SERCA, Na(+)/Ca(2+) exchanger (NCX1), calsequestrin and troponin I protein remained unchanged. PLB silencing was associated with a marked increase in ATP-dependent oxalate-supported Ca(2+) uptake at 0.34 microM of free Ca(2+), and rapid loss of responsiveness to protein kinase A-dependent stimulation of Ca(2+) uptake was maintained until day 7. In summary, these results indicate that AdV-derived PLB-shRNA mediates highly efficient, specific and stable PLB gene silencing and modulation of active Ca(2+) sequestration in PNCMs. The availability of the new vector now enables employment of RNAi for the treatment of HF in vivo.

A Genetic Approach to Identifying Signal Transduction Mechanisms Initiated by Receptors for TGF-B-Related Factors.

DTIC Science & Technology

1998-10-01

resistant to TGF-ß-induced growth arrest suggest that both types of receptors are required for signaling (Boyd and Massague, 1989; Laiho et ah, 1990...II in TGF-ß- resistant cell mutants implicates both receptor types in signal transduction. J. Biol. Chem. 265, 18518-18524. Lechleider, R. J., de...I-1 « -J AD GRANT NUMBER DAMD17-94-J-4339 TITLE: A Genetic Approach to Identifying Signal Transduction Mechanisms Initiated by Receptors

Expression of the synaptic exocytosis-regulating molecule complexin 2 in taste buds and its participation in peripheral taste transduction.

PubMed

Kurokawa, Azusa; Narukawa, Masataka; Ohmoto, Makoto; Yoshimoto, Joto; Abe, Keiko; Misaka, Takumi

2015-06-01

Taste information from type III taste cells to gustatory neurons is thought to be transmitted via synapses. However, the molecular mechanisms underlying taste transduction through this pathway have not been fully elucidated. In this study, to identify molecules that participate in synaptic taste transduction, we investigated whether complexins (Cplxs), which play roles in regulating membrane fusion in synaptic vesicle exocytosis, were expressed in taste bud cells. Among four Cplx isoforms, strong expression of Cplx2 mRNA was detected in type III taste cells. To investigate the function of CPLX2 in taste transduction, we observed taste responses in CPLX2-knockout mice. When assessed with electrophysiological and behavioral assays, taste responses to some sour stimuli in CPLX2-knockout mice were significantly lower than those in wild-type mice. These results suggested that CPLX2 participated in synaptic taste transduction from type III taste cells to gustatory neurons. A part of taste information is thought to be transmitted via synapses. However, the molecular mechanisms have not been fully elucidated. To identify molecules that participate in synaptic taste transduction, we investigated complexins (Cplxs) expression in taste bud cells. Strong expression of Cplx2 mRNA was detected in taste bud cells. Furthermore, taste responses to some sour stimuli in CPLX2- knockout mice were significantly lower than those in wild-type mice. These suggested that CPLX2 participated in synaptic taste transduction. © 2015 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of The International Society for Neurochemistry.

Diboron compound-based organic light-emitting diodes with high efficiency and reduced efficiency roll-off

NASA Astrophysics Data System (ADS)

Wu, Tien-Lin; Huang, Min-Jie; Lin, Chih-Chun; Huang, Pei-Yun; Chou, Tsu-Yu; Chen-Cheng, Ren-Wu; Lin, Hao-Wu; Liu, Rai-Shung; Cheng, Chien-Hong

2018-04-01

Organic light-emitting diodes (OLEDs) based on thermally activated delayed fluorescence (TADF) materials are promising for the realization of highly efficient light emitters. However, such devices have so far suffered from efficiency roll-off at high luminance. Here, we report the design and synthesis of two diboron-based molecules, CzDBA and tBuCzDBA, which show excellent TADF properties and yield efficient OLEDs with very low efficiency roll-off. These donor-acceptor-donor (D-A-D) type and rod-like compounds concurrently generate TADF with a photoluminescence quantum yield of 100% and an 84% horizontal dipole ratio in the thin film. A green OLED based on CzDBA exhibits a high external quantum efficiency of 37.8 ± 0.6%, a current efficiency of 139.6 ± 2.8 cd A-1 and a power efficiency of 121.6 ± 3.1 lm W-1 with an efficiency roll-off of only 0.3% at 1,000 cd m-2. The device has a peak emission wavelength of 528 nm and colour coordinates of the Commission International de ĺEclairage (CIE) of (0.31, 0.61), making it attractive for colour-display applications.

Superstructure high efficiency photovoltaics

NASA Technical Reports Server (NTRS)

Wagner, M.; So, L. C.; Leburton, J. P.

1987-01-01

A novel class of photovoltaic cascade structures is introduced which features multijunction upper subcells. These superstructure high efficiency photovoltaics (SHEP's) exhibit enhanced upper subcell spectral response because of the additional junctions which serve to reduce bulk recombination losses by decreasing the mean collection distance for photogenerated minority carriers. Two possible electrical configurations were studied and compared: a three-terminal scheme that allows both subcells to be operated at their individual maximum power points and a two-terminal configuration with an intercell ohmic contact for series interconnection. The three-terminal devices were found to be superior both in terms of beginning-of-life expectancy and radiation tolerance. Realistic simulations of three-terminal AlGaAs/GaAs SHEP's show that one sun AMO efficiencies in excess of 26 percent are possible.

High efficiency endocrine operation protocol: From design to implementation.

PubMed

Mascarella, Marco A; Lahrichi, Nadia; Cloutier, Fabienne; Kleiman, Simcha; Payne, Richard J; Rosenberg, Lawrence

2016-10-01

We developed a high efficiency endocrine operative protocol based on a mathematical programming approach, process reengineering, and value-stream mapping to increase the number of operations completed per day without increasing operating room time at a tertiary-care, academic center. Using this protocol, a case-control study of 72 patients undergoing endocrine operation during high efficiency days were age, sex, and procedure-matched to 72 patients undergoing operation during standard days. The demographic profile, operative times, and perioperative complications were noted. The average number of cases per 8-hour workday in the high efficiency and standard operating rooms were 7 and 5, respectively. Mean procedure times in both groups were similar. The turnaround time (mean ± standard deviation) in the high efficiency group was 8.5 (±2.7) minutes as compared with 15.4 (±4.9) minutes in the standard group (P < .001). Transient postoperative hypocalcemia was 6.9% (5/72) and 8.3% (6/72) for the high efficiency and standard groups, respectively (P = .99). In this study, patients undergoing high efficiency endocrine operation had similar procedure times and perioperative complications compared with the standard group. The proposed high efficiency protocol seems to better utilize operative time and decrease the backlog of patients waiting for endocrine operation in a country with a universal national health care program. Copyright © 2016 Elsevier Inc. All rights reserved.

Protein Tyrosine Phosphatases: From Housekeeping Enzymes to Master-Regulators of Signal Transduction

PubMed Central

Tonks, Nicholas K.

2013-01-01

There are many misconceptions surrounding the roles of protein phosphatases in the regulation of signal transduction, perhaps the most damaging of which is the erroneous view that these enzymes exert their effects merely as constitutively active housekeeping enzymes. On the contrary, the phosphatases are critical, specific regulators of signaling in their own right and serve an essential function, in a coordinated manner with the kinases, to determine the response to a physiological stimulus. This review is a personal perspective on the development of our understanding of the protein tyrosine phosphatase (PTP) family of enzymes. I have discussed various aspects of the structure, regulation and function of the PTP family, which I hope will illustrate the fundamental importance of these enzymes to the control of signal transduction. PMID:23176256

Processing technology for high efficiency silicon solar cells

NASA Technical Reports Server (NTRS)

Spitzer, M. B.; Keavney, C. J.

1985-01-01

Recent advances in silicon solar cell processing have led to attainment of conversion efficiency approaching 20%. The basic cell design is investigated and features of greatest importance to achievement of 20% efficiency are indicated. Experiments to separately optimize high efficiency design features in test structures are discussed. The integration of these features in a high efficiency cell is examined. Ion implantation has been used to achieve optimal concentrations of emitter dopant and junction depth. The optimization reflects the trade-off between high sheet conductivity, necessary for high fill factor, and heavy doping effects, which must be minimized for high open circuit voltage. A second important aspect of the design experiments is the development of a passivation process to minimize front surface recombination velocity. The manner in which a thin SiO2 layer may be used for this purpose is indicated without increasing reflection losses, if the antireflection coating is properly designed. Details are presented of processing intended to reduce recombination at the contact/Si interface. Data on cell performance (including CZ and ribbon) and analysis of loss mechanisms are also presented.

Signal transduction mechanisms in plants: an overview

NASA Technical Reports Server (NTRS)

Clark, G. B.; Thompson, G. Jr; Roux, S. J.

2001-01-01

This article provides an overview on recent advances in some of the basic signalling mechanisms that participate in a wide variety of stimulus-response pathways. The mechanisms include calcium-based signalling, G-protein-mediated-signalling and signalling involving inositol phospholipids, with discussion on the role of protein kinases and phosphatases interspersed. As a further defining feature, the article highlights recent exciting findings on three extracellular components that have not been given coverage in previous reviews of signal transduction in plants, extracellular calmodulin, extracellular ATP, and integrin-like receptors, all of which affect plant growth and development.

Enabling High Efficiency Nanoplasmonics with Novel Nanoantenna Architectures

PubMed Central

Cohen, Moshik; Shavit, Reuven; Zalevsky, Zeev

2015-01-01

Surface plasmon polaritons (SPPs) are propagating excitations that arise from coupling of light with collective electron oscillations. Characterized by high field intensity and nanometric dimensions, SPPs fashion rapid expansion of interest from fundamental and applicative perspectives. However, high metallic losses at optical frequencies still make nanoplasmonics impractical when high absolute efficiency is paramount, with major challenge is efficient plasmon generation in deep nanoscale. Here we introduce the Plantenna, the first reported nanodevice with the potential of addressing these limitations utilizing novel plasmonic architecture. The Plantenna has simple 2D structure, ultracompact dimensions and is fabricated on Silicon chip for future CMOS integration. We design the Plantenna to feed channel (20 nm × 20 nm) nanoplasmonic waveguides, achieving 52% coupling efficiency with Plantenna dimensions of λ3/17,000. We theoretically and experimentally show that the Plantenna enormously outperforms dipole couplers, achieving 28 dB higher efficiency with broad polarization diversity and huge local field enhancement. Our findings confirm the Plantenna as enabling device for high efficiency plasmonic technologies such as quantum nanoplasmonics, molecular strong coupling and plasmon nanolasers. PMID:26620270

Neutrophil cell surface receptors and their intracellular signal transduction pathways☆

PubMed Central

Futosi, Krisztina; Fodor, Szabina; Mócsai, Attila

2013-01-01

Neutrophils play a critical role in the host defense against bacterial and fungal infections, but their inappropriate activation also contributes to tissue damage during autoimmune and inflammatory diseases. Neutrophils express a large number of cell surface receptors for the recognition of pathogen invasion and the inflammatory environment. Those include G-protein-coupled chemokine and chemoattractant receptors, Fc-receptors, adhesion receptors such as selectins/selectin ligands and integrins, various cytokine receptors, as well as innate immune receptors such as Toll-like receptors and C-type lectins. The various cell surface receptors trigger very diverse signal transduction pathways including activation of heterotrimeric and monomeric G-proteins, receptor-induced and store-operated Ca2 + signals, protein and lipid kinases, adapter proteins and cytoskeletal rearrangement. Here we provide an overview of the receptors involved in neutrophil activation and the intracellular signal transduction processes they trigger. This knowledge is crucial for understanding how neutrophils participate in antimicrobial host defense and inflammatory tissue damage and may also point to possible future targets of the pharmacological therapy of neutrophil-mediated autoimmune or inflammatory diseases. PMID:23994464

Simple Motor Control Concept Results High Efficiency at High Velocities

NASA Astrophysics Data System (ADS)

Starin, Scott; Engel, Chris

2013-09-01

The need for high velocity motors in space applications for reaction wheels and detectors has stressed the limits of Brushless Permanent Magnet Motors (BPMM). Due to inherent hysteresis core losses, conventional BPMMs try to balance the need for torque verses hysteresis losses. Cong-less motors have significantly less hysteresis losses but suffer from lower efficiencies. Additionally, the inherent low inductance in cog-less motors result in high ripple currents or high switching frequencies, which lowers overall efficiency and increases performance demands on the control electronics.However, using a somewhat forgotten but fully qualified technology of Isotropic Magnet Motors (IMM), extremely high velocities may be achieved at low power input using conventional drive electronics. This paper will discuss the trade study efforts and empirical test data on a 34,000 RPM IMM.

Highly efficient and high-power diode-pumped femtosecond Yb:LYSO laser

NASA Astrophysics Data System (ADS)

Tian, Wenlong; Wang, Zhaohua; Zhu, Jiangfeng; Zheng, Lihe; Xu, Jun; Wei, Zhiyi

2017-04-01

A diode-pumped high-power femtosecond Yb:LYSO laser with high efficiency is demonstrated. With a semiconductor saturable absorber mirror for passive mode-locking and a Gires-Tournois interferometer mirror for intracavity dispersion compensation, stable mode-locking pulses of 297 fs duration at 1042 nm were obtained. The maximum average power of 3.07 W was realized under 5.17 W absorbed pump power, corresponding to as high as 59.4% opt-opt efficiency. The single pulse energy and peak power are about 35.5 nJ and 119.5 kW, respectively.

[The role of Smads and related transcription factors in the signal transduction of bone morphogenetic protein inducing bone formation].

PubMed

Xu, Xiao-liang; Dai, Ke-rong; Tang, Ting-ting

2003-09-01

To clarify the mechanisms of the signal transduction of bone morphogenetic proteins (BMPs) inducing bone formation and to provide theoretical basis for basic and applying research of BMPs. We looked up the literature of the role of Smads and related transcription factors in the signal transduction of BMPs inducing bone formation. The signal transduction processes of BMPs included: 1. BMPs combined with type II and type I receptors; 2. the type I receptor phosphorylated Smads; and 3. Smads entered the cell nucleus, interacted with transcription factors and influenced the transcription of related proteins. Smads could be divided into receptor-regulated Smads (R-Smads: Smad1, Smad2, Smad3, Smad5, Smad8 and Smad9), common-mediator Smad (co-Smad: Smad4), and inhibitory Smads (I-Smads: Smad6 and Smad7). Smad1, Smad5, Smad8, and probable Smad9 were involved in the signal transduction of BMPs. Multiple kinases, such as focal adhesion kinase (FAK), Ras-extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), and Akt serine/threonine kinase were related to Smads signal transduction. Smad1 and Smad5 related with transcription factors included core binding factor A1 (CBFA1), smad-interacting protein 1 (SIP1), ornithine decarboxylase antizyme (OAZ), activating protein-1 (AP-1), xenopus ventralizing homeobox protein-2 (Xvent-2), sandostatin (Ski), antiproliferative proteins (Tob), and homeodomain-containing transcriptian factor-8 (Hoxc-8), et al. CBFA1 could interact with Smad1, Smad2, Smad3, and Smad5, so it was involved in TGF-beta and BMP-2 signal transduction, and played an important role in the bone formation. Cleidocranial dysplasia (CCD) was thought to be caused by heterozygous mutations in CBFA1. The CBFA1 knockout mice showed no osteogenesis and had maturational disturbance of chondrocytes. Smads and related transcription factors, especially Smad1, Smad5, Smad8 and CBFA1, play an important role in the signal transduction of BMPs inducing bone

High efficiency III-nitride light-emitting diodes

DOEpatents

Crawford, Mary; Koleske, Daniel; Cho, Jaehee; Zhu, Di; Noemaun, Ahmed; Schubert, Martin F; Schubert, E. Fred

2013-05-28

Tailored doping of barrier layers enables balancing of the radiative recombination among the multiple-quantum-wells in III-Nitride light-emitting diodes. This tailored doping enables more symmetric carrier transport and uniform carrier distribution which help to reduce electron leakage and thus reduce the efficiency droop in high-power III-Nitride LEDs. Mitigation of the efficiency droop in III-Nitride LEDs may enable the pervasive market penetration of solid-state-lighting technologies in high-power lighting and illumination.

Defining a Novel Role for the Coxsackievirus and Adenovirus Receptor in Human Adenovirus Serotype 5 Transduction In Vitro in the Presence of Mouse Serum

PubMed Central

Lopez-Gordo, Estrella; Doszpoly, Andor; Duffy, Margaret R.; Coughlan, Lynda; Bradshaw, Angela C.; White, Katie M.; Denby, Laura; Nicklin, Stuart A.

2017-01-01

ABSTRACT Human adenoviral serotype 5 (HAdV-5) vectors have predominantly hepatic tropism when delivered intravascularly, resulting in immune activation and toxicity. Coagulation factor X (FX) binding to HAdV-5 mediates liver transduction and provides protection from virion neutralization in mice. FX is dispensable for liver transduction in mice lacking IgM antibodies or complement, suggesting that alternative transduction pathways exist. To identify novel factor(s) mediating HAdV-5 FX-independent entry, we investigated HAdV-5 transduction in vitro in the presence of serum from immunocompetent C57BL/6 or immunocompromised mice lacking IgM antibodies (Rag 2−/− and NOD-scid-gamma [NSG]). Sera from all three mouse strains enhanced HAdV-5 transduction of A549 cells. While inhibition of HAdV-5–FX interaction with FX-binding protein (X-bp) inhibited transduction in the presence of C57BL/6 serum, it had negligible effect on the enhanced transduction observed in the presence of Rag 2−/− or NSG serum. Rag 2−/− serum also enhanced transduction of the FX binding-deficient HAdV-5HVR5*HVR7*E451Q (AdT*). Interestingly, Rag 2−/− serum enhanced HAdV-5 transduction in a FX-independent manner in CHO-CAR and SKOV3-CAR cells (CHO or SKOV3 cells transfected to stably express human coxsackievirus and adenovirus receptor [CAR]). Additionally, blockade of CAR with soluble HAdV-5 fiber knob inhibited mouse serum-enhanced transduction in A549 cells, suggesting a potential role for CAR. Transduction of HAdV-5 KO1 and HAdV-5/F35 (CAR binding deficient) in the presence of Rag 2−/− serum was equivalent to that of HAdV-5, indicating that direct interaction between HAdV-5 and CAR is not required. These data suggest that FX may protect HAdV-5 from neutralization but has minimal contribution to HAdV-5 transduction in the presence of immunocompromised mouse serum. Alternatively, transduction occurs via an unidentified mouse serum protein capable of bridging HAdV-5 to CAR

Manipulating the membrane penetration mechanism of helical polypeptides via aromatic modification for efficient gene delivery.

PubMed

Zheng, Nan; Song, Ziyuan; Yang, Jiandong; Liu, Yang; Li, Fangfang; Cheng, Jianjun; Yin, Lichen

2017-08-01

The delivery performance of non-viral gene vectors is greatly related to their intracellular kinetics. Cationic helical polypeptides with potent membrane penetration properties and gene transfection efficiencies have been recently developed by us. However, they suffer from severe drawbacks in terms of their membrane penetration mechanisms that mainly include endocytosis and pore formation. The endocytosis mechanism leads to endosomal entrapment of gene cargos, while the charge- and helicity-induced pore formation causes appreciable cytotoxicity at high concentrations. With the attempt to overcome such critical challenges, we incorporated aromatic motifs into the design of helical polypeptides to enhance their membrane activities and more importantly, to manipulate their membrane penetration mechanisms. The aromatically modified polypeptides exhibited higher cellular internalization level than the unmodified analogue by up to 2.5 folds. Such improvement is possibly because aromatic domains promoted the polypeptides to penetrate cell membranes via direct transduction, a non-endocytosis and non-pore formation mechanism. As such, gene cargos were more efficiently delivered into cells by bypassing endocytosis and subsequently avoiding endosomal entrapment, and the material toxicity associated with excessive pore formation was also reduced. The top-performing aromatic polypeptide containing naphthyl side chains at the incorporated content of 20mol% revealed notably higher transfection efficiencies than commercial reagents in melanoma cells in vitro (by 11.7 folds) and in vivo (by 9.1 folds), and thus found potential utilities toward topical gene delivery for cancer therapy. Cationic helical polypeptides, as efficient gene delivery materials, suffer from severe drawbacks in terms of their membrane penetration mechanisms. The main cell penetration mechanisms involved are endocytosis and pore formation. However, the endocytosis mechanism has the limitation of endosomal

Thermophotonics for ultra-high efficiency visible LEDs

NASA Astrophysics Data System (ADS)

Ram, Rajeev J.

2017-02-01

The wall-plug efficiency of modern light-emitting diodes (LEDs) has far surpassed all other forms of lighting and is expected to improve further as the lifetime cost of a luminaire is today dominated by the cost of energy. The drive towards higher efficiency inevitably opens the question about the limits of future enhancement. Here, we investigate thermoelectric pumping as a means for improving efficiency in wide-bandgap GaN based LEDs. A forward biased diode can work as a heat pump, which pumps lattice heat into the electrons injected into the active region via the Peltier effect. We experimentally demonstrate a thermally enhanced 450 nm GaN LED, in which nearly fourfold light output power is achieved at 615 K (compared to 295 K room temperature operation), with virtually no reduction in the wall-plug efficiency at bias V < ℏω/q. This result suggests the possibility of removing bulky heat sinks in high power LED products. A review of recent high-efficiency GaN LEDs suggests that Peltier thermal pumping plays a more important role in a wide range of modern LED structures that previously thought - opening a path to even higher efficiencies and lower lifetime costs for future lighting.

Topology of an intracellular transduction chain (phototropism of Phycomyces): 1. Joint review of functional, temporal, and spatial aspects.

PubMed

Wenzler, D; Reinhardt, M; Fukshansky, L

2001-08-21

Two light-induced growth reactions in a unicellular cylindrical sporangiophore of Phycomyces blakesleeanus-vertical growth acceleration under symmetrical irradiation (photomecism) and directional growth under unilateral irradiation (phototropism)-share common input light perception as well as common output growth mechanism but have strongly divergent dynamics and other distinctive features. This divergence culminates in the phototropic paradoxes the main of which states that photomecism shows total adaptation, while phototropism does not adapt. The basis for this contradiction is that the phototropic transduction chain, unlike that of photomecism, faces a spatially non-uniform stimulus and processes a series of spatial patterns (light and absorption profiles, adaptation profile, etc.). The only way to resolve the paradoxes and correlate features of both responses within a single transduction chain is to assume non-local signal transduction, e.g. a cross-talk between different azimuthal locations within the cylindrical cell. On the other hand, to establish the presence of an appropriate cross-talk is equivalent of gaining insight into the topology of the transduction chain. This series of two papers contains a review reconsidering the entire field from this viewpoint (Paper 1) and a mathematical model of pattern transduction which unifies features of phototropism and resolves the paradoxes (Paper 2). At the same time, this is the first "proof of concept" for the "activity/pooling (a/p) networks"-a specific mathematical apparatus designed to analyse systemic properties and control in metabolic pathways. Copyright 2001 Academic Press.

Development and Characterization of High-Efficiency, High-Specific Impulse Xenon Hall Thrusters

NASA Technical Reports Server (NTRS)

Hofer, Richard R.; Jacobson, David (Technical Monitor)

2004-01-01

This dissertation presents research aimed at extending the efficient operation of 1600 s specific impulse Hall thruster technology to the 2000 to 3000 s range. Motivated by previous industry efforts and mission studies, the aim of this research was to develop and characterize xenon Hall thrusters capable of both high-specific impulse and high-efficiency operation. During the development phase, the laboratory-model NASA 173M Hall thrusters were designed and their performance and plasma characteristics were evaluated. Experiments with the NASA-173M version 1 (v1) validated the plasma lens magnetic field design. Experiments with the NASA 173M version 2 (v2) showed there was a minimum current density and optimum magnetic field topography at which efficiency monotonically increased with voltage. Comparison of the thrusters showed that efficiency can be optimized for specific impulse by varying the plasma lens. During the characterization phase, additional plasma properties of the NASA 173Mv2 were measured and a performance model was derived. Results from the model and experimental data showed how efficient operation at high-specific impulse was enabled through regulation of the electron current with the magnetic field. The electron Hall parameter was approximately constant with voltage, which confirmed efficient operation can be realized only over a limited range of Hall parameters.

Energy Transduction Inside of Amphiphilic Vesicles: Encapsulation of Photochemically Active Semiconducting Particles

NASA Astrophysics Data System (ADS)

Summers, David P.; Noveron, Juan; Basa, Ranor C. B.

2009-04-01

Amphiphilic bilayer membrane structures (vesicles) have been postulated to have been abiotically formed and spontaneously assemble on the prebiotic Earth, providing compartmentalization for the origin of life. These vesicles are similar to modern cellular membranes and can serve to contain water-soluble species, concentrate species, and have the potential to catalyze reactions. The origin of the use of photochemical energy in metabolism (i.e. energy transduction) is one of the central issues in the origin of life. This includes such questions as how energy transduction may have occurred before complex enzymatic systems, such as required by contemporary photosynthesis, had developed and how simple a photochemical system is possible. It has been postulated that vesicle structures developed the ability to capture and transduce light, providing energy for reactions. It has also been shown that pH gradients across the membrane surface can be photochemically created, but coupling these to drive chemical reactions has been difficult. Colloidal semiconducting mineral particles are known to photochemically drive redox chemistry. We propose that encapsulation of these particles has the potential to provide a source of energy transduction inside vesicles, and thereby drive protocellular chemistry, and represents a model system for early photosynthesis. In our experiments we show that TiO2 particles, in the ~20 nm size range, can be incorporated into vesicles and retain their photoactivity through the dehydration/rehydration cycles that have been shown to concentrate species inside a vesicle.

Energy transduction inside of amphiphilic vesicles: encapsulation of photochemically active semiconducting particles.

PubMed

Summers, David P; Noveron, Juan; Basa, Ranor C B

2009-04-01

Amphiphilic bilayer membrane structures (vesicles) have been postulated to have been abiotically formed and spontaneously assemble on the prebiotic Earth, providing compartmentalization for the origin of life. These vesicles are similar to modern cellular membranes and can serve to contain water-soluble species, concentrate species, and have the potential to catalyze reactions. The origin of the use of photochemical energy in metabolism (i.e. energy transduction) is one of the central issues in the origin of life. This includes such questions as how energy transduction may have occurred before complex enzymatic systems, such as required by contemporary photosynthesis, had developed and how simple a photochemical system is possible. It has been postulated that vesicle structures developed the ability to capture and transduce light, providing energy for reactions. It has also been shown that pH gradients across the membrane surface can be photochemically created, but coupling these to drive chemical reactions has been difficult. Colloidal semiconducting mineral particles are known to photochemically drive redox chemistry. We propose that encapsulation of these particles has the potential to provide a source of energy transduction inside vesicles, and thereby drive protocellular chemistry, and represents a model system for early photosynthesis. In our experiments we show that TiO2 particles, in the approximately 20 nm size range, can be incorporated into vesicles and retain their photoactivity through the dehydration/rehydration cycles that have been shown to concentrate species inside a vesicle.

Transduction of PEP-1-heme oxygenase-1 into insulin-producing INS-1 cells protects them against cytokine-induced cell death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Su Jin; Kang, Hyung Kyung; Song, Dong Keun

Pro-inflammatory cytokines play a crucial role in the destruction of pancreatic β-cells, thereby triggering the development of autoimmune diabetes mellitus. We recently developed a cell-permeable fusion protein, PEP-1-heme oxygenase-1 (PEP-1-HO-1) and investigated the anti-inflammatory effects in macrophage cells. In this study, we transduced PEP-1-HO-1 into INS-1 insulinoma cells and examined its protective effect against cytokine-induced cell death. PEP-1-HO-1 was successfully delivered into INS-1 cells in time- and dose-dependent manner and was maintained within the cells for at least 48 h. Pre-treatment with PEP-1-HO-1 increased the survival of INS-1 cells exposed to cytokine mixture (IL-1β, IFN-γ, and TNF-α) in a dose-dependent manner.more » PEP-1-HO-1 markedly decreased cytokine-induced production of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). These protective effects of PEP-1-HO-1 against cytokines were correlated with the changes in the levels of signaling mediators of inflammation (iNOS and COX-2) and cell apoptosis/survival (Bcl-2, Bax, caspase-3, PARP, JNK, and Akt). These results showed that the transduced PEP-1-HO-1 efficiently prevented cytokine-induced cell death of INS-1 cells by alleviating oxidative/nitrosative stresses and inflammation. Further, these results suggested that PEP-1-mediated HO-1 transduction may be a potential therapeutic strategy to prevent β-cell destruction in patients with autoimmune diabetes mellitus. - Highlights: • We showed that PEP-1-HO-1 was efficiently delivered into INS-1 cells. • Transduced PEP-1-HO-1 exerted a protective effect against cytokine-induced cell death. • Transduced PEP-1-HO-1 inhibited cytokine-induced ROS and NO accumulation. • PEP-1-HO-1 suppressed cytokine-induced expression of iNOS, COX-2, and Bax. • PEP-1-HO-1 transduction may be an efficient tool to prevent β-cell destruction.« less

Widespread and highly persistent gene transfer to the CNS by retrovirus vector in utero: implication for gene therapy to Krabbe disease.

PubMed

Shen, Jin-Song; Meng, Xing-Li; Yokoo, Takashi; Sakurai, Ken; Watabe, Kazuhiko; Ohashi, Toya; Eto, Yoshikatsu

2005-05-01

Brain-directed prenatal gene therapy may benefit some lysosomal storage diseases that affect the central nervous system (CNS) before birth. Our previous study showed that intrauterine introduction of recombinant adenoviruses into cerebral ventricles results in efficient gene transfer to the CNS in the mouse. However, transgene expression decreased with time due to the non-integrative property of adenoviral vectors. In this study, in order to obtain permanent gene transduction, we investigated the feasibility of retrovirus-mediated in utero gene transduction. Concentrated retrovirus encoding the LacZ gene was injected into the cerebral ventricles of the embryos of normal and twitcher mice (a murine model of Krabbe disease) at embryonic day 12. The distribution and maintenance of the transgene expression in the recipient brain were analyzed histochemically, biochemically and by the quantitative polymerase chain reaction method pre- and postnatally. Efficient and highly persistent gene transduction to the brain was achieved both in normal and the twitcher mouse. Transduced neurons, astrocytes and oligodendrocytes were distributed throughout the brain. The transduced LacZ gene, its transcript and protein expression in the brain were maintained for 14 months without decrement. In addition, gene transduction to multiple tissues other than the brain was also detected at low levels. This study suggests that brain-directed in utero gene transfer using retrovirus vector may be beneficial to the treatment of lysosomal storage diseases with severe brain damage early in life, such as Krabbe disease. Copyright (c) 2005 John Wiley & Sons, Ltd.

Highly efficient solid state magnetoelectric gyrators

NASA Astrophysics Data System (ADS)

Leung, Chung Ming; Zhuang, Xin; Friedrichs, Daniel; Li, Jiefang; Erickson, Robert W.; Laletin, V.; Popov, M.; Srinivasan, G.; Viehland, D.

2017-09-01

An enhancement in the power-conversion-efficiency (η) of a magneto-electric (ME) gyrator has been found by the use of Mn-substituted nickel zinc ferrite. A trilayer gyrator of Mn-doped Ni0.8Zn0.2Fe2O3 and Pb(Zr,Ti)O3 has η = 85% at low power conditions (˜20 mW/in3) and η ≥ 80% at high power conditions (˜5 W/in3). It works close to fundamental electromechanical resonance in both direct and converse modes. The value of η is by far the highest reported so far, which is due to the high mechanical quality factor (Qm) of the magnetostrictive ferrite. Such highly efficient ME gyrators with a significant power density could become important elements in power electronics, potentially replacing electromagnetic and piezoelectric transformers.

Cancer classification through filtering progressive transductive support vector machine based on gene expression data

NASA Astrophysics Data System (ADS)

Lu, Xinguo; Chen, Dan

2017-08-01

Traditional supervised classifiers neglect a large amount of data which not have sufficient follow-up information, only work with labeled data. Consequently, the small sample size limits the advancement of design appropriate classifier. In this paper, a transductive learning method which combined with the filtering strategy in transductive framework and progressive labeling strategy is addressed. The progressive labeling strategy does not need to consider the distribution of labeled samples to evaluate the distribution of unlabeled samples, can effective solve the problem of evaluate the proportion of positive and negative samples in work set. Our experiment result demonstrate that the proposed technique have great potential in cancer prediction based on gene expression.

Analysis and logical modeling of biological signaling transduction networks

NASA Astrophysics Data System (ADS)

Sun, Zhongyao

The study of network theory and its application span across a multitude of seemingly disparate fields of science and technology: computer science, biology, social science, linguistics, etc. It is the intrinsic similarities embedded in the entities and the way they interact with one another in these systems that link them together. In this dissertation, I present from both the aspect of theoretical analysis and the aspect of application three projects, which primarily focus on signal transduction networks in biology. In these projects, I assembled a network model through extensively perusing literature, performed model-based simulations and validation, analyzed network topology, and proposed a novel network measure. The application of network modeling to the system of stomatal opening in plants revealed a fundamental question about the process that has been left unanswered in decades. The novel measure of the redundancy of signal transduction networks with Boolean dynamics by calculating its maximum node-independent elementary signaling mode set accurately predicts the effect of single node knockout in such signaling processes. The three projects as an organic whole advance the understanding of a real system as well as the behavior of such network models, giving me an opportunity to take a glimpse at the dazzling facets of the immense world of network science.

Highly efficient fully transparent inverted OLEDs

NASA Astrophysics Data System (ADS)

Meyer, J.; Winkler, T.; Hamwi, S.; Schmale, S.; Kröger, M.; Görrn, P.; Johannes, H.-H.; Riedl, T.; Lang, E.; Becker, D.; Dobbertin, T.; Kowalsky, W.

2007-09-01

One of the unique selling propositions of OLEDs is their potential to realize highly transparent devices over the visible spectrum. This is because organic semiconductors provide a large Stokes-Shift and low intrinsic absorption losses. Hence, new areas of applications for displays and ambient lighting become accessible, for instance, the integration of OLEDs into the windshield or the ceiling of automobiles. The main challenge in the realization of fully transparent devices is the deposition of the top electrode. ITO is commonly used as transparent bottom anode in a conventional OLED. To obtain uniform light emission over the entire viewing angle and a low series resistance, a TCO such as ITO is desirable as top contact as well. However, sputter deposition of ITO on top of organic layers causes damage induced by high energetic particles and UV radiation. We have found an efficient process to protect the organic layers against the ITO rf magnetron deposition process of ITO for an inverted OLED (IOLED). The inverted structure allows the integration of OLEDs in more powerful n-channel transistors used in active matrix backplanes. Employing the green electrophosphorescent material Ir(ppy) 3 lead to IOLED with a current efficiency of 50 cd/A and power efficiency of 24 lm/W at 100 cd/m2. The average transmittance exceeds 80 % in the visible region. The on-set voltage for light emission is lower than 3 V. In addition, by vertical stacking we achieved a very high current efficiency of more than 70 cd/A for transparent IOLED.

High Efficiency, Low Emission Refrigeration System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fricke, Brian A.; Sharma, Vishaldeep

Supermarket refrigeration systems account for approximately 50% of supermarket energy use, placing this class of equipment among the highest energy consumers in the commercial building domain. In addition, the commonly used refrigeration system in supermarket applications is the multiplex direct expansion (DX) system, which is prone to refrigerant leaks due to its long lengths of refrigerant piping. This leakage reduces the efficiency of the system and increases the impact of the system on the environment. The high Global Warming Potential (GWP) of the hydrofluorocarbon (HFC) refrigerants commonly used in these systems, coupled with the large refrigerant charge and the highmore » refrigerant leakage rates leads to significant direct emissions of greenhouse gases into the atmosphere. Methods for reducing refrigerant leakage and energy consumption are available, but underutilized. Further work needs to be done to reduce costs of advanced system designs to improve market utilization. In addition, refrigeration system retrofits that result in reduced energy consumption are needed since the majority of applications address retrofits rather than new stores. The retrofit market is also of most concern since it involves large-volume refrigerant systems with high leak rates. Finally, alternative refrigerants for new and retrofit applications are needed to reduce emissions and reduce the impact on the environment. The objective of this Collaborative Research and Development Agreement (CRADA) between the Oak Ridge National Laboratory and Hill Phoenix is to develop a supermarket refrigeration system that reduces greenhouse gas emissions and has 25 to 30 percent lower energy consumption than existing systems. The outcomes of this project will include the design of a low emission, high efficiency commercial refrigeration system suitable for use in current U.S. supermarkets. In addition, a prototype low emission, high efficiency supermarket refrigeration system will be produced

Access to the odor world: olfactory receptors and their role for signal transduction in insects.

PubMed

Fleischer, Joerg; Pregitzer, Pablo; Breer, Heinz; Krieger, Jürgen

2018-02-01

The sense of smell enables insects to recognize and discriminate a broad range of volatile chemicals in their environment originating from prey, host plants and conspecifics. These olfactory cues are received by olfactory sensory neurons (OSNs) that relay information about food sources, oviposition sites and mates to the brain and thus elicit distinct odor-evoked behaviors. Research over the last decades has greatly advanced our knowledge concerning the molecular basis underlying the reception of odorous compounds and the mechanisms of signal transduction in OSNs. The emerging picture clearly indicates that OSNs of insects recognize odorants and pheromones by means of ligand-binding membrane proteins encoded by large and diverse families of receptor genes. In contrast, the mechanisms of the chemo-electrical transduction process are not fully understood; the present status suggests a contribution of ionotropic as well as metabotropic mechanisms. In this review, we will summarize current knowledge on the peripheral mechanisms of odor sensing in insects focusing on olfactory receptors and their specific role in the recognition and transduction of odorant and pheromone signals by OSNs.

Silicon-based highly-efficient fiber-to-waveguide coupler for high index contrast systems

NASA Astrophysics Data System (ADS)

Nguyen, Victor; Montalbo, Trisha; Manolatou, Christina; Agarwal, Anu; Hong, Ching-yin; Yasaitis, John; Kimerling, L. C.; Michel, Jurgen

2006-02-01

A coupler to efficiently transfer broadband light from a single-mode optical fiber to a single-mode high-index contrast waveguide has been fabricated on a silicon substrate. We utilized a novel coupling scheme, with a vertically asymmetric design consisting of a stepwise parabolic graded index profile combined with a horizontal taper, to simultaneously confine light in both directions. Coupling efficiency has been measured as a function of the device dimensions. The optimal coupling efficiency is achieved for structures whose length equals the focal distance of the graded index and whose input width is close to the mode field diameter of the fiber. The fabricated structure is compact, robust and highly efficient, with an insertion loss of 2.2dB at 1550nm. The coupler exhibits less than 1dB variation in coupling efficiency in the measured spectral range from 1520nmto1620nm. The lowest insertion loss of 1.9dB is measured at 1540nm. The coupler design offers highly efficient coupling for single mode waveguides of core indices up to 2.2.

Efficient, high-power, and radially polarized fiber laser

PubMed Central

Lin, Di; Xia, Kegui; Li, Jianlang; Li, Ruxin; Ueda, Ken-ichi; Li, Guoqiang; Li, Xiaojun

2017-01-01

We demonstrate an ytterbium-doped fiber laser that emits high-power radially polarized light efficiently. In this study, a photonic crystal grating (PCG) was used as a polarization-selective output coupler, and the power of the radially polarized laser reached 2.42 W with a slope efficiency of 45.9% and a polarization purity of 96%. The results reveal that the inclusion of the PCG mirror into the fiber laser are particularly promising for generating high-power radially polarized light efficiently in view of its many important applications. PMID:20596223

Highly efficient white OLEDs for lighting applications

NASA Astrophysics Data System (ADS)

Murano, Sven; Burghart, Markus; Birnstock, Jan; Wellmann, Philipp; Vehse, Martin; Werner, Ansgar; Canzler, Tobias; Stübinger, Thomas; He, Gufeng; Pfeiffer, Martin; Boerner, Herbert

2005-10-01

The use of organic light-emitting diodes (OLEDs) for large area general lighting purposes is gaining increasing interest during the recent years. Especially small molecule based OLEDs have already shown their potential for future applications. For white light emission OLEDs, power efficiencies exceeding that of incandescent bulbs could already be demonstrated, however additional improvements are needed to further mature the technology allowing for commercial applications as general purpose illuminating sources. Ultimately the efficiencies of fluorescent tubes should be reached or even excelled, a goal which could already be achieved in the past for green OLEDs.1 In this publication the authors will present highly efficient white OLEDs based on an intentional doping of the charge carrier transport layers and the usage of different state of the art emission principles. This presentation will compare white PIN-OLEDs based on phosphorescent emitters, fluorescent emitters and stacked OLEDs. It will be demonstrated that the reduction of the operating voltage by the use of intentionally doped transport layers leads to very high power efficiencies for white OLEDs, demonstrating power efficiencies of well above 20 lm/W @ 1000 cd/m2. The color rendering properties of the emitted light is very high and CRIs between 85 and 95 are achieved, therefore the requirements for standard applications in the field of lighting applications could be clearly fulfilled. The color coordinates of the light emission can be tuned within a wide range through the implementation of minor structural changes.

Direct and Retrograde Transduction of Nigral Neurons with AAV6, 8, and 9 and Intraneuronal Persistence of Viral Particles

PubMed Central

Aebischer, Patrick

2013-01-01

Abstract Recombinant adeno-associated viral (AAV) vectors of serotypes 6, 8, and 9 were characterized as tools for gene delivery to dopaminergic neurons in the substantia nigra for future gene therapeutic applications in Parkinson's disease. While vectors of all three serotypes transduced nigral dopaminergic neurons with equal efficiency when directly injected to the substantia nigra, AAV6 was clearly superior to AAV8 and AAV9 for retrograde transduction of nigral neurons after striatal delivery. For sequential transduction of nigral dopaminergic neurons, the combination of AAV9 with AAV6 proved to be more powerful than AAV8 with AAV6 or repeated AAV6 administration. Surprisingly, single-stranded viral genomes persisted in nigral dopaminergic neurons within cell bodies and axon terminals in the striatum, and intact assembled AAV capsid was enriched in nuclei of nigral neurons, 4 weeks after virus injections to the substantia nigra. 6-Hydroxydopamine (6-OHDA)–induced degeneration of dopaminergic neurons in the substantia nigra reduced the number of viral genomes in the striatum, in line with viral genome persistence in axon terminals. However, 6-OHDA–induced axonal degeneration did not induce any transsynaptic spread of AAV infection in the striatum. Therefore, the potential presence of viral particles in axons may not represent an important safety issue for AAV gene therapy applications in neurodegenerative diseases. PMID:23600720

A composite approach boosts transduction coefficients of piezoceramics for energy harvesting

NASA Astrophysics Data System (ADS)

Yu, Xiaole; Hou, Yudong; Zheng, Mupeng; Zhao, Haiyan; Zhu, Mankang

2018-03-01

Piezoelectric energy harvesting is a hotspot in the field of new energy, the core goal of which is to prepare piezoceramics with a high transduction coefficient (d33×g33). The traditional solid-solution design strategy usually causes the same variation trend of d33 and ɛr, resulting in a low d33×g33 value. In this work, a composite design strategy was proposed that uses PZN-PZT/ZnAl2O4 as an example. By introducing ZnAl2O4, which is nonferroelectric with low ɛr, to the PZN-PZT piezoelectric matrix, ɛr decreased rapidly while d33 remained relatively stable. This behavior was ascribed to the increase of Q33 caused by an interfacial effect facilitating the formation of micro-domain structure.

High Efficiency Carbon Nanotube Thread Antennas

NASA Astrophysics Data System (ADS)

Bengio, Elie; Senic, Damir; Taylor, Lauren; Tsentalovich, Dmitri; Chen, Peiyu; Holloway, Christopher; Novotny, David; Babakhani, Aydin; Long, Christopher; Booth, James; Orloff, Nathan; Pasquali, Matteo

Although previous research has explored the underlying theory of high-frequency behavior of carbon nanotubes (CNTs) and CNT bundles for antennas, there is a gap in the literature for direct experimental measurements of radiation efficiency. Here we report a novel measurement technique to accurately characterize the radiation efficiency of quarter-wavelength monopole antennas made from CNT thread. At medical device (1 GHz) and Wi-Fi (2.4 GHz) frequencies, we measured the highest absolute values of radiation efficiency in the literature for CNT antennas, matching that of copper wire. We also report the first direct experimental observation that, contrary to metals, the radiation efficiency of the CNT thread improves significantly at higher frequencies. These results pave the way for practical applications of CNT thread antennas, particularly in the aerospace and wearable electronics industries where weight saving is a priority.

High efficiency tantalum-based ceramic composite structures

NASA Technical Reports Server (NTRS)

Stewart, David A. (Inventor); Leiser, Daniel B. (Inventor); DiFiore, Robert R. (Inventor); Katvala, Victor W. (Inventor)

2010-01-01

Tantalum-based ceramics are suitable for use in thermal protection systems. These composite structures have high efficiency surfaces (low catalytic efficiency and high emittance), thereby reducing heat flux to a spacecraft during planetary re-entry. These ceramics contain tantalum disilicide, molybdenum disilicide and borosilicate glass. The components are milled, along with a processing aid, then applied to a surface of a porous substrate, such as a fibrous silica or carbon substrate. Following application, the coating is then sintered on the substrate. The composite structure is substantially impervious to hot gas penetration and capable of surviving high heat fluxes at temperatures approaching 3000.degree. F. and above.

High efficiency magnetic bearings

NASA Technical Reports Server (NTRS)

Studer, Philip A.; Jayaraman, Chaitanya P.; Anand, Davinder K.; Kirk, James A.

1993-01-01

Research activities concerning high efficiency permanent magnet plus electromagnet (PM/EM) pancake magnetic bearings at the University of Maryland are reported. A description of the construction and working of the magnetic bearing is provided. Next, parameters needed to describe the bearing are explained. Then, methods developed for the design and testing of magnetic bearings are summarized. Finally, a new magnetic bearing which allows active torque control in the off axes directions is discussed.

Measure Guideline. High Efficiency Natural Gas Furnaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brand, L.; Rose, W.

2012-10-01

This measure guideline covers installation of high-efficiency gas furnaces, including: when to install a high-efficiency gas furnace as a retrofit measure; how to identify and address risks; and the steps to be used in the selection and installation process. The guideline is written for Building America practitioners and HVAC contractors and installers. It includes a compilation of information provided by manufacturers, researchers, and the Department of Energy as well as recent research results from the Partnership for Advanced Residential Retrofit (PARR) Building America team.

Concepts for high efficient white OLEDs for lighting applications

NASA Astrophysics Data System (ADS)

Hunze, A.; Krause, R.; Seidel, S.; Weiss, O.; Kozlowski, F.; Schmid, G.; Meyer, J.; Kröger, M.; Johannes, H. H.; Kowalsky, W.; Dobbertin, T.

2007-09-01

Apart from usage of organic light emitting diodes for flat panel display applications OLEDs are a potential candidate for the next solid state lighting technology. One key parameter is the development of high efficient, stable white devices. To realize this goal there are different concepts. Especially by using highly efficient phosphorescent guest molecules doped into a suitable host material high efficiency values can be obtained. We started our investigations with a single dopant and extended this to a two phosphorescent emitter approach leading to a device with a high power efficiency of more than 25 lm/W @ 1000 cd/m2. The disadvantage of full phosphorescent device setups is that esp. blue phosphorescent emitters show an insufficient long-term stability. A possibility to overcome this problem is the usage of more stable fluorescent blue dopants, whereas, due to the fact that only singlet excitons can decay radiatively, the efficiency is lower. With a concept, proposed by Sun et al.1 in 2006, it is possible to manage the recombination zone and thus the contribution from the different dopants. With this approach stable white color coordinates with sufficient current efficiency values have been achieved.

Prediction and design of efficient exciplex emitters for high-efficiency, thermally activated delayed-fluorescence organic light-emitting diodes.

PubMed

Liu, Xiao-Ke; Chen, Zhan; Zheng, Cai-Jun; Liu, Chuan-Lin; Lee, Chun-Sing; Li, Fan; Ou, Xue-Mei; Zhang, Xiao-Hong

2015-04-08

High-efficiency, thermally activated delayed-fluorescence organic light-emitting diodes based on exciplex emitters are demonstrated. The best device, based on a TAPC:DPTPCz emitter, shows a high external quantum efficiency of 15.4%. Strategies for predicting and designing efficient exciplex emitters are also provided. This approach allow prediction and design of efficient exciplex emitters for achieving high-efficiency organic light-emitting diodes, for future use in displays and lighting applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simple Retrofit High-Efficiency Natural Gas Water Heater Field Test

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schoenbauer, Ben

High-performance water heaters are typically more time consuming and costly to install in retrofit applications, making high performance water heaters difficult to justify economically. However, recent advancements in high performance water heaters have targeted the retrofit market, simplifying installations and reducing costs. Four high efficiency natural gas water heaters designed specifically for retrofit applications were installed in single-family homes along with detailed monitoring systems to characterize their savings potential, their installed efficiencies, and their ability to meet household demands. The water heaters tested for this project were designed to improve the cost-effectiveness and increase market penetration of high efficiency watermore » heaters in the residential retrofit market. The retrofit high efficiency water heaters achieved their goal of reducing costs, maintaining savings potential and installed efficiency of other high efficiency water heaters, and meeting the necessary capacity in order to improve cost-effectiveness. However, the improvements were not sufficient to achieve simple paybacks of less than ten years for the incremental cost compared to a minimum efficiency heater. Significant changes would be necessary to reduce the simple payback to six years or less. Annual energy savings in the range of $200 would also reduce paybacks to less than six years. These energy savings would require either significantly higher fuel costs (greater than $1.50 per therm) or very high usage (around 120 gallons per day). For current incremental costs, the water heater efficiency would need to be similar to that of a heat pump water heater to deliver a six year payback.« less

Creation of High Efficient Firefly Luciferase

NASA Astrophysics Data System (ADS)

Nakatsu, Toru

Firefly emits visible yellow-green light. The bioluminescence reaction is carried out by the enzyme luciferase. The bioluminescence of luciferase is widely used as an excellent tool for monitoring gene expression, the measurement of the amount of ATP and in vivo imaging. Recently a study of the cancer metastasis is carried out by in vivo luminescence imaging system, because luminescence imaging is less toxic and more useful for long-term assay than fluorescence imaging by GFP. However the luminescence is much dimmer than fluorescence. Then bioluminescence imaging in living organisms demands the high efficient luciferase which emits near infrared lights or enhances the emission intensity. Here I introduce an idea for creating the high efficient luciferase based on the crystal structure.

High efficiency carbon nanotube thread antennas

NASA Astrophysics Data System (ADS)

Amram Bengio, E.; Senic, Damir; Taylor, Lauren W.; Tsentalovich, Dmitri E.; Chen, Peiyu; Holloway, Christopher L.; Babakhani, Aydin; Long, Christian J.; Novotny, David R.; Booth, James C.; Orloff, Nathan D.; Pasquali, Matteo

2017-10-01

Although previous research has explored the underlying theory of high-frequency behavior of carbon nanotubes (CNTs) and CNT bundles for antennas, there is a gap in the literature for direct experimental measurements of radiation efficiency. These measurements are crucial for any practical application of CNT materials in wireless communication. In this letter, we report a measurement technique to accurately characterize the radiation efficiency of λ/4 monopole antennas made from the CNT thread. We measure the highest absolute values of radiation efficiency for CNT antennas of any type, matching that of copper wire. To capture the weight savings, we propose a specific radiation efficiency metric and show that these CNT antennas exceed copper's performance by over an order of magnitude at 1 GHz and 2.4 GHz. We also report direct experimental observation that, contrary to metals, the radiation efficiency of the CNT thread improves significantly at higher frequencies. These results pave the way for practical applications of CNT thread antennas, particularly in the aerospace and wearable electronics industries where weight saving is a priority.

NREL Inks Technology Agreement for High Efficiency Multijunction Solar

Science.gov Websites

) multijunction solar cells. While high-efficiency multijunction solar cells are commonly used for space Devices is excited to now be commercializing IMM solar cells for high-performance space and UAV Cells | News | NREL Inks Technology Agreement for High Efficiency Multijunction Solar Cells

Advanced high efficiency wraparound contact solar cell

NASA Technical Reports Server (NTRS)

Scott-Monck, J. A.; Uno, F. M.; Thornhill, J. W.

1977-01-01

A significant advancement in the development of thin high efficiency wraparound contact silicon solar cells has been made by coupling space and terrestrial processing procedures. Although this new method for fabricating cells has not been completely reduced to practice, some of the initial cells have delivered over 20 mW/sq cm when tested at 25 C under AMO intensity. This approach not only yields high efficiency devices, but shows promise of allowing complete freedom of choice in both the location and size of the wraparound contact pad area.

Advanced high efficiency wraparound contact solar cell

NASA Technical Reports Server (NTRS)

Scott-Monck, J. A.; Uno, F. M.; Thornhill, J. W.

1977-01-01

A significant advancement in the development of thin high efficiency wraparound contact silicon solar cells has been made by coupling space and terrestrial processing procedures. Although this new method for fabricating cells has not been completely reduced to practice, some of the initial cells have delivered over 20 mW/sq cm when tested at 25 C under AMO intensity. This approach not only yields high efficiency devices, but shows promise of allowing complete freedom of choice in both the location and size of the wraparound contact pad area

Measure Guideline: High Efficiency Natural Gas Furnaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brand, L.; Rose, W.

2012-10-01

This Measure Guideline covers installation of high-efficiency gas furnaces. Topics covered include when to install a high-efficiency gas furnace as a retrofit measure, how to identify and address risks, and the steps to be used in the selection and installation process. The guideline is written for Building America practitioners and HVAC contractors and installers. It includes a compilation of information provided by manufacturers, researchers, and the Department of Energy as well as recent research results from the Partnership for Advanced Residential Retrofit (PARR) Building America team.

High Efficiency End-Pumped Ho:Tm:YLF Disk Amplifier

NASA Technical Reports Server (NTRS)

Yu, Jirong; Singh, Upendra N.; Petros, Mulugeta; Axenson, Theresa J.; Barnes, Norman P.

1999-01-01

Space based coherent lidar for global wind measurement requires an all solid state laser system with high energy, high efficiency and narrow linewidth that operates in the eye safe region. A Q-switched, diode pumped Ho:Tm:YLF 2 micrometer laser with output energy of as much as 125 mJ at 6 Hz with an optical-to-optical efficiency of 3% has been reported. Single frequency operation of the laser was achieved by injection seeding. The design of this laser is being incorporated into NASA's SPARCLE (SPAce Readiness Coherent Lidar Experiment) wind lidar mission. Laser output energy ranging from 500 mJ to 2 J is required for an operational space coherent lidar. We previously developed a high energy Ho:Tm:YLF master oscillator and side pumped power amplifier system and demonstrated a 600-mJ single frequency pulse at a repetition rate of 10 Hz. Although the output energy is high, the optical-to-optical efficiency is only about 2%. Designing a high energy, highly efficient, conductively cooled 2-micrometer laser remains a challenge. In this paper, the preliminary result of an end-pumped amplifier that has a potential to provide a factor 3 of improvement in the system efficiency is reported.

Taste transductions in taste receptor cells: basic tastes and moreover.

PubMed

Iwata, Shusuke; Yoshida, Ryusuke; Ninomiya, Yuzo

2014-01-01

In the oral cavity, taste receptor cells dedicate to detecting chemical compounds in foodstuffs and transmitting their signals to gustatory nerve fibers. Heretofore, five taste qualities (sweet, umami, bitter, salty and sour) are generally accepted as basic tastes. Each of these may have a specific role in the detection of nutritious and poisonous substances; sweet for carbohydrate sources of calories, umami for protein and amino acid contents, bitter for harmful compounds, salty for minerals and sour for ripeness of fruits and spoiled foods. Recent studies have revealed molecular mechanisms for reception and transduction of these five basic tastes. Sweet, umami and bitter tastes are mediated by G-protein coupled receptors (GPCRs) and second-messenger signaling cascades. Salty and sour tastes are mediated by channel-type receptors. In addition to five basic tastes, taste receptor cells may have the ability to detect fat taste, which is elicited by fatty acids, and calcium taste, which is elicited by calcium. Taste compounds eliciting either fat taste or calcium taste may be detected by specific GPCRs expressed in taste receptor cells. This review will focus on transduction mechanisms and cellular characteristics responsible for each of basic tastes, fat taste and calcium taste.

A low-power, high-efficiency Ka-band TWTA

NASA Astrophysics Data System (ADS)

Curren, Arthur N.; Dayton, James A., Jr.; Palmer, Raymond W.; Force, Dale A.; Tamashiro, Rodney N.; Wilson, John F.; Dombro, Louis; Harvey, Wayne L.

1992-03-01

NASA has developed a new class of Ka-band TWT amplifiers (TWTAs) which achieve their high efficiency/low power performance goals by means of an advanced dynamic velocity taper (DVT). The DVT is characterized by a continuous, nonlinear reduction in helix pitch from its initial synchronous value in the output section of the TWT to near the end of the helix. Another efficiency-maximizing feature is the inclusion of a multistage depressed collector employing oxygen-free, high-conductivity Cu electrodes treated for secondary electron emission suppression by means of ion bombardment. An efficiency of 43 percent is expected to be reached.

Gravitational Effects on Signal Transduction

NASA Technical Reports Server (NTRS)

Sytkowski, Arthur J.

1999-01-01

An understanding of the mechanisms by which individual cells perceive gravity and how these cells transduce and respond to gravitational stimuli is critical for the development of long-term manned space flight experiments. We now propose to use a well-characterized model erythroid cell system and to investigate gravitational perturbations of its erythropoietin (Epo) signaling pathway and gene regulation. Cells will be grown at 1-G and in simulated microgravity in the NASA Rotating Wall Vessel bioreactor (RWV). Cell growth and differentiation, the Epo-receptor, the protein kinase C pathway to the c-myc gene, and the protein phosphatase pathway to the c-myb gene will be studied and evaluated as reporters of gravitational stimuli. The results of these experiments will have impact on the problems of 1) gravitational sensing by individual cells, and 2) the anemia of space flight. This ground-based study also will serve as a Space Station Development Study in gravitational effects on intracellular signal transduction.

Energy efficient engine high-pressure turbine detailed design report

NASA Technical Reports Server (NTRS)

Thulin, R. D.; Howe, D. C.; Singer, I. D.

1982-01-01

The energy efficient engine high-pressure turbine is a single stage system based on technology advancements in the areas of aerodynamics, structures and materials to achieve high performance, low operating economics and durability commensurate with commercial service requirements. Low loss performance features combined with a low through-flow velocity approach results in a predicted efficiency of 88.8 for a flight propulsion system. Turbine airfoil durability goals are achieved through the use of advanced high-strength and high-temperature capability single crystal materials and effective cooling management. Overall, this design reflects a considerable extension in turbine technology that is applicable to future, energy efficient gas-turbine engines.

Energy efficiency indicators for high electric-load buildings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aebischer, Bernard; Balmer, Markus A.; Kinney, Satkartar

2003-06-01

Energy per unit of floor area is not an adequate indicator for energy efficiency in high electric-load buildings. For two activities, restaurants and computer centres, alternative indicators for energy efficiency are discussed.

High Efficiency Centrifugal Compressor for Rotorcraft Applications

NASA Technical Reports Server (NTRS)

Medic, Gorazd; Sharma, Om P.; Jongwook, Joo; Hardin, Larry W.; McCormick, Duane C.; Cousins, William T.; Lurie, Elizabeth A.; Shabbir, Aamir; Holley, Brian M.; Van Slooten, Paul R.

2017-01-01

A centrifugal compressor research effort conducted by United Technologies Research Center under NASA Research Announcement NNC08CB03C is documented. The objectives were to identify key technical barriers to advancing the aerodynamic performance of high-efficiency, high work factor, compact centrifugal compressor aft-stages for turboshaft engines; to acquire measurements needed to overcome the technical barriers and inform future designs; to design, fabricate, and test a new research compressor in which to acquire the requisite flow field data. A new High-Efficiency Centrifugal Compressor stage -- splittered impeller, splittered diffuser, 90 degree bend, and exit guide vanes -- with aerodynamically aggressive performance and configuration (compactness) goals were designed, fabricated, and subquently tested at the NASA Glenn Research Center.

Proteomic Analysis Reveals Coordinated Regulation of Anthocyanin Biosynthesis through Signal Transduction and Sugar Metabolism in Black Rice Leaf.

PubMed

Chen, Linghua; Huang, Yining; Xu, Ming; Cheng, Zuxin; Zheng, Jingui

2017-12-15

Black rice ( Oryza sativa L.) is considered to be a healthy food due to its high content of anthocyanins in the pericarp. The synthetic pathway of anthocyanins in black rice grains has been identified, however, the proteomic profile of leaves during grain development is still unclear. Here, isobaric Tags Relative and Absolute Quantification (iTRAQ) MS/MS was carried out to identify statistically significant changes of leaf proteome in the black rice during grain development. Throughout three sequential developmental stages, a total of 3562 proteins were detected and 24 functional proteins were differentially expressed 3-10 days after flowering (DAF). The detected proteins are known to be involved in various biological processes and most of these proteins were related to gene expression regulatory (33.3%), signal transduction (16.7%) and developmental regulation and hormone-like proteins (12.5%). The coordinated changes were consistent with changes in regulatory proteins playing a leading role in leaves during black rice grain development. This indicated that signal transduction between leaves and grains may have an important role in anthocyanin biosynthesis and accumulation during grain development of black rice. In addition, four identified up-regulated proteins associated with starch metabolism suggested that the remobilization of nutrients for starch synthesis plays a potential role in anthocyanin biosynthesis of grain. The mRNA transcription for eight selected proteins was validated with quantitative real-time PCR. Our results explored the proteomics of the coordination between leaf and grain in anthocyanins biosynthesis of grain, which might be regulated by signal transduction and sugar metabolism in black rice leaf.

Proteomic Analysis Reveals Coordinated Regulation of Anthocyanin Biosynthesis through Signal Transduction and Sugar Metabolism in Black Rice Leaf

PubMed Central

Chen, Linghua; Huang, Yining; Xu, Ming; Cheng, Zuxin; Zheng, Jingui

2017-01-01

Black rice (Oryza sativa L.) is considered to be a healthy food due to its high content of anthocyanins in the pericarp. The synthetic pathway of anthocyanins in black rice grains has been identified, however, the proteomic profile of leaves during grain development is still unclear. Here, isobaric Tags Relative and Absolute Quantification (iTRAQ) MS/MS was carried out to identify statistically significant changes of leaf proteome in the black rice during grain development. Throughout three sequential developmental stages, a total of 3562 proteins were detected and 24 functional proteins were differentially expressed 3–10 days after flowering (DAF). The detected proteins are known to be involved in various biological processes and most of these proteins were related to gene expression regulatory (33.3%), signal transduction (16.7%) and developmental regulation and hormone-like proteins (12.5%). The coordinated changes were consistent with changes in regulatory proteins playing a leading role in leaves during black rice grain development. This indicated that signal transduction between leaves and grains may have an important role in anthocyanin biosynthesis and accumulation during grain development of black rice. In addition, four identified up-regulated proteins associated with starch metabolism suggested that the remobilization of nutrients for starch synthesis plays a potential role in anthocyanin biosynthesis of grain. The mRNA transcription for eight selected proteins was validated with quantitative real-time PCR. Our results explored the proteomics of the coordination between leaf and grain in anthocyanins biosynthesis of grain, which might be regulated by signal transduction and sugar metabolism in black rice leaf. PMID:29244752

High efficiency solar photovoltaic power module concept

NASA Technical Reports Server (NTRS)

Bekey, I.

1978-01-01

The investigation of a preliminary concept for high efficiency solar power generation in space is presented. The concept was a synergistic combination of spectral splitting, tailored bandgap cells, high concentration ratios, and cool cell areas.

Creating a bio-hybrid signal transduction pathway: opening a new channel of communication between cells and machines.

PubMed

Yarkoni, Orr; Donlon, Lynn; Frankel, Daniel

2012-12-01

Manipulation of signal transduction pathways presents a viable mechanism to interface cells with electronics. In this work, we present a two-step signal transduction pathway involving cellular and electronic transduction elements. In order to circumvent many of the conventional difficulties encountered when harnessing chemical signalling for the purpose of electronics communication, gaseous nitric oxide (NO) was selected as the signalling molecule. By genetic engineering of the nitric oxide synthase protein eNOS and insertion of light-oxygen-voltage (LOV) domains, we have created a photoactive version of the protein. The novel chimeric eNOS was found to be capable of producing NO in response to excitation by visible light. By coupling these mutant cells to a surface modified platinum electrode, it was possible to convert an optical signal into a chemical one, followed by subsequent conversion of the chemical signal into an electrical output.

Delta-Tocotrienol: Radiation Protection and Effects on Signal Transduction Pathways

DTIC Science & Technology

2011-06-15

Delta- Tocotrienol : Radiation Protection and Effects on Signal Transduction Pathways Venkataraman Srinivasan, PhD Mang Xiao, MD Principal...2011 2. REPORT TYPE 3. DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE Delta- Tocotrienol : Radiation Protection And Effects On...Mechanisms? 17 Survival of γ-irradiated mouse bone marrow and primary human hematopoietic CD34+ cells was significantly enhanced by Delta- tocotrienol (DT3

High transduction efficiency of circulating first trimester fetal mesenchymal stem cells: potential targets for in utero ex vivo gene therapy.

PubMed

Campagnoli, Cesare; Bellantuono, Ilaria; Kumar, Sailesh; Fairbairn, Leslie J; Roberts, Irene; Fisk, Nicholas M

2002-08-01

We recently reported the existence of fetal mesenchymal stem cells in first trimester fetal blood. Here we demonstrate that fetal mesenchymal stem cells from as early as eight weeks of gestation can be retrovirally transduced with 99% efficiency without selection. Circulating fetal mesenchymal stem cells are known to readily expand and differentiate into multiple tissue types both in vitro and in vivo, and might be suitable vehicles for prenatal gene delivery. With advances in early fetal blood sampling techniques, we suggest that genetic disorders causing irreversible damage before birth could be treated in utero in the late first/early second trimester by genetically manipulated autologous fetal stem cells.

TRYPTOPHAN SYNTHETASE LEVELS IN ESCHERICHIA COLI, SHIGELLA DYSENTERIAE, AND TRANSDUCTION HYBRIDS

PubMed Central

Eisenstein, Richard B.; Yanofsky, Charles

1962-01-01

Eisenstein, Richard B. (Western Reserve University, Cleveland, Ohio) and Charles Yanofsky. Tryptophan synthetase levels in Escherichia coli, Shigella dysenteriae, and transduction hybrids. J. Bacteriol. 83:193–204. 1962—Shigella dysenteriae and Escherichia coli, strains K-12 and B, were found to produce low levels of tryptophan synthetase, although some hybrids, formed by the introduction of the gene cluster concerned with tryptophan synthesis from S. dysenteriae into E. coli, produced high levels of this enzyme system. A revertant obtained from a tryptophan-requiring mutant also formed high levels of tryptophan synthetase. The gene or genes responsible for high enzyme production in these strains was shown to be linked to the cluster of genes concerned with tryptophan synthesis. The cause of high enzyme production was investigated. Various lines of evidence, including stimulation of growth by tryptophan precursors, sensitivity to inhibition by 5-methyltryptophan, absence of accumulation of tryptophan, and repression of enzyme formation by anthranilic acid and tryptophan, suggested that high enzyme production in the strains examined results from a partial block in the tryptophan pathway and not from resistance to repression by tryptophan. The conversion of shikimic acid-5-phosphate to anthranilic acid appears to be the partially blocked reaction in the strains studied. PMID:13889700

Flexible, highly efficient all-polymer solar cells

PubMed Central

Kim, Taesu; Kim, Jae-Han; Kang, Tae Eui; Lee, Changyeon; Kang, Hyunbum; Shin, Minkwan; Wang, Cheng; Ma, Biwu; Jeong, Unyong; Kim, Taek-Soo; Kim, Bumjoon J.

2015-01-01

All-polymer solar cells have shown great potential as flexible and portable power generators. These devices should offer good mechanical endurance with high power-conversion efficiency for viability in commercial applications. In this work, we develop highly efficient and mechanically robust all-polymer solar cells that are based on the PBDTTTPD polymer donor and the P(NDI2HD-T) polymer acceptor. These systems exhibit high power-conversion efficiency of 6.64%. Also, the proposed all-polymer solar cells have even better performance than the control polymer-fullerene devices with phenyl-C61-butyric acid methyl ester (PCBM) as the electron acceptor (6.12%). More importantly, our all-polymer solar cells exhibit dramatically enhanced strength and flexibility compared with polymer/PCBM devices, with 60- and 470-fold improvements in elongation at break and toughness, respectively. The superior mechanical properties of all-polymer solar cells afford greater tolerance to severe deformations than conventional polymer-fullerene solar cells, making them much better candidates for applications in flexible and portable devices. PMID:26449658

Status and Progress of High-efficiency Silicon Solar Cells

NASA Astrophysics Data System (ADS)

Xiao, Shaoqing; Xu, Shuyan

High-efficiency Si solar cells have attracted more and more attention from researchers, scientists, engineers of photovoltaic (PV) industry for the past few decades. Many high-quality researchers and engineers in both academia and industry seek solutions to improve the cell efficiency and reduce the cost. This desire has stimulated a growing number of major research and research infrastructure programmes, and a rapidly increasing number of publications in this filed. This chapter reviews materials, devices and physics of high-efficiency Si solar cells developed over the last 20 years. In this chapter there is a fair number of topics, not only from the material viewpoint, introducing various materials that are required for high-efficiency Si solar cells, such as base materials (FZ-Si, CZ-Si, MCZ-Si and multi-Si), emitter materials (diffused emitter and deposited emitter), passivation materials (Al-back surface field, high-low junction, SiO2, SiO x , SiN x , Al2O3 and a-Si:H), and other functional materials (antireflective layer, TCO and metal electrode), but also from the device and physics point of view, elaborating on physics, cell concept, development and status of all kinds of high-efficiency Si solar cells, such as passivated emitter and rear contact (PERC), passivated emitter and rear locally diffused (PERL), passivated emitter and rear totally diffused (PERT), Pluto, interdigitated back-contacted (IBC), emitter-wrap-through (EWT), metallization-wrap-through (MWT), Heterojunction with intrinsic thin-layer (HIT) and so on. Some representative examples of high-efficiency Si solar cell materials and devices with excellent performance and competitive advantages are presented.

Thermal modeling of high efficiency AMTEC cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ivanenok, J.F. III; Sievers, R.K.; Crowley, C.J.

1995-12-31

Remotely condensed Alkali Metal Thermal to Electric Conversion (AMTEC) cells achieve high efficiency by thermally isolating the hot {beta} Alumina Solid Electrolyte (BASE) tube from the cold condensing region. In order to design high efficiency AMTEC cells the designer must understand the heat losses associated with the AMTEC process. The major parasitic heat losses are due to conduction and radiation, and significant coupling of the two mechanisms occurs. This paper describes an effort to characterize the thermal aspects of the model PL-6 AMTEC cell and apply this understanding to the design of a higher efficiency AMTEC cell, model PL-8. Twomore » parallel analyses were used to model the thermal characteristics of PL-6. The first was a lumped node model using the classical electric circuit analogy and the second was a detailed finite-difference model. The lumped node model provides high speed and reasonable accuracy, and the detailed finite-difference model provides a more accurate, as well as visual, description of the cell temperature profiles. The results of the two methods are compared to the as-measured PL-6 data. PL-6 was the first cell to use a micromachined condenser to lower the radiation losses to the condenser, and it achieved a conversion efficiency of 15% (3 W output/20 W Input) at a temperature of 1050 K.« less

High efficiency photoionization detector

DOEpatents

Anderson, David F.

1984-01-01

A high efficiency photoionization detector using tetraaminoethylenes in a gaseous state having a low ionization potential and a relative photoionization cross section which closely matches the emission spectrum of xenon gas. Imaging proportional counters are also disclosed using the novel photoionization detector of the invention. The compound of greatest interest is TMAE which comprises tetrakis(dimethylamino)ethylene which has a measured ionization potential of 5.36.+-.0.02 eV, and a vapor pressure of 0.35 torr at 20.degree. C.

Molecular mechanisms of root gravity sensing and signal transduction.

PubMed

Strohm, Allison K; Baldwin, Katherine L; Masson, Patrick H

2012-01-01

Plants use gravity as a guide to direct their roots down into the soil to anchor themselves and to find resources needed for growth and development. In higher plants, the columella cells of the root tip form the primary site of gravity sensing, and in these cells the sedimentation of dense, starch-filled plastids (amyloplasts) triggers gravity signal transduction. This generates an auxin gradient across the root cap that is transmitted to the elongation zone where it promotes differential cell elongation, allowing the root to direct itself downward. It is still not well understood how amyloplast sedimentation leads to auxin redistribution. Models have been proposed to explain how mechanosensitive ion channels or ligand-receptor interactions could connect these events. Although their roles are still unclear, possible second messengers in this process include protons, Ca(2+), and inositol 1,4,5-triphosphate. Upon gravistimulation, the auxin efflux facilitators PIN3 and PIN7 relocalize to the lower side of the columella cells and mediate auxin redistribution. However, evidence for an auxin-independent secondary mechanism of gravity sensing and signal transduction suggests that this physiological process is quite complex. Furthermore, plants must integrate a variety of environmental cues, resulting in multifaceted relationships between gravitropism and other directional growth responses such as hydro-, photo-, and thigmotropism. Copyright © 2011 Wiley Periodicals, Inc.

A review of high-efficiency silicon solar cells

NASA Technical Reports Server (NTRS)

Rohatgi, A.

1986-01-01

Various parameters that affect solar cell efficiency were discussed. It is not understood why solar cells produced from less expensive Czochralski (Cz) silicon are less efficient than cells fabricated from more expensive float-zone (Fz) silicon. Performance characteristics were presented for recently produced, high-efficient solar cells fabricated by Westinghouse Electric Corp., Spire Corp., University of New South Wales, and Stanford University.

High probability neurotransmitter release sites represent an energy efficient design

PubMed Central

Lu, Zhongmin; Chouhan, Amit K.; Borycz, Jolanta A.; Lu, Zhiyuan; Rossano, Adam J; Brain, Keith L.; Zhou, You; Meinertzhagen, Ian A.; Macleod, Gregory T.

2016-01-01

Nerve terminals contain multiple sites specialized for the release of neurotransmitters. Release usually occurs with low probability, a design thought to confer many advantages. High probability release sites are not uncommon but their advantages are not well understood. Here we test the hypothesis that high probability release sites represent an energy efficient design. We examined release site probabilities and energy efficiency at the terminals of two glutamatergic motor neurons synapsing on the same muscle fiber in Drosophila larvae. Through electrophysiological and ultrastructural measurements we calculated release site probabilities to differ considerably between terminals (0.33 vs. 0.11). We estimated the energy required to release and recycle glutamate from the same measurements. The energy required to remove calcium and sodium ions subsequent to nerve excitation was estimated through microfluorimetric and morphological measurements. We calculated energy efficiency as the number of glutamate molecules released per ATP molecule hydrolyzed, and high probability release site terminals were found to be more efficient (0.13 vs. 0.06). Our analytical model indicates that energy efficiency is optimal (~0.15) at high release site probabilities (~0.76). As limitations in energy supply constrain neural function, high probability release sites might ameliorate such constraints by demanding less energy. Energy efficiency can be viewed as one aspect of nerve terminal function, in balance with others, because high efficiency terminals depress significantly during episodic bursts of activity. PMID:27593375

Plane Wave SH₀ Piezoceramic Transduction Optimized Using Geometrical Parameters.

PubMed

Boivin, Guillaume; Viens, Martin; Belanger, Pierre

2018-02-10

Structural health monitoring is a prominent alternative to the scheduled maintenance of safety-critical components. The nondispersive nature as well as the through-thickness mode shape of the fundamental shear horizontal guided wave mode (SH 0 ) make it a particularly attractive candidate for ultrasonic guided wave structural health monitoring. However, plane wave excitation of SH 0 at a high level of purity remains challenging because of the existence of the fundamental Lamb modes (A 0 and S 0 ) below the cutoff frequency thickness product of high-order modes. This paper presents a piezoelectric transducer concept optimized for plane SH 0 wave transduction based on the transducer geometry. The transducer parameter exploration was initially performed using a simple analytical model. A 3D multiphysics finite element model was then used to refine the transducer design. Finally, an experimental validation was conducted with a 3D laser Doppler vibrometer system. The analytical model, the finite element model, and the experimental measurement showed excellent agreement. The modal selectivity of SH 0 within a 20 ∘ beam opening angle at the design frequency of 425 kHz in a 1.59 mm aluminum plate was 23 dB, and the angle of the 6 dB wavefront was 86 ∘ .

Two-component signal transduction systems of Xanthomonas spp.: a lesson from genomics.

PubMed

Qian, Wei; Han, Zhong-Ji; He, Chaozu

2008-02-01

The two-component signal transduction systems (TCSTSs), consisting of a histidine kinase sensor (HK) and a response regulator (RR), are the dominant molecular mechanisms by which prokaryotes sense and respond to environmental stimuli. Genomes of Xanthomonas generally contain a large repertoire of TCSTS genes (approximately 92 to 121 for each genome), which encode diverse structural groups of HKs and RRs. Among them, although a core set of 70 TCSTS genes (about two-thirds in total) which accumulates point mutations with a slow rate are shared by these genomes, the other genes, especially hybrid HKs, experienced extensive genetic recombination, including genomic rearrangement, gene duplication, addition or deletion, and fusion or fission. The recombinations potentially promote the efficiency and complexity of TCSTSs in regulating gene expression. In addition, our analysis suggests that a co-evolutionary model, rather than a selfish operon model, is the major mechanism for the maintenance and microevolution of TCSTS genes in the genomes of Xanthomonas. Genomic annotation, secondary protein structure prediction, and comparative genomic analyses of TCSTS genes reviewed here provide insights into our understanding of signal networks in these important phytopathogenic bacteria.

Bacteriophage ϕMAM1, a Viunalikevirus, Is a Broad-Host-Range, High-Efficiency Generalized Transducer That Infects Environmental and Clinical Isolates of the Enterobacterial Genera Serratia and Kluyvera

PubMed Central

Matilla, Miguel A.

2014-01-01

Members of the enterobacterial genus Serratia are ecologically widespread, and some strains are opportunistic human pathogens. Bacteriophage ϕMAM1 was isolated on Serratia plymuthica A153, a biocontrol rhizosphere strain that produces the potently bioactive antifungal and anticancer haterumalide oocydin A. The ϕMAM1 phage is a generalized transducing phage that infects multiple environmental and clinical isolates of Serratia spp. and a rhizosphere strain of Kluyvera cryocrescens. Electron microscopy allowed classification of ϕMAM1 in the family Myoviridae. Bacteriophage ϕMAM1 is virulent, uses capsular polysaccharides as a receptor, and can transduce chromosomal markers at frequencies of up to 7 × 10−6 transductants per PFU. We also demonstrated transduction of the complete 77-kb oocydin A gene cluster and heterogeneric transduction of a plasmid carrying a type III toxin-antitoxin system. These results support the notion of the potential ecological importance of transducing phages in the acquisition of genes by horizontal gene transfer. Phylogenetic analyses grouped ϕMAM1 within the ViI-like bacteriophages, and genomic analyses revealed that the major differences between ϕMAM1 and other ViI-like phages arise in a region encoding the host recognition determinants. Our results predict that the wider genus of ViI-like phages could be efficient transducing phages, and this possibility has obvious implications for the ecology of horizontal gene transfer, bacterial functional genomics, and synthetic biology. PMID:25107968

New high-efficiency silicon solar cells

NASA Technical Reports Server (NTRS)

Daud, T.; Crotty, G. T.

1985-01-01

A design for silicon solar cells was investigated as an approach to increasing the cell open-circuit voltage and efficiency for flat-plate terrestrial photovoltaic applications. This deviates from past designs, where either the entire front surface of the cell is covered by a planar junction or the surface is textured before junction formation, which results in an even greater (up to 70%) junction area. The heavily doped front region and the junction space charge region are potential areas of high recombination for generated and injected minority carriers. The design presented reduces junction area by spreading equidiameter dot junctions across the surface of the cell, spaced about a diffusion length or less from each other. Various dot diameters and spacings allowed variations in total junction area. A simplified analysis was done to obtain a first-order design optimization. Efficiencies of up to 19% can be obtained. Cell fabrication involved extra masking steps for selective junction diffusion, and made surface passivation a key element in obtaining good collection. It also involved photolithography, with line widths down to microns. A method is demonstrated for achieving potentially high open-circuit voltages and solar-cell efficiencies.

Simple Retrofit High-Efficiency Natural Gas Water Heater Field Test

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schoenbauer, Ben

High performance water heaters are typically more time consuming and costly to install in retrofit applications, making high performance water heaters difficult to justify economically. However, recent advancements in high performance water heaters have targeted the retrofit market, simplifying installations and reducing costs. Four high efficiency natural gas water heaters designed specifically for retrofit applications were installed in single-family homes along with detailed monitoring systems to characterize their savings potential, their installed efficiencies, and their ability to meet household demands. The water heaters tested for this project were designed to improve the cost-effectiveness and increase market penetration of high efficiencymore » water heaters in the residential retrofit market. The retrofit high efficiency water heaters achieved their goal of reducing costs, maintaining savings potential and installed efficiency of other high efficiency water heaters, and meeting the necessary capacity in order to improve cost-effectiveness. However, the improvements were not sufficient to achieve simple paybacks of less than ten years for the incremental cost compared to a minimum efficiency heater. Significant changes would be necessary to reduce the simple payback to six years or less. Annual energy savings in the range of $200 would also reduce paybacks to less than six years. These energy savings would require either significantly higher fuel costs (greater than $1.50 per therm) or very high usage (around 120 gallons per day). For current incremental costs, the water heater efficiency would need to be similar to that of a heat pump water heater to deliver a six year payback.« less

Metal–Dielectric Waveguides for High Efficiency Fluorescence Imaging

PubMed Central

Zhu, Liangfu; Zhang, Douguo; Wang, Ruxue; Wang, Pei; Ming, Hai; Badugu, Ramachandram; Du, Luping; Yuan, Xiaocong; Lakowicz, Joseph R.

2015-01-01

We demonstrate that Metal–Dielectric Waveguide structures (MDWs) with high efficiency of fluorescence coupling can be suitable as substrates for fluorescence imaging. This hybrid MDWs consists of a continuous metal film and a dielectric top layer. The optical modes sustaining inside this structure can be excited with a high numerical aperture (N.A) objective, and then focused into a virtual optical probe with high intensity, leading to efficient excitation of fluorophores deposited on top of the MDWs. The emitted fluorophores couple with the optical modes thus enabling the directional emission, which is verified by the back focal plane (BFP) imaging. These unique properties of MDWs have been adopted in a scanning laser confocal optical microscopy, and show the merit of high efficiency fluorescence imaging. MDWs can be easily fabricated by vapor deposition and/or spin coating, the silica surface of the MDWs is suitable for biomolecule tethering, and will offer new opportunities for cell biology and biophysics research. PMID:26525494

MicroRNA-133 modulates the β1-adrenergic receptor transduction cascade.

PubMed

Castaldi, Alessandra; Zaglia, Tania; Di Mauro, Vittoria; Carullo, Pierluigi; Viggiani, Giacomo; Borile, Giulia; Di Stefano, Barbara; Schiattarella, Gabriele Giacomo; Gualazzi, Maria Giovanna; Elia, Leonardo; Stirparo, Giuliano Giuseppe; Colorito, Maria Luisa; Pironti, Gianluigi; Kunderfranco, Paolo; Esposito, Giovanni; Bang, Marie-Louise; Mongillo, Marco; Condorelli, Gianluigi; Catalucci, Daniele

2014-07-07

The sympathetic nervous system plays a fundamental role in the regulation of myocardial function. During chronic pressure overload, overactivation of the sympathetic nervous system induces the release of catecholamines, which activate β-adrenergic receptors in cardiomyocytes and lead to increased heart rate and cardiac contractility. However, chronic stimulation of β-adrenergic receptors leads to impaired cardiac function, and β-blockers are widely used as therapeutic agents for the treatment of cardiac disease. MicroRNA-133 (miR-133) is highly expressed in the myocardium and is involved in controlling cardiac function through regulation of messenger RNA translation/stability. To determine whether miR-133 affects β-adrenergic receptor signaling during progression to heart failure. Based on bioinformatic analysis, β1-adrenergic receptor (β1AR) and other components of the β1AR signal transduction cascade, including adenylate cyclase VI and the catalytic subunit of the cAMP-dependent protein kinase A, were predicted as direct targets of miR-133 and subsequently validated by experimental studies. Consistently, cAMP accumulation and activation of downstream targets were repressed by miR-133 overexpression in both neonatal and adult cardiomyocytes following selective β1AR stimulation. Furthermore, gain-of-function and loss-of-function studies of miR-133 revealed its role in counteracting the deleterious apoptotic effects caused by chronic β1AR stimulation. This was confirmed in vivo using a novel cardiac-specific TetON-miR-133 inducible transgenic mouse model. When subjected to transaortic constriction, TetON-miR-133 inducible transgenic mice maintained cardiac performance and showed attenuated apoptosis and reduced fibrosis compared with control mice. miR-133 controls multiple components of the β1AR transduction cascade and is cardioprotective during heart failure. © 2014 American Heart Association, Inc.

Wide-Band, High-Quantum-Efficiency Photodetector

NASA Technical Reports Server (NTRS)

Jackson, Deborah; Wilson, Daniel; Stern, Jeffrey

2007-01-01

A design has been proposed for a photodetector that would exhibit a high quantum efficiency (as much as 90 percent) over a wide wavelength band, which would typically be centered at a wavelength of 1.55 m. This and similar photodetectors would afford a capability for detecting single photons - a capability that is needed for research in quantum optics as well as for the practical development of secure optical communication systems for distribution of quantum cryptographic keys. The proposed photodetector would be of the hot-electron, phonon-cooled, thin-film superconductor type. The superconducting film in this device would be a meandering strip of niobium nitride. In the proposed photodetector, the quantum efficiency would be increased through incorporation of optiA design has been proposed for a photodetector that would exhibit a high quantum efficiency (as much as 90 percent) over a wide wavelength band, which would typically be centered at a wavelength of 1.55 m. This and similar photodetectors would afford a capability for detecting single photons - a capability that is needed for research in quantum optics as well as for the practical development of secure optical communication systems for distribution of quantum cryptographic keys. The proposed photodetector would be of the hot-electron, phonon-cooled, thin-film superconductor type. The superconducting film in this device would be a meandering strip of niobium nitride. In the proposed photodetector, the quantum efficiency would be increased through incorporation of opti-

METHODS FOR STUDYING BACTERIAL GENE TRANSFER IN SOIL BY CONJUGATION AND TRANSDUCTION

EPA Science Inventory

The purpose of this document is to provide a series of protocols by which a trained technician can conduct studies on the transfer of genetic information by conjugation or transduction in soil, with emphasis on bacteria containing recombinant DNA. The level of the document is gea...

Metformin selectively targets redox control of complex I energy transduction.

PubMed

Cameron, Amy R; Logie, Lisa; Patel, Kashyap; Erhardt, Stefan; Bacon, Sandra; Middleton, Paul; Harthill, Jean; Forteath, Calum; Coats, Josh T; Kerr, Calum; Curry, Heather; Stewart, Derek; Sakamoto, Kei; Repiščák, Peter; Paterson, Martin J; Hassinen, Ilmo; McDougall, Gordon; Rena, Graham

2018-04-01

Many guanide-containing drugs are antihyperglycaemic but most exhibit toxicity, to the extent that only the biguanide metformin has enjoyed sustained clinical use. Here, we have isolated unique mitochondrial redox control properties of metformin that are likely to account for this difference. In primary hepatocytes and H4IIE hepatoma cells we found that antihyperglycaemic diguanides DG5-DG10 and the biguanide phenformin were up to 1000-fold more potent than metformin on cell signalling responses, gluconeogenic promoter expression and hepatocyte glucose production. Each drug inhibited cellular oxygen consumption similarly but there were marked differences in other respects. All diguanides and phenformin but not metformin inhibited NADH oxidation in submitochondrial particles, indicative of complex I inhibition, which also corresponded closely with dehydrogenase activity in living cells measured by WST-1. Consistent with these findings, in isolated mitochondria, DG8 but not metformin caused the NADH/NAD + couple to become more reduced over time and mitochondrial deterioration ensued, suggesting direct inhibition of complex I and mitochondrial toxicity of DG8. In contrast, metformin exerted a selective oxidation of the mitochondrial NADH/NAD + couple, without triggering mitochondrial deterioration. Together, our results suggest that metformin suppresses energy transduction by selectively inducing a state in complex I where redox and proton transfer domains are no longer efficiently coupled. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Mechanisms of signal transduction by ethylene: overlapping and non-overlapping signalling roles in a receptor family

PubMed Central

Shakeel, Samina N.; Wang, Xiaomin; Binder, Brad M.; Schaller, G. Eric

2013-01-01

The plant hormone ethylene regulates growth and development as well as responses to biotic and abiotic stresses. Over the last few decades, key elements involved in ethylene signal transduction have been identified through genetic approaches, these elements defining a pathway that extends from initial ethylene perception at the endoplasmic reticulum to changes in transcriptional regulation within the nucleus. Here, we present our current understanding of ethylene signal transduction, focusing on recent developments that support a model with overlapping and non-overlapping roles for members of the ethylene receptor family. We consider the evidence supporting this model for sub-functionalization within the receptor family, and then discuss mechanisms by which such a sub-functionalization may occur. To this end, we consider the importance of receptor interactions in modulating their signal output and how such interactions vary in the receptor family. In addition, we consider evidence indicating that ethylene signal output by the receptors involves both phosphorylation-dependent and phosphorylation-independent mechanisms. We conclude with a current model for signalling by the ethylene receptors placed within the overall context of ethylene signal transduction. PMID:23543258

Fyn is a redox sensor involved in solar ultraviolet light-induced signal transduction in skin carcinogenesis.

PubMed

Kim, J-E; Roh, E; Lee, M H; Yu, D H; Kim, D J; Lim, T-G; Jung, S K; Peng, C; Cho, Y-Y; Dickinson, S; Alberts, D; Bowden, G T; Einspahr, J; Stratton, S P; Curiel-Lewandrowski, C; Bode, A M; Lee, K W; Dong, Z

2016-08-04

Solar ultraviolet (UV) light is a major etiological factor in skin carcinogenesis, with solar UV-stimulated signal transduction inducing pathological changes and skin damage. The primary sensor of solar UV-induced cellular signaling has not been identified. We use an experimental system of solar simulated light (SSL) to mimic solar UV and we demonstrate that Fyn is a primary redox sensor involved in SSL-induced signal transduction. Reactive oxygen species (ROS) generated by SSL exposure directly oxidize Cys488 of Fyn, resulting in increased Fyn kinase activity. Fyn oxidation was increased in mouse skin after SSL exposure and Fyn-knockout mice formed larger and more tumors compared with Fyn wild-type mice when exposed to SSL for an extended period of time. Murine embryonic fibroblasts (MEFs) lacking Fyn and cells in which Fyn expression was knocked down were resistant to SSL-induced apoptosis. Furthermore, cells expressing mutant Fyn (C448A) were resistant to SSL-induced apoptosis. These findings suggest that Fyn acts as a regulatory nexus between solar UV, ROS and signal transduction during skin carcinogenesis.

Efficiency of the High Efficiency Total Absorption Spectrometer (HECTOR)

NASA Astrophysics Data System (ADS)

Sprowal, Zaire; Simon, Anna; Reingold, Craig; Spyrou, Artemis; Naqvi, Farheen; Dombos, Alexander; Palmisano, Alicia; Anderson, Tyler; Anderson, Samuel; Moylan, Shane; Seymour, Christopher; Skulski, Michael; Smith, Mallory K.; Strauss, Sabrina; Kolk, Byant Vande

2016-09-01

The p-process is a nucleosynthesis process that occurs in explosive environments such as type II and Ia supernovae and is responsible for production of heavy proton rich nuclei. Gamma rays emitted during these explosions induce several photo-disintegration reactions: (γ,n), (γ,p), and (γ , α). To study these interactions, the inverse of these reactions are measured experimentally. The High Efficiency TOtal absorption spectrometeR (HECTOR) at the University of Notre Dame was built for measuring these reactions. Standard gamma sources 60Co and 137Cs and known resonances in 27Al(p, γ)28Si reaction were used to experimentally determine HECTOR's summing efficiency. Here, the preliminary analysis will be presented and the results will be compared to the Geant4 simulation of the array. This work was supported by the National Science Foundation under the Grant Number PHYS-1614442.

High-efficiency organic glass scintillators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Patrick L.; Carlson, Joseph S.

A new family of neutron/gamma discriminating scintillators is disclosed that comprises stable organic glasses that may be melt-cast into transparent monoliths. These materials have been shown to provide light yields greater than solution-grown trans-stilbene crystals and efficient PSD capabilities when combined with 0.01 to 0.05% by weight of the total composition of a wavelength-shifting fluorophore. Photoluminescence measurements reveal fluorescence quantum yields that are 2 to 5 times greater than conventional plastic or liquid scintillator matrices, which accounts for the superior light yield of these glasses. The unique combination of high scintillation light-yields, efficient neutron/gamma PSD, and straightforward scale-up via melt-castingmore » distinguishes the developed organic glasses from existing scintillators.« less

Cellerator: extending a computer algebra system to include biochemical arrows for signal transduction simulations

NASA Technical Reports Server (NTRS)

Shapiro, Bruce E.; Levchenko, Andre; Meyerowitz, Elliot M.; Wold, Barbara J.; Mjolsness, Eric D.

2003-01-01

Cellerator describes single and multi-cellular signal transduction networks (STN) with a compact, optionally palette-driven, arrow-based notation to represent biochemical reactions and transcriptional activation. Multi-compartment systems are represented as graphs with STNs embedded in each node. Interactions include mass-action, enzymatic, allosteric and connectionist models. Reactions are translated into differential equations and can be solved numerically to generate predictive time courses or output as systems of equations that can be read by other programs. Cellerator simulations are fully extensible and portable to any operating system that supports Mathematica, and can be indefinitely nested within larger data structures to produce highly scaleable models.

Genome, Integration, and Transduction of a Novel Temperate Phage of Helicobacter pylori

PubMed Central

Luo, Cheng-Hung; Chiou, Pei-Yu; Yang, Chiou-Ying

2012-01-01

Helicobacter pylori is a common human pathogen that has been identified to be carcinogenic. This study isolated the temperate bacteriophage 1961P from the lysate of a clinical strain of H. pylori isolated in Taiwan. The bacteriophage has an icosahedral head and a short tail, typical of the Podoviridae family. Its double-stranded DNA genome is 26,836 bp long and has 33 open reading frames. Only 9 of the predicted proteins have homologs of known functions, while the remaining 24 are only similar to unknown proteins encoded by Helicobacter prophages and remnants. Analysis of sequences proximal to the phage-host junctions suggests that 1961P may integrate into the host chromosome via a mechanism similar to that of bacteriophage lambda. In addition, 1961P is capable of generalized transduction. To the best of our knowledge, this is the first report of the isolation, characterization, genome analysis, integration, and transduction of a Helicobacter pylori phage. PMID:22696647

Targeting signal transduction pathways of cancer stem cells for therapeutic opportunities of metastasis.

PubMed

Iqbal, Waqas; Alkarim, Saleh; AlHejin, Ahmed; Mukhtar, Hasan; Saini, Kulvinder S

2016-11-15

Tumor comprises of heterogeneous population of cells where not all the disseminated cancer cells have the prerogative and "in-build genetic cues" to form secondary tumors. Cells with stem like properties complemented by key signaling molecules clearly have shown to exhibit selective growth advantage to form tumors at distant metastatic sites. Thus, defining the role of cancer stem cells (CSC) in tumorigenesis and metastasis is emerging as a major thrust area for therapeutic intervention. Precise relationship and regulatory mechanisms operating in various signal transduction pathways during cancer dissemination, extravasation and angiogenesis still remain largely enigmatic. How the crosstalk amongst circulating tumor cells (CTC), epithelial mesenchymal transition (EMT) process and CSC is coordinated for initiating the metastasis at secondary tissues, and during cancer relapse could be of great therapeutic interest. The signal transduction mechanisms facilitating the dissemination, infiltration of CSC into blood stream, extravasations, progression of metastasis phenotype and angiogenesis, at distant organs, are the key pathologically important vulnerabilities being elucidated. Therefore, current new drug discovery focus has shifted towards finding "key driver genes" operating in parallel signaling pathways, during quiescence, survival and maintenance of stemness in CSC. Understanding these mechanisms could open new horizons for tackling the issue of cancer recurrence and metastasis-the cause of ~90% cancer associated mortality. To design futuristic & targeted therapies, we propose a multi-pronged strategy involving small molecules, RNA interference, vaccines, antibodies and other biotechnological modalities against CSC and the metastatic signal transduction cascade.

High efficiency photoionization detector

DOEpatents

Anderson, D.F.

1984-01-31

A high efficiency photoionization detector is described using tetraaminoethylenes in a gaseous state having a low ionization potential and a relative photoionization cross section which closely matches the emission spectrum of xenon gas. Imaging proportional counters are also disclosed using the novel photoionization detector of the invention. The compound of greatest interest is TMAE which comprises tetrakis(dimethylamino)ethylene which has a measured ionization potential of 5.36 [+-] 0.02 eV, and a vapor pressure of 0.35 torr at 20 C. 6 figs.

High-efficiency aperiodic two-dimensional high-contrast-grating hologram

NASA Astrophysics Data System (ADS)

Qiao, Pengfei; Zhu, Li; Chang-Hasnain, Connie J.

2016-03-01

High efficiency phase holograms are designed and implemented using aperiodic two-dimensional (2D) high-contrast gratings (HCGs). With our design algorithm and an in-house developed rigorous coupled-wave analysis (RCWA) package for periodic 2D HCGs, the structural parameters are obtained to achieve a full 360-degree phase-tuning range of the reflected or transmitted wave, while maintaining the power efficiency above 90%. For given far-field patterns or 3D objects to reconstruct, we can generate the near-field phase distribution through an iterative process. The aperiodic HCG phase plates we design for holograms are pixelated, and the local geometric parameters for each pixel to achieve desired phase alternation are extracted from our periodic HCG designs. Our aperiodic HCG holograms are simulated using the 3D finite-difference time-domain method. The simulation results confirm that the desired far-field patterns are successfully produced under illumination at the designed wavelength. The HCG holograms are implemented on the quartz wafers, using amorphous silicon as the high-index material. We propose HCG designs at both visible and infrared wavelengths, and our simulation confirms the reconstruction of 3D objects. The high-contrast gratings allow us to realize low-cost, compact, flat, and integrable holograms with sub-micrometer thicknesses.

White collar 2, a partner in blue-light signal transduction, controlling expression of light-regulated genes in Neurospora crassa.

PubMed Central

Linden, H; Macino, G

1997-01-01

A saturating genetic dissection of 'blind' mutants in Neurospora crassa has identified a total of two non-redundant loci (wc-1 and wc-2) each of which is required for blue-light perception/signal transduction. Previously, we demonstrated that WC1 is a putative zinc finger transcription factor able to bind specifically to a light-regulated promoter. Here, we present the cloning and characterization of the wc-2 gene. We demonstrate using mutation analysis and in vitro DNA-binding assays that WC2, the second partner of this light signal transduction system, encodes a functional zinc finger DNA-binding protein with putative PAS dimerization and transcription activation domains. This molecular genetic dissection of the second of two components of this light signal transduction system has enabled us to devise a model whereby WC1 and WC2 are proposed to interact via homologous PAS domains, bind to promoters of light-regulated genes and activate transcription. As such, this study provides the first insight into two co-operating partners in blue-light signal transduction in any organism and describes the molecular tools with which to dissect this enigmatic process. PMID:9009271

High-Order Dielectric Metasurfaces for High-Efficiency Polarization Beam Splitters and Optical Vortex Generators

NASA Astrophysics Data System (ADS)

Guo, Zhongyi; Zhu, Lie; Guo, Kai; Shen, Fei; Yin, Zhiping

2017-08-01

In this paper, a high-order dielectric metasurface based on silicon nanobrick array is proposed and investigated. By controlling the length and width of the nanobricks, the metasurfaces could supply two different incremental transmission phases for the X-linear-polarized (XLP) and Y-linear-polarized (YLP) light with extremely high efficiency over 88%. Based on the designed metasurface, two polarization beam splitters working in high-order diffraction modes have been designed successfully, which demonstrated a high transmitted efficiency. In addition, we have also designed two vortex-beam generators working in high-order diffraction modes to create vortex beams with the topological charges of 2 and 3. The employment of dielectric metasurfaces operating in high-order diffraction modes could pave the way for a variety of new ultra-efficient optical devices.

High-efficiency photovoltaic cells

DOEpatents

Yang, H.T.; Zehr, S.W.

1982-06-21

High efficiency solar converters comprised of a two cell, non-lattice matched, monolithic stacked semiconductor configuration using optimum pairs of cells having bandgaps in the range 1.6 to 1.7 eV and 0.95 to 1.1 eV, and a method of fabrication thereof, are disclosed. The high band gap subcells are fabricated using metal organic chemical vapor deposition (MOCVD), liquid phase epitaxy (LPE) or molecular beam epitaxy (MBE) to produce the required AlGaAs layers of optimized composition, thickness and doping to produce high performance, heteroface homojunction devices. The low bandgap subcells are similarly fabricated from AlGa(As)Sb compositions by LPE, MBE or MOCVD. These subcells are then coupled to form a monolithic structure by an appropriate bonding technique which also forms the required transparent intercell ohmic contact (IOC) between the two subcells. Improved ohmic contacts to the high bandgap semiconductor structure can be formed by vacuum evaporating to suitable metal or semiconductor materials which react during laser annealing to form a low bandgap semiconductor which provides a low contact resistance structure.

Modulators of Stomatal Lineage Signal Transduction Alter Membrane Contact Sites and Reveal Specialization among ERECTA Kinases.

PubMed

Ho, Chin-Min Kimmy; Paciorek, Tomasz; Abrash, Emily; Bergmann, Dominique C

2016-08-22

Signal transduction from a cell's surface to its interior requires dedicated signaling elements and a cellular environment conducive to signal propagation. Plant development, defense, and homeostasis rely on plasma membrane receptor-like kinases to perceive endogenous and environmental signals, but little is known about their immediate downstream targets and signaling modifiers. Using genetics, biochemistry, and live-cell imaging, we show that the VAP-RELATED SUPPRESSOR OF TMM (VST) family is required for ERECTA-mediated signaling in growth and cell-fate determination and reveal a role for ERECTA-LIKE2 in modulating signaling by its sister kinases. We show that VSTs are peripheral plasma membrane proteins that can form complexes with integral ER-membrane proteins, thereby potentially influencing the organization of the membrane milieu to promote efficient and differential signaling from the ERECTA-family members to their downstream intracellular targets. Copyright © 2016 Elsevier Inc. All rights reserved.

High Power Klystrons for Efficient Reliable High Power Amplifiers.

DTIC Science & Technology

1980-11-01

techniques to obtain high overall efficiency. One is second harmonic space charge bunching. This is a process whereby the fundamental and second harmonic...components of the space charge waves in the electron beam of a microwave tube are combined to produce more highly concentrated electron bunches raising the...the drift lengths to enhance the 2nd harmonic component in the space charge waves. The latter method was utilized in the VKC-7790. Computer

Highly efficient organic electroluminescent diodes realized by efficient charge balance with optimized electron and hole transport layers

NASA Astrophysics Data System (ADS)

Khan, M. A.; Xu, Wei; Wei, Fuxiang; Bai, Yu; Jiang, X. Y.; Zhang, Z. L.; Zhu, W. Q.

2007-11-01

Highly efficient organic electroluminescent devices (OLEDs) were developed based on 4,7-diphenyl-1, 10-phenanthroline (BPhen) as the electron transport layer (ETL), tris-(8-hydroxyquinoline) aluminum (Alq 3) as the emission layer (EML) and N,Ń-bis-[1-naphthy(-N,Ńdiphenyl-1,1'-biphenyl-4,4'-diamine)] (NPB) as the hole transport layer (HTL). The typical device structure was glass substrate/ ITO/ NPB/ Alq 3/ BPhen/ LiF/ Al. Since BPhen possesses a considerable high electron mobility of 5×10 -4 cm 2 V -1 s -1, devices with BPhen as ETL can realize an extremely high luminous efficiency. By optimizing the thickness of both HTL and ETL, we obtained a highly efficient OLED with a current efficiency of 6.80 cd/A and luminance of 1361 cd/m 2 at a current density of 20 mA/cm 2. This dramatic improvement in the current efficiency has been explained on the principle of charge balance.

Resonantly pumped high efficiency Ho:YAG laser.

PubMed

Shen, Ying-Jie; Yao, Bao-Quan; Duan, Xiao-Ming; Dai, Tong-Yu; Ju, You-Lun; Wang, Yue-Zhu

2012-11-20

High-efficient CW and Q-switched Ho:YAG lasers resonantly dual-end-pumped by two diode-pumped Tm:YLF lasers at 1908 nm were investigated. A maximum slope efficiency of 74.8% in CW operation as well as a maximum output power of 58.7 W at 83.2 W incident pump power was achieved, which corresponded to an optical-to-optical conversion efficiency of 70.6%. The maximum pulse energy of 2.94 mJ was achieved, with a 31 ns FWHM pulse width and a peak power of approximately 94.7 kW.

High Efficiency mm-Wave Transmitter Array

DTIC Science & Technology

2016-09-01

SECURITY CLASSIFICATION OF: High efficiency, high power transmitters integrated in silicon at 45, 94 and 138 GHz were developed. Our approach...employs CMOS-SOI and SiGe HBT unit amplifiers, power -combined in free-space using antenna arrays to attain high power levels. In the baseline approach...the-art were made. At 45GHz, a single CMOS chip produced an RF power of 630mW, which yielded an EIRP of 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND

Mechano-sensing and transduction by endothelial surface glycocalyx: composition, structure, and function

PubMed Central

Fu, Bingmei M.; Tarbell, John M.

2014-01-01

The endothelial cells (ECs) lining every blood vessel wall are constantly exposed to the mechanical forces generated by blood flow. The EC responses to these hemodynamic forces play a critical role in the homeostasis of the circulatory system. To ensure proper EC mechano-sensing and transduction, there are a variety of mechano-sensors and transducers that have been identified on the EC surface, intra- and trans-EC membrane and within the EC cytoskeleton. Among them, the most recent candidate is the endothelial surface glycocalyx (ESG), which is a matrix-like thin layer covering the luminal surface of the EC. It consists of various proteoglycans, glycosaminoglycans, and plasma proteins, and is close to other prominent EC mechano-sensors and transducers. The ESG thickness was found to be in the order of 0.1–1 μm by different visualization techniques and in different types of vessels. Detailed analysis on the electron microscopy (EM) images of the microvascular ESG revealed a quasi-periodic substructure with the ESG fiber diameter of 10–12 and 20 nm spacing between adjacent fibers. Atomic force microscopy and optical tweezers were applied to investigate the mechanical properties of the ESG on the cultured EC monolayers and in solutions. Enzymatic degradation of specific ESG glycosaminoglycan components was used to directly elucidate the role of the ESG in EC mechano-sensing and transduction by measuring the shear-induced productions of nitric oxide and prostacyclin, two characteristic responses of the ECs to the flow. The unique location, composition, and structure of the ESG determine its role in EC mechano-sensing and transduction. PMID:23401243

Bioblendstocks that Enable High Efficiency Engine Designs

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCormick, Robert L.; Fioroni, Gina M.; Ratcliff, Matthew A.

2016-11-03

The past decade has seen a high level of innovation in production of biofuels from sugar, lipid, and lignocellulose feedstocks. As discussed in several talks at this workshop, ethanol blends in the E25 to E50 range could enable more highly efficient spark-ignited (SI) engines. This is because of their knock resistance properties that include not only high research octane number (RON), but also charge cooling from high heat of vaporization, and high flame speed. Emerging alcohol fuels such as isobutanol or mixed alcohols have desirable properties such as reduced gasoline blend vapor pressure, but also have lower RON than ethanol.more » These fuels may be able to achieve the same knock resistance benefits, but likely will require higher blend levels or higher RON hydrocarbon blendstocks. A group of very high RON (>150) oxygenates such as dimethyl furan, methyl anisole, and related compounds are also produced from biomass. While providing no increase in charge cooling, their very high octane numbers may provide adequate knock resistance for future highly efficient SI engines. Given this range of options for highly knock resistant fuels there appears to be a critical need for a fuel knock resistance metric that includes effects of octane number, heat of vaporization, and potentially flame speed. Emerging diesel fuels include highly branched long-chain alkanes from hydroprocessing of fats and oils, as well as sugar-derived terpenoids. These have relatively high cetane number (CN), which may have some benefits in designing more efficient CI engines. Fast pyrolysis of biomass can produce diesel boiling range streams that are high in aromatic, oxygen and acid contents. Hydroprocessing can be applied to remove oxygen and consequently reduce acidity, however there are strong economic incentives to leave up to 2 wt% oxygen in the product. This oxygen will primarily be present as low CN alkyl phenols and aryl ethers. While these have high heating value, their presence in

Factorizing the motion sensitivity function into equivalent input noise and calculation efficiency.

PubMed

Allard, Rémy; Arleo, Angelo

2017-01-01

The photopic motion sensitivity function of the energy-based motion system is band-pass peaking around 8 Hz. Using an external noise paradigm to factorize the sensitivity into equivalent input noise and calculation efficiency, the present study investigated if the variation in photopic motion sensitivity as a function of the temporal frequency is due to a variation of equivalent input noise (e.g., early temporal filtering) or calculation efficiency (ability to select and integrate motion). For various temporal frequencies, contrast thresholds for a direction discrimination task were measured in presence and absence of noise. Up to 15 Hz, the sensitivity variation was mainly due to a variation of equivalent input noise and little variation in calculation efficiency was observed. The sensitivity fall-off at very high temporal frequencies (from 15 to 30 Hz) was due to a combination of a drop of calculation efficiency and a rise of equivalent input noise. A control experiment in which an artificial temporal integration was applied to the stimulus showed that an early temporal filter (generally assumed to affect equivalent input noise, not calculation efficiency) could impair both the calculation efficiency and equivalent input noise at very high temporal frequencies. We conclude that at the photopic luminance intensity tested, the variation of motion sensitivity as a function of the temporal frequency was mainly due to early temporal filtering, not to the ability to select and integrate motion. More specifically, we conclude that photopic motion sensitivity at high temporal frequencies is limited by internal noise occurring after the transduction process (i.e., neural noise), not by quantal noise resulting from the probabilistic absorption of photons by the photoreceptors as previously suggested.

High-efficiency crystalline silicon technology development

NASA Technical Reports Server (NTRS)

Prince, M. B.

1984-01-01

The rationale for pursuing high efficiency crystalline silicon technology research is discussed. Photovoltaic energy systems are reviewed as to their cost effectiveness and their competitiveness with other energy systems. The parameters of energy system life are listed and briefly reviewed.

A high-efficiency thermoelectric converter for space applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Metzger, J.D.; El-Genk, M.S.

1990-01-01

This paper presents a concept for using high-temperature superconducting materials in thermoelectric generators (SCTE) to produce electricity at conversion efficiencies approaching 50% of the Carrot efficiency. The SCTE generator is applicable to systems operating in temperature ranges of high-temperature superconducting materials and thus would be a low-grade converter. Operating in cryogenic temperature ranges provides the advantage of inherently increasing the limits of the Carrot efficiency. Potential applications are for systems operating in space where the ambient temperatures are in the cryogenic temperature range. The advantage of using high-temperature superconducting material in a thermoelectric converter is that it would significantly reducemore » or eliminate the Joule heating losses in a thermoelectric element. This paper investigates the system aspects and the material requirements of the SCTE converter concept, and presents a conceptual design and an application for a space power system.« less

A high-efficiency thermoelectric converter for space applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Metzger, J.D.; El-Genk, M.S.

1990-12-31

This paper presents a concept for using high-temperature superconducting materials in thermoelectric generators (SCTE) to produce electricity at conversion efficiencies approaching 50% of the Carrot efficiency. The SCTE generator is applicable to systems operating in temperature ranges of high-temperature superconducting materials and thus would be a low-grade converter. Operating in cryogenic temperature ranges provides the advantage of inherently increasing the limits of the Carrot efficiency. Potential applications are for systems operating in space where the ambient temperatures are in the cryogenic temperature range. The advantage of using high-temperature superconducting material in a thermoelectric converter is that it would significantly reducemore » or eliminate the Joule heating losses in a thermoelectric element. This paper investigates the system aspects and the material requirements of the SCTE converter concept, and presents a conceptual design and an application for a space power system.« less

Synthetic mRNA is a more reliable tool for the delivery of DNA-targeting proteins into the cell nucleus than fusion with a protein transduction domain.

PubMed

Leontovyc, Ivan; Habart, David; Loukotova, Sarka; Kosinova, Lucie; Kriz, Jan; Saudek, Frantisek; Koblas, Tomas

2017-01-01

Cell reprogramming requires efficient delivery of reprogramming transcription factors into the cell nucleus. Here, we compared the robustness and workload of two protein delivery methods that avoid the risk of genomic integration. The first method is based on fusion of the protein of interest to a protein transduction domain (PTD) for delivery across the membranes of target cells. The second method relies on de novo synthesis of the protein of interest inside the target cells utilizing synthetic mRNA (syn-mRNA) as a template. We established a Cre/lox reporter system in three different cell types derived from human (PANC-1, HEK293) and rat (BRIN-BD11) tissues and used Cre recombinase to model a protein of interest. The system allowed constitutive expression of red fluorescence protein (RFP), while green fluorescence protein (GFP) was expressed only after the genomic action of Cre recombinase. The efficiency of protein delivery into cell nuclei was quantified as the frequency of GFP+ cells in the total cell number. The PTD method showed good efficiency only in BRIN-BD11 cells (68%), whereas it failed in PANC-1 and HEK293 cells. By contrast, the syn-mRNA method was highly effective in all three cell types (29-71%). We conclude that using synthetic mRNA is a more robust and less labor-intensive approach than using the PTD-fusion alternative.

High-speed and high-efficiency travelling wave single-photon detectors embedded in nanophotonic circuits

PubMed Central

Pernice, W.H.P.; Schuck, C.; Minaeva, O.; Li, M.; Goltsman, G.N.; Sergienko, A.V.; Tang, H.X.

2012-01-01

Ultrafast, high-efficiency single-photon detectors are among the most sought-after elements in modern quantum optics and quantum communication. However, imperfect modal matching and finite photon absorption rates have usually limited their maximum attainable detection efficiency. Here we demonstrate superconducting nanowire detectors atop nanophotonic waveguides, which enable a drastic increase of the absorption length for incoming photons. This allows us to achieve high on-chip single-photon detection efficiency up to 91% at telecom wavelengths, repeatable across several fabricated chips. We also observe remarkably low dark count rates without significant compromise of the on-chip detection efficiency. The detectors are fully embedded in scalable silicon photonic circuits and provide ultrashort timing jitter of 18 ps. Exploiting this high temporal resolution, we demonstrate ballistic photon transport in silicon ring resonators. Our direct implementation of a high-performance single-photon detector on chip overcomes a major barrier in integrated quantum photonics. PMID:23271658

Load-induced modulation of signal transduction networks.

PubMed

Jiang, Peng; Ventura, Alejandra C; Sontag, Eduardo D; Merajver, Sofia D; Ninfa, Alexander J; Del Vecchio, Domitilla

2011-10-11

Biological signal transduction networks are commonly viewed as circuits that pass along information--in the process amplifying signals, enhancing sensitivity, or performing other signal-processing tasks--to transcriptional and other components. Here, we report on a "reverse-causality" phenomenon, which we call load-induced modulation. Through a combination of analytical and experimental tools, we discovered that signaling was modulated, in a surprising way, by downstream targets that receive the signal and, in doing so, apply what in physics is called a load. Specifically, we found that non-intuitive changes in response dynamics occurred for a covalent modification cycle when load was present. Loading altered the response time of a system, depending on whether the activity of one of the enzymes was maximal and the other was operating at its minimal rate or whether both enzymes were operating at submaximal rates. These two conditions, which we call "limit regime" and "intermediate regime," were associated with increased or decreased response times, respectively. The bandwidth, the range of frequency in which the system can process information, decreased in the presence of load, suggesting that downstream targets participate in establishing a balance between noise-filtering capabilities and a circuit's ability to process high-frequency stimulation. Nodes in a signaling network are not independent relay devices, but rather are modulated by their downstream targets.

Charge transport in highly efficient iridium cored electrophosphorescent dendrimers

NASA Astrophysics Data System (ADS)

Markham, Jonathan P. J.; Samuel, Ifor D. W.; Lo, Shih-Chun; Burn, Paul L.; Weiter, Martin; Bässler, Heinz

2004-01-01

Electrophosphorescent dendrimers are promising materials for highly efficient light-emitting diodes. They consist of a phosphorescent core onto which dendritic groups are attached. Here, we present an investigation into the optical and electronic properties of highly efficient phosphorescent dendrimers. The effect of dendrimer structure on charge transport and optical properties is studied using temperature-dependent charge-generation-layer time-of-flight measurements and current voltage (I-V) analysis. A model is used to explain trends seen in the I-V characteristics. We demonstrate that fine tuning the mobility by chemical structure is possible in these dendrimers and show that this can lead to highly efficient bilayer dendrimer light-emitting diodes with neat emissive layers. Power efficiencies of 20 lm/W were measured for devices containing a second-generation (G2) Ir(ppy)3 dendrimer with a 1,3,5-tris(2-N-phenylbenzimidazolyl)benzene electron transport layer.

Hypergravity signal transduction and gene expression in cultured mammalian cells

NASA Technical Reports Server (NTRS)

Kumei, Y.; Whitson, P. A.

1994-01-01

A number of studies have been conducted during space flight and with clinostats and centrifuges, suggesting that gravity effects the proliferation and differentiation of mammalian cells in vitro. However, little is known about the mechanisms by which mammalian cells respond to changes in gravitational stress. This paper summarizes studies designed to clarify the effects of hypergravity on the cultured human HeLa cells and to investigate the mechanism of hypergravity signal transduction in these cells.

On-chip optical transduction scheme for graphene nano-electro-mechanical systems in silicon-photonic platform

NASA Astrophysics Data System (ADS)

Dash, Aneesh; Selvaraja, S. K.; Naik, A. K.

2018-02-01

We present a scheme for on-chip optical transduction of strain and displacement of Graphene-based Nano-Electro-Mechanical Systems (NEMS). A detailed numerical study on the feasibility of three silicon-photonic integrated circuit configurations is presented: Mach-Zehnder Interferometer(MZI), micro-ring resonator and ring-loaded MZI. An index-sensing based technique using a Mach-Zehnder Interferometer loaded with a ring resonator with a moderate Q-factor of 2400 can yield a sensitivity of 28 fm/sqrt(Hz), and 6.5E-6 %/sqrt(Hz) for displacement and strain respectively. Though any phase sensitive integrated photonic device could be used for optical transduction, here we show that optimal sensitivity is achievable by combining resonance with phase sensitivity.

High efficiency compound semiconductor concentrator photovoltaics

NASA Technical Reports Server (NTRS)

Borden, P.; Gregory, P.; Saxena, R.; Owen, R.; Moore, O.

1980-01-01

Special emphasis was given to the high yield pilot production of packaged AlGaAs/GaAs concentrator solar cells, using organometallic VPE for materials growth, the demonstration of a concentrator module using 12 of these cells which achieved 16.4 percent conversion efficiency at 50 C coolant inlet temperature, and the demonstration of a spectral splitting converter module that achieved in excess of 20 percent efficiency. This converter employed ten silicon and ten AlGaAs cells with a dichroic filter functioning as the beam splitter. A monolithic array of AlGaAs/GaAs solar cells is described.

High-efficiency solar cell and method for fabrication

DOEpatents

Hou, Hong Q.; Reinhardt, Kitt C.

1999-01-01

A high-efficiency 3- or 4-junction solar cell is disclosed with a theoretical AM0 energy conversion efficiency of about 40%. The solar cell includes p-n junctions formed from indium gallium arsenide nitride (InGaAsN), gallium arsenide (GaAs) and indium gallium aluminum phosphide (InGaAlP) separated by n-p tunnel junctions. An optional germanium (Ge) p-n junction can be formed in the substrate upon which the other p-n junctions are grown. The bandgap energies for each p-n junction are tailored to provide substantially equal short-circuit currents for each p-n junction, thereby eliminating current bottlenecks and improving the overall energy conversion efficiency of the solar cell. Additionally, the use of an InGaAsN p-n junction overcomes super-bandgap energy losses that are present in conventional multi-junction solar cells. A method is also disclosed for fabricating the high-efficiency 3- or 4-junction solar cell by metal-organic chemical vapor deposition (MOCVD).

Targeting signal transduction in pancreatic cancer treatment.

PubMed

Yeh, Jen Jen; Der, Channing J

2007-05-01

Pancreatic cancer is a lethal disease with a 5-year survival rate of 4%. The only opportunity for improved survival continues to be complete surgical resection for those with localized disease. Although chemotherapeutic options are limited for the few patients with resectable disease, this problem is even more magnified in the majority (85%) of patients with unresectable or metastastic disease. Therefore, there is an urgent need for improved therapeutic options. The recent success of inhibitors of signal transduction for the treatment of other cancers supports the need to identify and validate aberrant signaling pathways important for pancreatic tumor growth. This review focuses on the validation of specific signaling networks and the present status of inhibitors of these pathways as therapeutic approaches for pancreatic cancer treatment.

Signal transduction pathways and transcription factors triggered by arsenic trioxide in leukemia cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sumi, Daigo, E-mail: sdaigo@ph.bunri-u.ac.j; Shinkai, Yasuhiro; Kumagai, Yoshito

2010-05-01

Arsenic trioxide (As{sub 2}O{sub 3}) is widely used to treat acute promyelocytic leukemia (APL). Several lines of evidence have indicated that As{sub 2}O{sub 3} affects signal transduction and transactivation of transcription factors, resulting in the stimulation of apoptosis in leukemia cells, because some transcription factors are reported to associate with the redox condition of the cells, and arsenicals cause oxidative stress. Thus, the disturbance and activation of the cellular signaling pathway and transcription factors due to reactive oxygen species (ROS) generation during arsenic exposure may explain the ability of As{sub 2}O{sub 3} to induce a complete remission in relapsed APLmore » patients. In this report, we review recent findings on ROS generation and alterations in signal transduction and in transactivation of transcription factors during As{sub 2}O{sub 3} exposure in leukemia cells.« less

[Effect of mitogen activated protein kinase signal transduction on apoptosis of PC12 cells induced by electromagnetic exposure].

PubMed

Yang, Xue-Sen; Zhang, Wei; Gong, Qian-Fen

2008-06-01

To observe the effect of mitogen activated protein kinase (MAPK) signal transduction system on the apoptosis induced by electromagnetic exposure in PC12 cells. After pretreated by SB203580 alone or together with U0126, PC12 cells were exposed to 65 mW/cm(2) electromagnetic wave for 20 min. The phosphorylations of ERK1/2, JNK and P38 MAPK were tested by Western-blot at 3 h and 24 h after electromagnetic exposure. The apoptosis of PC12 cells were detected by Annexin-V-FITC flow cytometry. U0126, but not SB203580 could inhibit the activation of ERK1/2 induced by electromagnetic exposure. U0126 and SB203580 had no effects on the activation of JNK. SB203580 could inhibit the activation of P38 MAPK significantly. But U0126 had no such effect on the activation of P38 MAPK. After pretreated by SB203580 alone or together with U0126, the apoptosis of PC12 cells decreased. But the pretreatment by U0126 alone had no influence on the apoptosis of PC12 cells. The P38 MAPK signal transduction modulate the apoptosis of PC12 cells induced by electromagnetic exposure. ERK signal transduction has no effect on the apoptosis of PC12 cells. JNK signal transduction may promote the apoptosis of PC12 cells in the early stage after electromagnetic exposure.

Phase I Trial of Adenovirus-Mediated IL-12 Gene Transduction in Patients with Recurrent Locally Advanced Prostate Cancer Following Therapy

DTIC Science & Technology

2005-10-01

salvage seed implant, cryotherapy ) or who have a rising PSA while on hormone therapy for locally advanced prostate cancer are as follows: a. A...Gene Transduction in Patients with Recurrent Locally Advanced Prostate Cancer Following Therapy PRINCIPAL INVESTIGATOR: Simon J. Hall, MD...CONTRACT NUMBER Phase I Trial of Adenovirus-Mediated IL-12 Gene Transduction in Patients with Recurrent Locally Advanced Prostate Cancer Following

Energy efficient engine high-pressure turbine supersonic cascade technology report

NASA Technical Reports Server (NTRS)

Kopper, F. C.; Milano, R.; Davis, R. L.; Dring, R. P.; Stoeffler, R. C.

1981-01-01

The performance of two vane endwall geometries and three blade sections for the high-pressure turbine was evaluated in terms of the efficiency requirements of the Energy Efficient Engine high-pressure turbine component. The van endwall designs featured a straight wall and S-wall configuration. The blade designs included a base blade, straightback blade, and overcambered blade. Test results indicated that the S-wall vane configuration and the base blade configuration offered the most promising performance characteristics for the Energy Efficient Engine high-pressure turbine component.

A functional TOC complex contributes to gravity signal transduction in Arabidopsis

PubMed Central

Strohm, Allison K.; Barrett-Wilt, Greg A.; Masson, Patrick H.

2014-01-01

Although plastid sedimentation has long been recognized as important for a plant's perception of gravity, it was recently shown that plastids play an additional function in gravitropism. The Translocon at the Outer envelope membrane of Chloroplasts (TOC) complex transports nuclear-encoded proteins into plastids, and a receptor of this complex, Toc132, was previously hypothesized to contribute to gravitropism either by directly functioning as a gravity signal transducer or by indirectly mediating the plastid localization of a gravity signal transducer. Here we show that mutations in multiple genes encoding TOC complex components affect gravitropism in a genetically sensitized background and that the cytoplasmic acidic domain of Toc132 is not required for its involvement in this process. Furthermore, mutations in TOC132 enhance the gravitropic defect of a mutant whose amyloplasts lack starch. Finally, we show that the levels of several nuclear-encoded root proteins are altered in toc132 mutants. These data suggest that the TOC complex indirectly mediates gravity signal transduction in Arabidopsis and support the idea that plastids are involved in gravitropism not only through their ability to sediment but also as part of the signal transduction mechanism. PMID:24795735

A functional TOC complex contributes to gravity signal transduction in Arabidopsis.

PubMed

Strohm, Allison K; Barrett-Wilt, Greg A; Masson, Patrick H

2014-01-01

Although plastid sedimentation has long been recognized as important for a plant's perception of gravity, it was recently shown that plastids play an additional function in gravitropism. The Translocon at the Outer envelope membrane of Chloroplasts (TOC) complex transports nuclear-encoded proteins into plastids, and a receptor of this complex, Toc132, was previously hypothesized to contribute to gravitropism either by directly functioning as a gravity signal transducer or by indirectly mediating the plastid localization of a gravity signal transducer. Here we show that mutations in multiple genes encoding TOC complex components affect gravitropism in a genetically sensitized background and that the cytoplasmic acidic domain of Toc132 is not required for its involvement in this process. Furthermore, mutations in TOC132 enhance the gravitropic defect of a mutant whose amyloplasts lack starch. Finally, we show that the levels of several nuclear-encoded root proteins are altered in toc132 mutants. These data suggest that the TOC complex indirectly mediates gravity signal transduction in Arabidopsis and support the idea that plastids are involved in gravitropism not only through their ability to sediment but also as part of the signal transduction mechanism.

Subsumed complexity: abiogenesis as a by-product of complex energy transduction

NASA Astrophysics Data System (ADS)

Adam, Z. R.; Zubarev, D.; Aono, M.; Cleaves, H. James

2017-11-01

The origins of life bring into stark relief the inadequacy of our current synthesis of thermodynamic, chemical, physical and information theory to predict the conditions under which complex, living states of organic matter can arise. Origins research has traditionally proceeded under an array of implicit or explicit guiding principles in lieu of a universal formalism for abiogenesis. Within the framework of a new guiding principle for prebiotic chemistry called subsumed complexity, organic compounds are viewed as by-products of energy transduction phenomena at different scales (subatomic, atomic, molecular and polymeric) that retain energy in the form of bonds that inhibit energy from reaching the ground state. There is evidence for an emergent level of complexity that is overlooked in most conceptualizations of abiogenesis that arises from populations of compounds formed from atomic energy input. We posit that different forms of energy input can exhibit different degrees of dissipation complexity within an identical chemical medium. By extension, the maximum capacity for organic chemical complexification across molecular and macromolecular scales subsumes, rather than emerges from, the underlying complexity of energy transduction processes that drive their production and modification. This article is part of the themed issue 'Reconceptualizing the origins of life'.

Energy efficient engine: High pressure turbine uncooled rig technology report

NASA Technical Reports Server (NTRS)

Gardner, W. B.

1979-01-01

Results obtained from testing five performance builds (three vane cascades and two rotating rigs of the Energy Efficient Engine uncooled rig have established the uncooled aerodynamic efficiency of the high-pressure turbine at 91.1 percent. This efficiency level was attained by increasing the rim speed and annulus area (AN(2)), and by increasing the turbine reaction level. The increase in AN(2) resulted in a performance improvement of 1.15 percent. At the design point pressure ratio, the increased reaction level rig demonstrated an efficiency of 91.1 percent. The results of this program have verified the aerodynamic design assumptions established for the Energy Efficient Engine high-pressure turbine component.

Endosomal protein traffic meets nuclear signal transduction head on.

PubMed

Horazdovsky, Bruce

2004-02-01

Rab5 plays a key role in controlling protein traffic through the early stages of the endocytic pathway. Previous studies on the modulators and effectors of Rab5 protein function have tied the regulation of several signal transduction pathways to the movement of protein through endocytic compartments. In the February 6, 2004, issue of Cell, Miaczynska et al. describe a surprising new link between Rab5 function and the nucleus by uncovering two new Rab5 effectors as potential regulators of the nucleosome remodeling and histone deacetylase protein complex NuRD/MeCP1.

808nm high-power high-efficiency GaAsP/GaInP laser bars

NASA Astrophysics Data System (ADS)

Wang, Ye; Yang, Ye; Qin, Li; Wang, Chao; Yao, Di; Liu, Yun; Wang, Lijun

2008-11-01

808nm high power diode lasers, which is rapidly maturing technology technically and commercially since the introduction in 1999 of complete kilowatt-scale diode laser systems, have important applications in the fields of industry and pumping solid-state lasers (DPSSL). High power and high power conversion efficiency are extremely important in diode lasers, and they could lead to new applications where space, weight and electrical power are critical. High efficiency devices generate less waste heat, which means less strain on the cooling system and more tolerance to thermal conductivity variation, a lower junction temperature and longer lifetimes. Diode lasers with Al-free materials have superior power conversion efficiency compared with conventional AlGaAs/GaAs devices because of their lower differential series resistance and higher thermal conductivity. 808nm GaAsP/GaInP broad-waveguide emitting diode laser bars with 1mm cavity length have been fabricated. The peak power can reach to 100.9W at 106.5A at quasicontinuous wave operation (200μs, 1000Hz). The maximum power conversion efficiency is 57.38%. Based on these high power laser bars, we fabricate a 1x3 arrays, the maximum power is 64.3W in continuous wave mode when the current is 25.0A. And the threshold current is 5.9A, the slope efficiency is 3.37 W/A.

Signal transduction by the Wnt family of ligands.

PubMed Central

Dale, T C

1998-01-01

The Wnt genes encode a large family of secreted polypeptides that mediate cell-cell communication in diverse developmental processes. The loss or inappropriate activation of Wnt expression has been shown to alter cell fate, morphogenesis and mitogenesis. Recent progress has identified Wnt receptors and components of an intracellular signalling pathway that mediate Wnt-dependent transcription. This review will highlight this 'core' Wnt signal-transduction pathway, but also aims to reveal the potential diversity of Wnt signalling targets. Particular attention will be paid to the overlap between developmental biology and oncogenesis, since recent progress shows Wnt signalling forms a paradigm for an interdisciplinary approach. PMID:9425102

Protein transduction: a novel tool for tissue regeneration.

PubMed

Cardoso, M Cristina; Leonhardt, Heinrich

2002-10-01

Tissue regeneration in humans is limited and excludes vitals organs like heart and brain. Transformation experiments with oncogenes like T antigen have shown that retrodifferentiation of the respective cells is possible but hard to control. To bypass the risk of cancer formation a protein therapy approach has been developed. The transient delivery of proteins rather than genes could still induce terminally-differentiated cells to reenter the cell cycle. This approach takes advantage of protein-transducing domains that mediate the transfer of cargo proteins into cells. The goal of this brief review is to outline the basics of protein transduction and to discuss potential applications for tissue regeneration.

High efficiency and broadband acoustic diodes

NASA Astrophysics Data System (ADS)

Fu, Congyi; Wang, Bohan; Zhao, Tianfei; Chen, C. Q.

2018-01-01

Energy transmission efficiency and working bandwidth are the two major factors limiting the application of current acoustic diodes (ADs). This letter presents a design of high efficiency and broadband acoustic diodes composed of a nonlinear frequency converter and a linear wave filter. The converter consists of two masses connected by a bilinear spring with asymmetric tension and compression stiffness. The wave filter is a linear mass-spring lattice (sonic crystal). Both numerical simulation and experiment show that the energy transmission efficiency of the acoustic diode can be improved by as much as two orders of magnitude, reaching about 61%. Moreover, the primary working band width of the AD is about two times of the cut-off frequency of the sonic crystal filter. The cut-off frequency dependent working band of the AD implies that the developed AD can be scaled up or down from macro-scale to micro- and nano-scale.

Experimental Realization of High-Efficiency Counterfactual Computation.

PubMed

Kong, Fei; Ju, Chenyong; Huang, Pu; Wang, Pengfei; Kong, Xi; Shi, Fazhan; Jiang, Liang; Du, Jiangfeng

2015-08-21

Counterfactual computation (CFC) exemplifies the fascinating quantum process by which the result of a computation may be learned without actually running the computer. In previous experimental studies, the counterfactual efficiency is limited to below 50%. Here we report an experimental realization of the generalized CFC protocol, in which the counterfactual efficiency can break the 50% limit and even approach unity in principle. The experiment is performed with the spins of a negatively charged nitrogen-vacancy color center in diamond. Taking advantage of the quantum Zeno effect, the computer can remain in the not-running subspace due to the frequent projection by the environment, while the computation result can be revealed by final detection. The counterfactual efficiency up to 85% has been demonstrated in our experiment, which opens the possibility of many exciting applications of CFC, such as high-efficiency quantum integration and imaging.

Experimental Realization of High-Efficiency Counterfactual Computation

NASA Astrophysics Data System (ADS)

Kong, Fei; Ju, Chenyong; Huang, Pu; Wang, Pengfei; Kong, Xi; Shi, Fazhan; Jiang, Liang; Du, Jiangfeng

2015-08-01

Counterfactual computation (CFC) exemplifies the fascinating quantum process by which the result of a computation may be learned without actually running the computer. In previous experimental studies, the counterfactual efficiency is limited to below 50%. Here we report an experimental realization of the generalized CFC protocol, in which the counterfactual efficiency can break the 50% limit and even approach unity in principle. The experiment is performed with the spins of a negatively charged nitrogen-vacancy color center in diamond. Taking advantage of the quantum Zeno effect, the computer can remain in the not-running subspace due to the frequent projection by the environment, while the computation result can be revealed by final detection. The counterfactual efficiency up to 85% has been demonstrated in our experiment, which opens the possibility of many exciting applications of CFC, such as high-efficiency quantum integration and imaging.

Detectable reporter gene expression following transduction of adenovirus and adeno-associated virus serotype 2 vectors within full-thickness osteoarthritic and unaffected canine cartilage in vitro and unaffected guinea pig cartilage in vivo.

PubMed

Santangelo, Kelly S; Baker, Sarah A; Nuovo, Gerard; Dyce, Jonathan; Bartlett, Jeffrey S; Bertone, Alicia L

2010-02-01

This study quantified and compared the transduction efficiencies of adenoviral (Ad), Arg-Gly-Asp (RGD)-modified Ad, adeno-associated viral serotype 2 (AAV2), and self-complementary AAV2 (scAAV2) vectors within full-thickness osteoarthritic (OA) and unaffected canine cartilage explants in vitro. Intraarticular administration of Ad and scAAV2 vectors was performed to determine the ability of these vectors to transduce unaffected guinea pig cartilage in vivo. Following explant exposure to vector treatment or control, the onset and surface distribution of reporter gene expression was monitored daily with fluorescent microscopy. At termination, explants were divided: one half was digested for analysis using flow cytometry; the remaining portion was used for histology and immunohistochemistry (IHC). Intact articular joints were collected for real-time RT-PCR and IHC to detect reporter gene expression following injection of selected vectors. Ad vector transduced focal areas along the perimeters of explants; the remaining vectors transduced chondrocytes across 100% of the surface. Greater mean transduction efficiencies were found with both AAV2 vectors as compared to the Ad vector (p < or = 0.026). Ad and Ad-RGD vectors transduced only superficial chondrocytes of OA and unaffected cartilage. Uniform reporter gene expression from AAV2 and scAAV2 was detected in the tangential and transitional zones of OA cartilage, but not deeper zones. AAV2 and scAAV2 vectors achieved partial and full-thickness transduction of unaffected cartilage. In vivo work revealed that scAAV2 vector, but not Ad vector, transduced deeper zones of cartilage and menisci. This study demonstrates that AAV2 and scAAV2 are reliable vectors for use in cartilage in vitro and in vivo. (c) 2009 Orthopaedic Research Society.

Realization of highly efficient hexagonal boron nitride neutron detectors

DOE PAGES

Maity, A.; Doan, T. C.; Li, J.; ...

2016-08-16

Here, we report the achievement of highly efficient 10B enriched hexagonal boron nitride (h- 10BN) direct conversion neutron detectors. These detectors were realized from freestanding 4-in. diameter h- 10BN wafers 43 μm in thickness obtained from epitaxy growth and subsequent mechanical separation from sapphire substrates. Both sides of the film were subjected to ohmic contact deposition to form a simple vertical “photoconductor-type” detector. Transport measurements revealed excellent vertical transport properties including high electrical resistivity (>10 13 Ω cm) and mobility-lifetime (μτ) products. A much larger μτ product for holes compared to that of electrons along the c-axis of h- BNmore » was observed, implying that holes (electrons) behave like majority (minority) carriers in undoped h- BN. Exposure to thermal neutrons from a californium-252 ( 252Cf) source moderated by a high density polyethylene moderator reveals that 43 μm h- 10BN detectors possess 51.4% detection efficiency at a bias voltage of 400 V, which is the highest reported efficiency for any semiconductor-based neutron detector. The results point to the possibility of obtaining highly efficient, compact solid-state neutron detectors with high gamma rejection and low manufacturing and maintenance costs.« less

Identification of second messenger mediating signal transduction in the olfactory receptor cell.

PubMed

Takeuchi, Hiroko; Kurahashi, Takashi

2003-11-01

One of the biggest controversial issues in the research of olfaction has been the mechanism underlying response generation to odorants that have been shown to fail to produce cAMP when tested by biochemical assays with olfactory ciliary preparations. Such observations are actually the original source proposing a possibility for the presence of multiple and parallel transduction pathways. In this study the activity of transduction channels in the olfactory cilia was recorded in cells that retained their abilities of responding to odorants that have been reported to produce InsP3 (instead of producing cAMP, and therefore tentatively termed "InsP3 odorants"). At the same time, the cytoplasmic cNMP concentration ([cNMP]i) was manipulated through the photolysis of caged compounds to examine their real-time interactions with odorant responses. Properties of responses induced by both InsP3 odorants and cytoplasmic cNMP resembled each other in their unique characteristics. Reversal potentials of currents were 2 mV for InsP3 odorant responses and 3 mV for responses induced by cNMP. Current and voltage (I-V) relations showed slight outward rectification. Both responses showed voltage-dependent adaptation when examined with double pulse protocols. When brief pulses of the InsP3 odorant and cytoplasmic cNMP were applied alternatively, responses expressed cross-adaptation with each other. Furthermore, both responses were additive in a manner as predicted quantitatively by the theory that signal transduction is mediated by the increase in cytoplasmic cAMP. With InsP3 odorants, actually, remarkable responses could be detected in a small fraction of cells ( approximately 2%), explaining the observation for a small production of cAMP in ciliary preparations obtained from the entire epithelium. The data will provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants.

High efficiency crystalline silicon solar cells

NASA Technical Reports Server (NTRS)

Sah, C. Tang

1986-01-01

A review of the entire research program since its inception ten years ago is given. The initial effort focused on the effects of impurities on the efficiency of silicon solar cells to provide figures of maximum allowable impurity density for efficiencies up to about 16 to 17%. Highly accurate experimental techniques were extended to characterize the recombination properties of the residual imputities in the silicon solar cell. A numerical simulator of the solar cell was also developed, using the Circuit Technique for Semiconductor Analysis. Recent effort focused on the delineation of the material and device parameters which limited the silicon efficiency to below 20% and on an investigation of cell designs to break the 20% barrier. Designs of the cell device structure and geometry can further reduce recombination losses as well as the sensitivity and criticalness of the fabrication technology required to exceed 20%. Further research is needed on the fundamental characterization of the carrier recombination properties at the chemical impurity and physical defect centers. It is shown that only single crystalline silicon cell technology can be successful in attaining efficiencies greater than 20%.

Production technology for high efficiency ion implanted solar cells

NASA Technical Reports Server (NTRS)

Kirkpatrick, A. R.; Minnucci, J. A.; Greenwald, A. C.; Josephs, R. H.

1978-01-01

Ion implantation is being developed for high volume automated production of silicon solar cells. An implanter designed for solar cell processing and able to properly implant up to 300 4-inch wafers per hour is now operational. A machine to implant 180 sq m/hr of solar cell material has been designed. Implanted silicon solar cells with efficiencies exceeding 16% AM1 are now being produced and higher efficiencies are expected. Ion implantation and transient processing by pulsed electron beams are being integrated with electrostatic bonding to accomplish a simple method for large scale, low cost production of high efficiency solar cell arrays.

Design method of high-efficient 
LED headlamp lens.

PubMed

Chen, Fei; Wang, Kai; Qin, Zong; Wu, Dan; Luo, Xiaobing; Liu, Sheng

2010-09-27

Low optical efficiency of light-emitting diode (LED) based headlamp is one of the most important issues to obstruct applications of LEDs in headlamp. An effective high-efficient LED headlamp freeform lens design method is introduced in this paper. A low-beam lens and a high-beam lens for LED headlamp are designed according to this method. Monte Carlo ray tracing simulation results demonstrate that the LED headlamp with these two lenses can fully comply with the ECE regulation without any other lens or reflector. Moreover, optical efficiencies of both these two lenses are more than 88% in theory.

High efficiency silicon solar cell based on asymmetric nanowire.

PubMed

Ko, Myung-Dong; Rim, Taiuk; Kim, Kihyun; Meyyappan, M; Baek, Chang-Ki

2015-07-08

Improving the efficiency of solar cells through novel materials and devices is critical to realize the full potential of solar energy to meet the growing worldwide energy demands. We present here a highly efficient radial p-n junction silicon solar cell using an asymmetric nanowire structure with a shorter bottom core diameter than at the top. A maximum short circuit current density of 27.5 mA/cm(2) and an efficiency of 7.53% were realized without anti-reflection coating. Changing the silicon nanowire (SiNW) structure from conventional symmetric to asymmetric nature improves the efficiency due to increased short circuit current density. From numerical simulation and measurement of the optical characteristics, the total reflection on the sidewalls is seen to increase the light trapping path and charge carrier generation in the radial junction of the asymmetric SiNW, yielding high external quantum efficiency and short circuit current density. The proposed asymmetric structure has great potential to effectively improve the efficiency of the SiNW solar cells.

High Performance Computing Meets Energy Efficiency - Continuum Magazine |

Science.gov Websites

NREL High Performance Computing Meets Energy Efficiency High Performance Computing Meets Energy turbines. Simulation by Patrick J. Moriarty and Matthew J. Churchfield, NREL The new High Performance Computing Data Center at the National Renewable Energy Laboratory (NREL) hosts high-speed, high-volume data

Development of high-efficiency solar cells on silicon web

NASA Technical Reports Server (NTRS)

Rohatgi, A.; Meier, D. L.; Campbell, R. B.; Seidensticker, R. G.; Rai-Choudhury, P.

1985-01-01

High-efficiency dendritic cells were discussed. The influence of twin planes and heat treatment on the location and effect of trace impurities was of particular interest. Proper heat treatment often increases efficiency by causing impurities to pile up at twin planes. Oxide passivation had a beneficial effect on efficiency. A very efficient antireflective (AR) coating of zinc selenide and magnesium fluoride was designed and fabricated. An aluminum back-surface reflector was also effective.

High-Efficiency Hall Thruster Discharge Power Converter

NASA Technical Reports Server (NTRS)

Jaquish, Thomas

2015-01-01

Busek Company, Inc., is designing, building, and testing a new printed circuit board converter. The new converter consists of two series or parallel boards (slices) intended to power a high-voltage Hall accelerator (HiVHAC) thruster or other similarly sized electric propulsion devices. The converter accepts 80- to 160-V input and generates 200- to 700-V isolated output while delivering continually adjustable 300-W to 3.5-kW power. Busek built and demonstrated one board that achieved nearly 94 percent efficiency the first time it was turned on, with projected efficiency exceeding 97 percent following timing software optimization. The board has a projected specific mass of 1.2 kg/kW, achieved through high-frequency switching. In Phase II, Busek optimized to exceed 97 percent efficiency and built a second prototype in a form factor more appropriate for flight. This converter then was integrated with a set of upgraded existing boards for powering magnets and the cathode. The program culminated with integrating the entire power processing unit and testing it on a Busek thruster and on NASA's HiVHAC thruster.

High-efficiency 20 GHz traveling wave tube development for space communications

NASA Technical Reports Server (NTRS)

Aldana, S. L.; Tamashiro, R. N.

1991-01-01

A 75 watt CW high efficiency helix TWT operating at 20 GHz was developed for satellite communication systems. The purpose was to extend the performance capabilities of helix TWTs by using recent technology developments. The TWT described is a unique design because high overall efficiency is obtained with a low perveance beam. In the past, low perveance designs resulted in low beam efficiencies. However, due to recent breakthoughs in diamond rod technology and in collector electrode materials, high efficiencies can now be achieved with low perveance beams. The advantage of a low perveance beam is a reduction in space charge within the beam which translates to more efficient collector operation. In addition, this design incorporates textured graphite electrodes which further enhance collector operation by suppressing backstreaming secondaries. The diamond supported helix circuit features low RF losses, high interaction impedance, good thermal handling capability and has been designed to compensate for the low perveance beam. One more discussed tube feature is the use of a velocity taper in the output helix that achieves low signal distortion while maintaining high efficiency.

Loss mechanisms in high-efficiency solar cells: Study of material properties and high-efficiency solar-cell performance on material composition: Project tasks

NASA Technical Reports Server (NTRS)

Sah, C. T.

1985-01-01

Loss mechanisms in high-efficiency solar cells were discussed. Fundamental limitations and practical solutions were stressed. Present cell efficiency is limited by many recombination sites: emitter, base, contacts, and oxide/silicon interface. Use of polysilicon passivation was suggested. After reduction of these losses, a 25% efficient cell could be built. A floating emitter cell design was shown that had the potential of low recombination losses.

Traceless Bioresponsive Shielding of Adenovirus Hexon with HPMA Copolymers Maintains Transduction Capacity In Vitro and In Vivo

PubMed Central

Prill, Jan-Michael; Šubr, Vladimír; Pasquarelli, Noemi; Engler, Tatjana; Hoffmeister, Andrea; Kochanek, Stefan; Ulbrich, Karel; Kreppel, Florian

2014-01-01

Capsid surface shielding of adenovirus vectors with synthetic polymers is an emerging technology to reduce unwanted interactions of the vector particles with cellular and non-cellular host components. While it has been shown that attachment of shielding polymers allows prevention of undesired interactions, it has become evident that a shield which is covalently attached to the vector surface can negatively affect gene transfer efficiency. Reasons are not only a limited receptor-binding ability of the shielded vectors but also a disturbance of intracellular trafficking processes, the latter depending on the interaction of the vector surface with the cellular transport machinery. A solution might be the development of bioresponsive shields that are stably maintained outside the host cell but released upon cell entry to allow for efficient gene delivery to the nucleus. Here we provide a systematic comparison of irreversible versus bioresponsive shields based on synthetic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers. In addition, the chemical strategy used for generation of the shield allowed for a traceless bioresponsive shielding, i.e., polymers could be released from the vector particles without leaving residual linker residues. Our data demonstrated that only a bioresponsive shield maintained the high gene transfer efficiency of adenovirus vectors both in vitro and in vivo. As an example for bioresponsive HPMA copolymer release, we analyzed the in vivo gene transfer in the liver. We demonstrated that both the copolymer's charge and the mode of shielding (irreversible versus traceless bioresponsive) profoundly affected liver gene transfer and that traceless bioresponsive shielding with positively charged HPMA copolymers mediated FX independent transduction of hepatocytes. In addition, we demonstrated that shielding with HPMA copolymers can mediate a prolonged blood circulation of vector particles in mice. Our results have significant implications for the

On-chip optical transduction scheme for graphene nano-electro-mechanical systems in silicon-photonic platform.

PubMed

Dash, Aneesh; Selvaraja, S K; Naik, A K

2018-02-15

We present a scheme for on-chip optical transduction of strain and displacement of graphene-based nano-electro-mechanical systems (NEMS). A detailed numerical study on the feasibility of three silicon-photonic integrated circuit configurations is presented: the Mach-Zehnder interferometer (MZI), the micro-ring resonator, and the ring-loaded MZI. An index sensing based technique using an MZI loaded with a ring resonator with a moderate Q-factor of 2400 can yield a sensitivity of 28  fm/Hz and 6.5×10 -6 %/Hz for displacement and strain, respectively. Though any phase-sensitive integrated-photonic device could be used for optical transduction, here we show that optimal sensitivity is achievable by combining resonance with phase sensitivity.

High-resolution high-efficiency multilayer Fresnel zone plates for soft and hard x-rays

NASA Astrophysics Data System (ADS)

Sanli, Umut T.; Keskinbora, Kahraman; Gregorczyk, Keith; Leister, Jonas; Teeny, Nicolas; Grévent, Corinne; Knez, Mato; Schütz, Gisela

2015-09-01

X-ray microscopy enables high spatial resolutions, high penetration depths and characterization of a broad range of materials. Calculations show that nanometer range resolution is achievable in the hard X-ray regime by using Fresnel zone plates (FZPs) if certain conditions are satisfied. However, this requires, among other things, aspect ratios of several thousands. The multilayer (ML) type FZPs, having virtually unlimited aspect ratios, are strong candidates to achieve single nanometer resolutions. Our research is focused on the fabrication of ML-FZPs which encompasses deposition of multilayers over a glass fiber via the atomic layer deposition (ALD), which is subsequently sliced in the optimum thickness for the X-ray energy by a focused ion beam (FIB). We recently achieved aberration free imaging by resolving 21 nm features with an efficiency of up to 12.5 %, the highest imaging resolution achieved by an ML-FZP. We also showed efficient focusing of 7.9 keV X-rays down to 30 nm focal spot size (FWHM). For resolutions below ~10 nm, efficiencies would decrease significantly due to wave coupling effects. To compensate this effect high efficiency, low stress materials have to be researched, as lower intrinsic stresses will allow fabrication of larger FZPs with higher number of zones, leading to high light intensity at the focus. As a first step we fabricated an ML-FZP with a diameter of 62 μm, an outermost zone width of 12 nm and 452 active zones. Further strategies for fabrication of high resolution high efficiency multilayer FZPs will also be discussed.

High Quantum Efficiency OLED Lighting Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiang, Joseph

The overall goal of the program was to apply improvements in light outcoupling technology to a practical large area plastic luminaire, and thus enable the product vision of an extremely thin form factor high efficiency large area light source. The target substrate was plastic and the baseline device was operating at 35 LPW at the start of the program. The target LPW of the program was a >2x improvement in the LPW efficacy and the overall amount of light to be delivered was relatively high 900 lumens. Despite the extremely difficult challenges associated with scaling up a wet solution processmore » on plastic substrates, the program was able to make substantial progress. A small molecule wet solution process was successfully implemented on plastic substrates with almost no loss in efficiency in transitioning from the laboratory scale glass to large area plastic substrates. By transitioning to a small molecule based process, the LPW entitlement increased from 35 LPW to 60 LPW. A further 10% improvement in outcoupling efficiency was demonstrated via the use of a highly reflecting cathode, which reduced absorptive loss in the OLED device. The calculated potential improvement in some cases is even larger, ~30%, and thus there is considerable room for optimism in improving the net light coupling efficacy, provided absorptive loss mechanisms are eliminated. Further improvements are possible if scattering schemes such as the silver nanowire based hard coat structure are fully developed. The wet coating processes were successfully scaled to large area plastic substrate and resulted in the construction of a 900 lumens luminaire device.« less

High-efficiency GaAs concentrator space cells

NASA Technical Reports Server (NTRS)

Werthen, J. G.; Virshup, G. F.; Macmillan, H. F.; Ford, C. W.; Hamaker, H. C.

1987-01-01

High efficiency Al sub x Ga sub 1-x As/GaAs heteroface solar concentrator cells have been developed for space applications. The cells, which were grown using metalorganic chemical vapor deposition (MOCVD), have been fabricated in both the p-n and n-p configurations. Magnesium and zinc are used as the p-type dopants, and Se is used as the n-type dopant. The space cells, which are designed for use in a Cassegrainian concentrator operating at 100 suns, AMO, have a circular illuminated area 4 mm in diameter on a 5 mm by 5 mm cell. These cells have exhibited flash-tested efficiencies as high as 23.6 percent at 28 C and 21.6 percent at 80 C.

Development of high-efficiency solar cells on silicon web

NASA Technical Reports Server (NTRS)

Meier, D. L.; Greggi, J.; Okeeffe, T. W.; Rai-Choudhury, P.

1986-01-01

Work was performed to improve web base material with a goal of obtaining solar cell efficiencies in excess of 18% (AM1). Efforts in this program are directed toward identifying carrier loss mechanisms in web silicon, eliminating or reducing these mechanisms, designing a high efficiency cell structure with the aid of numerical models, and fabricating high efficiency web solar cells. Fabrication techniques must preserve or enhance carrier lifetime in the bulk of the cell and minimize recombination of carriers at the external surfaces. Three completed cells were viewed by cross-sectional transmission electron microscopy (TEM) in order to investigate further the relation between structural defects and electrical performance of web cells. Consistent with past TEM examinations, the cell with the highest efficiency (15.0%) had no dislocations but did have 11 twin planes.

High-efficiency solar cell and method for fabrication

DOEpatents

Hou, H.Q.; Reinhardt, K.C.

1999-08-31

A high-efficiency 3- or 4-junction solar cell is disclosed with a theoretical AM0 energy conversion efficiency of about 40%. The solar cell includes p-n junctions formed from indium gallium arsenide nitride (InGaAsN), gallium arsenide (GaAs) and indium gallium aluminum phosphide (InGaAlP) separated by n-p tunnel junctions. An optional germanium (Ge) p-n junction can be formed in the substrate upon which the other p-n junctions are grown. The bandgap energies for each p-n junction are tailored to provide substantially equal short-circuit currents for each p-n junction, thereby eliminating current bottlenecks and improving the overall energy conversion efficiency of the solar cell. Additionally, the use of an InGaAsN p-n junction overcomes super-bandgap energy losses that are present in conventional multi-junction solar cells. A method is also disclosed for fabricating the high-efficiency 3- or 4-junction solar cell by metal-organic chemical vapor deposition (MOCVD). 4 figs.

High extraction efficiency ultraviolet light-emitting diode

DOEpatents

Wierer, Jonathan; Montano, Ines; Allerman, Andrew A.

2015-11-24

Ultraviolet light-emitting diodes with tailored AlGaN quantum wells can achieve high extraction efficiency. For efficient bottom light extraction, parallel polarized light is preferred, because it propagates predominately perpendicular to the QW plane and into the typical and more efficient light escape cones. This is favored over perpendicular polarized light that propagates along the QW plane which requires multiple, lossy bounces before extraction. The thickness and carrier density of AlGaN QW layers have a strong influence on the valence subband structure, and the resulting optical polarization and light extraction of ultraviolet light-emitting diodes. At Al>0.3, thinner QW layers (<2.5 nm are preferred) result in light preferentially polarized parallel to the QW plane. Also, active regions consisting of six or more QWs, to reduce carrier density, and with thin barriers, to efficiently inject carriers in all the QWs, are preferred.

Single residue AAV capsid mutation improves transduction of photoreceptors in the Abca4-/- mouse and bipolar cells in the rd1 mouse and human retina ex vivo.

PubMed

De Silva, Samantha R; Charbel Issa, Peter; Singh, Mandeep S; Lipinski, Daniel M; Barnea-Cramer, Alona O; Walker, Nathan J; Barnard, Alun R; Hankins, Mark W; MacLaren, Robert E

2016-11-01

Gene therapy using adeno-associated viral (AAV) vectors for the treatment of retinal degenerations has shown safety and efficacy in clinical trials. However, very high levels of vector expression may be necessary for the treatment of conditions such as Stargardt disease where a dual vector approach is potentially needed, or in optogenetic strategies for end-stage degeneration in order to achieve maximal light sensitivity. In this study, we assessed two vectors with single capsid mutations, rAAV2/2(Y444F) and rAAV2/8(Y733F) in their ability to transduce retina in the Abca4 -/- and rd1 mouse models of retinal degeneration. We noted significantly increased photoreceptor transduction using rAAV2/8(Y733F) in the Abca4 -/- mouse, in contrast to previous work where vectors tested in this model have shown low levels of photoreceptor transduction. Bipolar cell transduction was achieved following subretinal delivery of both vectors in the rd1 mouse, and via intravitreal delivery of rAAV2/2(Y444F). The successful use of rAAV2/8(Y733F) to target bipolar cells was further validated on human tissue using an ex vivo culture system of retinal explants. Capsid mutant AAV vectors transduce human retinal cells and may be particularly suited to treat retinal degenerations in which high levels of transgene expression are required.

Modern energy efficient technologies of high-rise construction

NASA Astrophysics Data System (ADS)

Lukmanova, Inessa; Golov, Roman

2018-03-01

The paper analyzes modern energy-efficient technologies, both being applied, and only introduced into the application in the construction of high-rise residential buildings. All technologies are systematized by the authors as part of a unified model of "Arrows of Energy-Efficient Technologies", which imply performing energy-saving measures in the design, construction and operation of buildings.

High Efficiency Solar Integrated Roof Membrane Product

DOE Office of Scientific and Technical Information (OSTI.GOV)

Partyka, Eric; Shenoy, Anil

2013-05-15

This project was designed to address the Solar Energy Technology Program objective, to develop new methods to integrate photovoltaic (PV) cells or modules within a building-integrated photovoltaic (BIPV) application that will result in lower installed cost as well as higher efficiencies of the encapsulated/embedded PV module. The technology assessment and development focused on the evaluation and identification of manufacturing technologies and equipment capable of producing such low-cost, high-efficiency, flexible BIPV solar cells on single-ply roofing membranes.

High bandgap III-V alloys for high efficiency optoelectronics

DOEpatents

Alberi, Kirstin; Mascarenhas, Angelo; Wanlass, Mark

2017-01-10

High bandgap alloys for high efficiency optoelectronics are disclosed. An exemplary optoelectronic device may include a substrate, at least one Al.sub.1-xIn.sub.xP layer, and a step-grade buffer between the substrate and at least one Al.sub.1-xIn.sub.xP layer. The buffer may begin with a layer that is substantially lattice matched to GaAs, and may then incrementally increase the lattice constant in each sequential layer until a predetermined lattice constant of Al.sub.1-xIn.sub.xP is reached.

Sel1-like repeat proteins in signal transduction.

PubMed

Mittl, Peer R E; Schneider-Brachert, Wulf

2007-01-01

Solenoid proteins, which are distinguished from general globular proteins by their modular architectures, are frequently involved in signal transduction pathways. Proteins from the tetratricopeptide repeat (TPR) and Sel1-like repeat (SLR) families share similar alpha-helical conformations but different consensus sequence lengths and superhelical topologies. Both families are characterized by low sequence similarity levels, rendering the identification of functional homologous difficult. Therefore current knowledge of the molecular and cellular functions of the SLR proteins Sel1, Hrd3, Chs4, Nif1, PodJ, ExoR, AlgK, HcpA, Hsp12, EnhC, LpnE, MotX, and MerG has been reviewed. Although SLR proteins possess different cellular functions they all seem to serve as adaptor proteins for the assembly of macromolecular complexes. Sel1, Hrd3, Hsp12 and LpnE are activated under cellular stress. The eukaryotic Sel1 and Hrd3 proteins are involved in the ER-associated protein degradation, whereas the bacterial LpnE, EnhC, HcpA, ExoR, and AlgK proteins mediate the interactions between bacterial and eukaryotic host cells. LpnE and EnhC are responsible for the entry of L. pneumophila into epithelial cells and macrophages. ExoR from the symbiotic microorganism S. melioti and AlgK from the pathogen P. aeruginosa regulate exopolysaccaride synthesis. Nif1 and Chs4 from yeast are responsible for the regulation of mitosis and septum formation during cell division, respectively, and PodJ guides the cellular differentiation during the cell cycle of the bacterium C. crescentus. Taken together the SLR motif establishes a link between signal transduction pathways from eukaryotes and bacteria. The SLR motif is so far absent from archaea. Therefore the SLR could have developed in the last common ancestor between eukaryotes and bacteria.

High-efficiency machining methods for aviation materials

NASA Astrophysics Data System (ADS)

Kononov, V. K.

1991-07-01

The papers contained in this volume present results of theoretical and experimental studies aimed at increasing the efficiency of cutting tools during the machining of high-temperature materials and titanium alloys. Specific topics discussed include a study of the performance of disk cutters during the machining of flexible parts of a high-temperature alloy, VZhL14N; a study of the wear resistance of cutters of hard alloys of various types; effect of a deformed electric field on the precision of the electrochemical machining of gas turbine engine components; and efficient machining of parts of composite materials. The discussion also covers the effect of the technological process structure on the residual stress distribution in the blades of gas turbine engines; modeling of the multiparameter assembly of engineering products for a specified priority of geometrical output parameters; and a study of the quality of the surface and surface layer of specimens machined by a high-temperature pulsed plasma.

High-efficiency silicon solar-cell design and practical barriers

NASA Technical Reports Server (NTRS)

Mokashi, A.

1985-01-01

A numerical evaluation technique is used to study the impact of practical barriers, such as heavy doping effects (Auger recombination, band gap narrowing), surface recombination, shadowing losses and minority-carrier lifetime (Tau), on a high efficiency silicon solar cell performance. Considering a high Tau of 1 ms, efficiency of a silicon solar cell of the hypothetical case is estimated to be around 29%. This is comparable with (detailed balance limit) maximum efficiency of a p-n junction solar cell of 30%. Value of Tau is varied from 1 second to 20 micro. Heavy doping effects, and realizable values of surface recombination velocities and shadowing, are then considered in succession and their influence on cell efficiency is evaluated and quantified. These practical barriers cause the cell efficiency to reduce from the maximum value of 29% to the experimentally achieved value of about 19%. Improvement in open circuit voltage V sub oc is required to achieve cell efficiency greater than 20%. Increased value of Tau reduces reverse saturation current and, hence, improves V sub oc. Control of surface recombination losses becomes critical at higher V sub oc. Substantial improvement in Tau and considerable reduction in surface recombination velocities is essential to achieve cell efficiencies greater than 20%.

Highly Flexible and Efficient Solar Steam Generation Device.

PubMed

Chen, Chaoji; Li, Yiju; Song, Jianwei; Yang, Zhi; Kuang, Yudi; Hitz, Emily; Jia, Chao; Gong, Amy; Jiang, Feng; Zhu, J Y; Yang, Bao; Xie, Jia; Hu, Liangbing

2017-08-01

Solar steam generation with subsequent steam recondensation has been regarded as one of the most promising techniques to utilize the abundant solar energy and sea water or other unpurified water through water purification, desalination, and distillation. Although tremendous efforts have been dedicated to developing high-efficiency solar steam generation devices, challenges remain in terms of the relatively low efficiency, complicated fabrications, high cost, and inability to scale up. Here, inspired by the water transpiration behavior of trees, the use of carbon nanotube (CNT)-modified flexible wood membrane (F-Wood/CNTs) is demonstrated as a flexible, portable, recyclable, and efficient solar steam generation device for low-cost and scalable solar steam generation applications. Benefitting from the unique structural merits of the F-Wood/CNTs membrane-a black CNT-coated hair-like surface with excellent light absorbability, wood matrix with low thermal conductivity, hierarchical micro- and nanochannels for water pumping and escaping, solar steam generation device based on the F-Wood/CNTs membrane demonstrates a high efficiency of 81% at 10 kW cm -2 , representing one of the highest values ever-reported. The nature-inspired design concept in this study is straightforward and easily scalable, representing one of the most promising solutions for renewable and portable solar energy generation and other related phase-change applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Energy transduction inside vesicles, photocatalysis by titanium dioxide and formation of NADH

NASA Astrophysics Data System (ADS)

Summers, David; Noveron, Juan; Rodoni, David; Basa, Ranor

A number of theories on the origin and early evolution of life have focused on the role of lipid bilayer membrane structures (vesicles). These vesicles are similar to modern cellular membranes , and have been postulated to have been abiotically formed and spontaneously assemble on the prebiotic Earth to provide compartments for early cellular life. They can contain water-soluble species, concentrate species, and have the potential to catalyze reactions. The origin of the use of photochemical energy to drive metabolism (ie. energy transduction) is also one of the central issues in our attempts to understand the origin and evolution of life. When did energy transduction and photosynthesis begin? What was the original system for capturing photochemical energy? How simple can such a system be? It has been postulated that vesicle structures developed the ability to capture and transduce light, providing energy for reactions. It has been shown that pH gradients can be photo-chemically created, but it has been found difficult to couple these to drive chemical reactions. Minerals can introduce a number of properties to a vesicle system. The incorporation of clay particles into vesicles can provide catalytic activity that mediates both vesicle assembly and RNA oligomerization. It is known that colloidal semiconducting mineral particles can act as photocatalysts and drive redox chemistry. We show that encapsulation of these particles has the potential to provide a source of energy transduction inside vesicles, and thereby drive protocellular chemistry and represent a model system for early photosynthesis. TiO2 particles can be incorporated into vesicles and retain their photoactivity through the dehydration/rehydration cycles that have been shown to be able concentrate species inside a vesicle. It is shown that these can be used to produce biochemical species such as enzymatically active NADH in such structures. This system demonstrates a simple energy source inside vesicles

Mechano-electrical transduction currents in isolated vestibular hair cells of the chick.

PubMed

Ohmori, H

1985-02-01

Properties of a mechano-electrical transduction channel were studied in enzymatically dissociated chick vestibular hair cells by using a whole-cell recording variation of the patch voltage-clamp technique. The apical hair bundle was stimulated by a glass rod which moved along a one-dimensional axis when stimulated by either a triangular or a trapezoidal command voltage. The motion of the glass rod was monitored optically using a photodiode. In response to triangular stimuli, the hair cell generated a current of triangular wave form with occasional step-like spiky or zigzag-appearing events. Control experiments confirmed that the current was generated only when the hair bundle was displaced towards the tallest stereocilium. The mechano-sensitive current was blocked by streptomycin and by neomycin. The blockage by streptomycin was clearly voltage dependent: the reduction of the current became larger with hyperpolarization of the membrane. This suggests that the positively charged antibiotic molecules plug the mechanically gated channels. From the evidence presented in 3 and 4 above, the mechano-sensitive current recorded here was identified as the mechano-electrical transduction (m-e.t.) current. The permeability of the m-e.t. channel to various monovalent cations was determined from reversal potential measurements. Since a CsCl-EGTA intracellular medium was used, all the permeabilities were calculated relative to PCs. The sequence of permeabilities was Li greater than Na greater than or equal to K greater than or equal to Rb greater than Cs greater than choline greater than TMA greater than TEA. External Ca ions were indispensable for the recording of transduction current and Sr ions could replace Ca ions without loss of the transduction activity. The minimum [Ca]o for stable generation of the m-e.t. current was 20 microM in Cs saline. The addition of 50-200 microM-Ca to the isotonic Ba saline could maintain the m-e.t. current. The m-e.t. current was observed in

Progestins alter photo-transduction cascade and circadian rhythm network in eyes of zebrafish (Danio rerio)

NASA Astrophysics Data System (ADS)

Zhao, Yanbin; Fent, Karl

2016-02-01

Environmental progestins are implicated in endocrine disruption in vertebrates. Additional targets that may be affected in organisms are poorly known. Here we report that progesterone (P4) and drospirenone (DRS) interfere with the photo-transduction cascade and circadian rhythm network in the eyes of zebrafish. Breeding pairs of adult zebrafish were exposed to P4 and DRS for 21 days with different measured concentrations of 7-742 ng/L and 99-13´650 ng/L, respectively. Of totally 10 key photo-transduction cascade genes analyzed, transcriptional levels of most were significantly up-regulated, or normal down-regulation was attenuated. Similarly, for some circadian rhythm genes, dose-dependent transcriptional alterations were also observed in the totally 33 genes analyzed. Significant alterations occurred even at environmental relevant levels of 7 ng/L P4. Different patterns were observed for these transcriptional alterations, of which, the nfil3 family displayed most significant changes. Furthermore, we demonstrate the importance of sampling time for the determination and interpretation of gene expression data, and put forward recommendations for sampling strategies to avoid false interpretations. Our results suggest that photo-transduction signals and circadian rhythm are potential targets for progestins. Further studies are required to assess alterations on the protein level, on physiology and behavior, as well as on implications in mammals.

High Efficiency Heat Exchanger for High Temperature and High Pressure Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sienicki, James J.; Lv, Qiuping; Moisseytsev, Anton

CompRex, LLC (CompRex) specializes in the design and manufacture of compact heat exchangers and heat exchange reactors for high temperature and high pressure applications. CompRex’s proprietary compact technology not only increases heat exchange efficiency by at least 25 % but also reduces footprint by at least a factor of ten compared to traditional shell-and-tube solutions of the same capacity and by 15 to 20 % compared to other currently available Printed Circuit Heat Exchanger (PCHE) solutions. As a result, CompRex’s solution is especially suitable for Brayton cycle supercritical carbon dioxide (sCO2) systems given its high efficiency and significantly lower capitalmore » and operating expenses. CompRex has already successfully demonstrated its technology and ability to deliver with a pilot-scale compact heat exchanger that was under contract by the Naval Nuclear Laboratory for sCO2 power cycle development. The performance tested unit met or exceeded the thermal and hydraulic specifications with measured heat transfer between 95 to 98 % of maximum heat transfer and temperature and pressure drop values all consistent with the modeled values. CompRex’s vision is to commercialize its compact technology and become the leading provider for compact heat exchangers and heat exchange reactors for various applications including Brayton cycle sCO2 systems. One of the limitations of the sCO2 Brayton power cycle is the design and manufacturing of efficient heat exchangers at extreme operating conditions. Current diffusion-bonded heat exchangers have limitations on the channel size through which the fluid travels, resulting in excessive solid material per heat exchanger volume. CompRex’s design allows for more open area and shorter fluid proximity for increased heat transfer efficiency while sustaining the structural integrity needed for the application. CompRex is developing a novel improvement to its current heat exchanger design where fluids are directed to

A pulse-compression-ring circuit for high-efficiency electric propulsion.

PubMed

Owens, Thomas L

2008-03-01

A highly efficient, highly reliable pulsed-power system has been developed for use in high power, repetitively pulsed inductive plasma thrusters. The pulsed inductive thruster ejects plasma propellant at a high velocity using a Lorentz force developed through inductive coupling to the plasma. Having greatly increased propellant-utilization efficiency compared to chemical rockets, this type of electric propulsion system may one day propel spacecraft on long-duration deep-space missions. High system reliability and electrical efficiency are extremely important for these extended missions. In the prototype pulsed-power system described here, exceptional reliability is achieved using a pulse-compression circuit driven by both active solid-state switching and passive magnetic switching. High efficiency is achieved using a novel ring architecture that recovers unused energy in a pulse-compression system with minimal circuit loss after each impulse. As an added benefit, voltage reversal is eliminated in the ring topology, resulting in long lifetimes for energy-storage capacitors. System tests were performed using an adjustable inductive load at a voltage level of 3.3 kV, a peak current of 20 kA, and a current switching rate of 15 kA/micros.

Review of status developments of high-efficiency crystalline silicon solar cells

NASA Astrophysics Data System (ADS)

Liu, Jingjing; Yao, Yao; Xiao, Shaoqing; Gu, Xiaofeng

2018-03-01

In order to further improve cell efficiency and reduce cost in achieving grid parity, a large number of PV manufacturing companies, universities and research institutes have been devoted to a variety of low-cost and high-efficiency crystalline Si solar cells. In this article, the cell structures, characteristics and efficiency progresses of several types of high-efficiency crystalline Si solar cells that have been in small scale production or are promising in mass production are presented, including passivated emitter rear cell, tunnel oxide passivated contact solar cell, interdigitated back contact cell, heterojunction with intrinsic thin-layer cell, and heterojunction solar cells with interdigitated back contacts. Both the industrialization status and future development trend of high-efficiency crystalline silicon solar cells are also pinpointed.

Efficient High-Pressure State Equations

NASA Technical Reports Server (NTRS)

Harstad, Kenneth G.; Miller, Richard S.; Bellan, Josette

1997-01-01

A method is presented for a relatively accurate, noniterative, computationally efficient calculation of high-pressure fluid-mixture equations of state, especially targeted to gas turbines and rocket engines. Pressures above I bar and temperatures above 100 K are addressed The method is based on curve fitting an effective reference state relative to departure functions formed using the Peng-Robinson cubic state equation Fit parameters for H2, O2, N2, propane, methane, n-heptane, and methanol are given.

Highly Efficient, All-Dielectric Huygens Metasurfaces

NASA Astrophysics Data System (ADS)

Ollanik, Adam; Farrar-Foley, Nick; Smith, Jake; Escarra, Matthew

Demonstration of the control of light by the introduction of abrupt phase discontinuities across a subwavelength scale has opened the doors to a new level of wavefront control. All-dielectric Huygens metasurfaces hold significant promise due to their dramatically improved efficiency over plasmonic approaches. We present the successful design, computational modeling, and experimental realization of all-dielectric transmissive Huygens metasurfaces capable of deflection efficiency >90%. Dielectric Huygens sources, taking advantage of spectrally aligned electric and magnetic dipole resonances, are capable of tunable phase delay for transmitted light with near unity efficiency of forward scattering. Using ellipsoidal cylinder nanoantennas, we are able to manipulate the phase response and engineer a metasurface with a spatially gradient phase profile. Through careful design and optimization we mitigate the effects of inter-antenna coupling. We have designed and modeled metasurfaces demonstrating anomalous refraction with very high efficiency (>80%) for wavelength bands from the UV to the near-IR. These surfaces were designed using three distinct nanoantenna materials, Si, TiO2, and GaP, to demonstrate the flexibility of the technique. Experimentally, Si nanoantennas are fabricated using a combination of electron beam lithography and ICP/RIE-etching. Metasurfaces are characterized using a goniospectrometer capable of mapping light intensity on a cylindrical shell surrounding the metasurface.

An improvement in the calculation of the efficiency of oxidative phosphorylation and rate of energy dissipation in mitochondria

NASA Astrophysics Data System (ADS)

Ghafuri, Mohazabeh; Golfar, Bahareh; Nosrati, Mohsen; Hoseinkhani, Saman

2014-12-01

The process of ATP production is one of the most vital processes in living cells which happens with a high efficiency. Thermodynamic evaluation of this process and the factors involved in oxidative phosphorylation can provide a valuable guide for increasing the energy production efficiency in research and industry. Although energy transduction has been studied qualitatively in several researches, there are only few brief reviews based on mathematical models on this subject. In our previous work, we suggested a mathematical model for ATP production based on non-equilibrium thermodynamic principles. In the present study, based on the new discoveries on the respiratory chain of animal mitochondria, Golfar's model has been used to generate improved results for the efficiency of oxidative phosphorylation and the rate of energy loss. The results calculated from the modified coefficients for the proton pumps of the respiratory chain enzymes are closer to the experimental results and validate the model.

Highly Efficient Amplifier for Ka-Band Communications